AU1581500A - Development of novel anti-microbial agents based on bacteriophage genomics - Google Patents

Development of novel anti-microbial agents based on bacteriophage genomics Download PDF

Info

Publication number
AU1581500A
AU1581500A AU15815/00A AU1581500A AU1581500A AU 1581500 A AU1581500 A AU 1581500A AU 15815/00 A AU15815/00 A AU 15815/00A AU 1581500 A AU1581500 A AU 1581500A AU 1581500 A AU1581500 A AU 1581500A
Authority
AU
Australia
Prior art keywords
bacteriophage
target
sequence
phage
orf
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
AU15815/00A
Other versions
AU774841B2 (en
Inventor
Michael Dubow
Philippe Gros
Jerry Pelletier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Targanta Therapeutics Inc
Original Assignee
Targanta Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/407,804 external-priority patent/US6982153B1/en
Application filed by Targanta Therapeutics Inc filed Critical Targanta Therapeutics Inc
Publication of AU1581500A publication Critical patent/AU1581500A/en
Application granted granted Critical
Publication of AU774841B2 publication Critical patent/AU774841B2/en
Assigned to TARGANTA THERAPEUTICS INC. reassignment TARGANTA THERAPEUTICS INC. Request to Amend Deed and Register Assignors: PHAGETECH, INC.
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/18Testing for antimicrobial activity of a material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2795/00Bacteriophages
    • C12N2795/00011Details
    • C12N2795/10011Details dsDNA Bacteriophages
    • C12N2795/10022New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2795/00Bacteriophages
    • C12N2795/00011Details
    • C12N2795/10011Details dsDNA Bacteriophages
    • C12N2795/10041Use of virus, viral particle or viral elements as a vector
    • C12N2795/10043Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Peptides Or Proteins (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Description

WO 00/32825 PCT/IB99/02040 1 DESCRIPTION Development of Novel Anti-Microbial Agents Based on Bacteriophage Genomics 5 BACKGROUND OF THE INVENTION The present invention relates to the field of antibacterial agents and the treatment of infections of animals or other complex organisms by bacteria. 10 The frequency and spectrum of antibiotic-resistant infections have, in recent years, increased in both the hospital and community. Certain infections have become essentially untreatable and are growing to epidemic proportions in the developing world as well as in institutional settings in the developed world. The staggering spread of antibiotic resistance in pathogenic bacteria has been attributed to microbial 15 genetic characteristics, widespread use of antibiotic drugs, and changes in society that enhance the transmission of drug-resistant organisms. This spread of drug resistant microbes is leading to ever increasing morbidity, mortality and health-care costs. Ironically, it is the very success of antibiotics, resulting in their widespread use, that has contributed the most to rising numbers of drug resistant bacterial strains. 20 The longer a bacterial strain is exposed to a drug, the more likely it is to acquire resistance. Today, a total of 160 antibiotics, all based on a few basic chemical structures and targeting a small number of metabolic pathways, have found their way to market. Over-prescription of these drugs, as well as the failure of patients to comply with the complete antibiotic regimen, has lead to the rapid emergence of 25 antibiotic resistant strains. Such misuse of prescriptions, careless use of antibiotics in virtually all commercial production of beef and fowl, and changing societal conditions, such as the growth of day-care centers, increased long-term care in hospitals, and increased mobility of the population, has provided an environment where drug-resistant microbes can emerge and spread. Thus, virtually all common 30 infectious bacteria are becoming, or have already become, resistant to one or more groups of antibiotics. Such resistance now reaches all classes of antibiotics currently in use, including: P-lactams, fluoroquinolones, aminoglycosides, macrolide peptides, chloramphenicol, tetracyclines, rifampicin, folate inhibitors, glycopeptides, and mupirocin. 35 Over the last 45 years bacteria have adapted genetically to avoid the destruction/alteration of the essential pathways that these chemotherapeutic agents WO 00/32825 PCT/IB99/02040 2 target. Antibiotic resistant bacterial strains are now emerging at a higher rate than the rate at which new antibiotics are being developed. The consequence of this dilemma has been a dramatic increase in the cost of treating infections what would otherwise easily succumb to routine antibiotic therapy. Furthermore, and perhaps most 5 importantly, the emergence of multiple drug resistant pathogenic bacteria has led to a significant increase in morbidity and mortality, particularly in institutional settings. Most major pharmaceutical companies have on-going drug discovery programs for novel anti-microbials. These are based on screens for small molecule inhibitors (natural products, bacterial culture media, libraries of small molecules, 10 combinatorial chemistry) of crucial metabolic pathways of the micro-organism of interest (e.g., bacteria, fungi, parasites, worms). The screening process is largely for cytotoxic compounds and in most cases is not based on a known mechanism of action of the compounds. Pharmaceutical companies have large programs in this area. Classical drug screening programs are being exhausted and many of these 15 pharmaceutical companies are looking towards rational drug design programs. Several small to mid-size biotechnology companies as well as large pharmaceutical companies have developed systematic high-throughput sequencing programs to decipher the genetic code of specific micro-organisms of interest. The goal is to identify, through sequencing, unique biochemical pathways or intermediates 20 that are unique to the microorganism. Knowledge of this may, in turn, form the rationale for a drug discovery program based on the mechanism of action of the identified enzymes/proteins. Genome Therapeutics Corp., The Institute for Genome Research, Human Genome Sciences Inc., and other companies have such sequencing programs in place. However, one of the most critical steps in this approach is the 25 ascertainment that the identified proteins and biochemical pathways are 1) non redundant and essential for bacterial survival, and 2) constitute suitable and accessible targets for drug discovery.
WO 00/32825 PCT/IB99/02040 SUMMARY OF THE INVENTION While animals such as humans are, on occasion, infected by pathogenic bacteria, bacteria also have natural enemies. A number of host-specific viruses, 5 known as bacteriophages or phages, infect and kill bacteria in the natural environment. Such bacteriophages generally have small compact genomes and bacteria are their exclusive hosts. Many known bacteria are host to a large number of bacteriophages that have been described in the literature. During the 1940's - 1960's, phage biology was an area of active research. As a testimony to this, the study of 10 phages which infect and inhibit the enteric bacterium Escherichia coli (E. coli) contributed much to the early understanding of molecular biology and virology. As is generally understood, bacteriophage (or phages) are viruses that infect and kill bacteria. They are natural enemies of bacteria and, over the course of evolution, have developed proteins (products of DNA sequences) which enable them 15 to infect a host bacteria, replicate their genetic material, usurp host metabolism, and ultimately kill their host. The scientific literature well documents the fact that many known bacteria have a large number of such bacteriophages (Ackermann and DuBow, 1987) that can infect and kill them (for example, see the ATCC bacteriophage collection at http://www.atcc.org). 20 This invention utilizes the observation that bacteriophages successfully infect and inhibit or kill host bacteria, targeting a variety of normal host metabolic and physiological traits, some of which are shared by all bacteria, pathogenic and nonpathogenic alike. The term "pathogenic" as used herein denotes a contribution to or implication in disease or a morbid state of an infected organism. The invention 25 thus involves identifying and elucidating the molecular mechanisms by which phages interfere with host bacterial metabolism, an objective being to provide novel targets for drug design. Whether the phage blocks bacterial RNA transcription or translation, or attacks other important metabolic pathways, such as cell wall assembly or membrane integrity, the basic blueprint for a phage's bacteria-inhibiting ability is 30 encoded in its genome and can be unlocked using bioinformatics, functional genomics, and proteomics. By these means, the invention utilizes sequence information from the genomics of bacteriophage to identify novel antimicrobials that can be further used to actively and/or prophylactically treat bacterial infection. Two important components of the invention thus are: i) the identification of 35 bacteria-inhibiting phage open reading frames ("ORF"s) and corresponding products that can be used to develop antibiotics based on amino acid sequence and secondary structural characteristics of the ORF products, and ii) the use of bacteriophages to map WO 00/32825 PCT/IB99/02040 4 out essential bacterial target genes and homologs, which can in turn lead to the development of suitable anti-microbial agents. These two avenues represent new and general methods for developing novel antimicrobials. The invention thus concerns the identification of bacteriophage ORFs that 5 supply bacteria-inhibiting functions. In this regard, use of the terms "inhibit", "inhibition", "inhibitory", and "inhibitor" all refer to a function of reducing a biological activity or function. Such reduction in activity or function can, for example, be in connection with a cellular component, e.g., an enzyme, or in connection with a cellular process, e.g., synthesis of a particular protein, or in 10 connection with an overall process of a cell, e.g., cell growth. In reference to bacterial cell growth, for example, an inhibitory effect (i.e., a bacteria-inhibiting effect) may be bacteriocidal (killing of bacterial cells) or bacteriostatic (i.e., stopping or at least slowing bacterial cell growth). The latter slows or prevents cell growth such that fewer cells of the strain are produced relative to uninhibited cells over a given period 15 of time. From a molecular standpoint, such inhibition may equate with a reduction in the level of, or elimination of, the transcription and/or translation of a specific bacterial target(s), or reduction or elimination of activity of a particular target biomolecule. It is particularly advantageous to evaluate a plurality of different phage ORFs 20 for inhibitory activity that may be from one, but is preferably from a plurality of different phage. For example, evaluating ORFs from a number of different phage of the same bacterial host provides at least two advantages. One is that the multiple phages will provide identification of a variety of different targets. Second, it is likely that multiple phage will utilize the same cellular target 25 As used herein, the terms "bacteriophage" and "phage" are used interchangeably to refer to a virus which can infect a bacterial strain or a number of different bacterial strains. In the context of this invention, the term "bacteriophage ORF" or ""phage ORF" or similar term refers to a nucleotide sequence in or from a bacteriophage. In 30 connection with a particular ORF, the terms refer an open reading frame which has at least 95% sequence identity, preferably at least 97% sequence identity, more preferably at least 98% sequence identity with an ORF from the particular phage identified herein (e.g., with an ORF as identified herein) or to a nucleic acid sequence which has the specified sequence identify percentage with such an ORF sequence. 35 A first aspect of the invention thus provides a method for identifying a bacteriophage nucleic acid coding region encoding a product active on an essential bacterial target by identifying a nucleic acid sequence encoding a gene product which WO 00/32825 PCT/IB99/02040 5 provides a bacteria-inhibiting function when the bacteriophage infects a host bacterium, preferably one that is an animal or plant pathogen, more preferably a bird or mammalian pathogen, and most preferably a human pathogen. The bacteriophage is an uncharacterized bacteriophage. Thus, the method excludes, for example, phage 5 k, #x174, m13 and other E.coli-specific bacteriophage that have been studied with respect to gene number and/or function. It also excludes, for example, the nucleic acid coding regions described in Tables 12-14, and in preferred embodiments, excludes the phage in which those regions are naturally located. In connection with bacteriophage, the term "uncharacterized" means that a 10 certain bacteriophage's genome has not yet been fully identified such that the genes having function involved in inhibiting host cells have not been identified. In particular, phage for which the description of genomic or protein sequence was first provided herein are uncharacterized. Phage sequences for which host bacteria inhibiting functions have been identified prior to the filing of the present application 15 (or alternatively prior to the present invention) are specifically excluded from the aspects involving utilization of sequences from uncharacterized bacteriophage, except that aspects may involve a plurality of phage where one or more of those phage are uncharacterized and one or more others have been characterized to some extent. A number of different bacteria-inhibiting phage ORFs are indicated in Tables 11-14. 20 The phage ORFs or sequences identified therein are not within the term "uncharacterized; alternatively, in preferred embodiments the phage containing those ORFs are excluded from this term. Further, any additional phage ORFs (or alternatively the phage which contain those ORFs) which have previously been described in the art as bacteria-inhibiting ORFs are expressly excluded; those ORFs or 25 phage are known to those skilled in the art and the exclusion can be made express by specifically naming such ORFs or phage as needed (likewise for uncharacterized targets as described below). For the sake of brevity, such a listing is not expressly presented, as such information is readily available to those skilled in the art. Stating that an agent or compound is "active on" a particular cellular target, 30 such as the product of a particular gene, means that the target is an important part of a cellular pathway which includes that target and that the agent acts on that pathway. Thus, in some cases the agent may act on a component upstream or downstream of the stated target, including on a regulator of that pathway or a component of that pathway. By "essential", in connection with a gene or gene product, is meant that the host 35 cannot survive without, or is significantly growth compromised, in the abs-ence depletion, or alteration of functional product. An "essential gene" is thus one that encodes a product that is beneficial, or preferably necessary, for cellular growth in WO 00/32825 PCT/IB99/02040 6 vitro in a medium appropriate for growth of a strain having a wild-type allele corresponding to the particular gene in question. Therefore, if an essential gene is inactivated or inhibited, that cell will grow significantly more slowly, preferably less than 20%, more preferably less than 10%, most preferably less than 5% of the growth 5 rate of the uninhibited wild-type, or not at all, in the growth medium. Preferably, in the absence of activity provided by a product of the gene, the cell will not grow at all or will be non-viable, at least under culture conditions similar to the in vivo conditions normally encountered by the bacterial cell during an infection. For example, absence of the biological activity of certain enzymes involved in bacterial cell wall synthesis 10 can result in the lysis of cells under normal osmotic conditions, even though protoplasts can be maintained under controlled osmotic conditions. In the context of the invention, essential genes are generally the preferred targets of antimicrobial agents. Essential genes can encode target molecules directly or can encode a product involved in the production, modification, or maintenance of a target molecule. 15 A "target" refers to a biomolecule that can be acted on by an exogenous agent, thereby modulating, preferably inhibiting, growth or viability of a cell. In most cases such a target will be a nucleic acid sequence or molecule, or a polypeptide or protein. However, other types of biomolecules can also be targets, e.g., membrane lipids and cell wall structural components. 20 The term "bacterium" refers to a single bacterial strain, and includes a single cell, and a plurality or population of cells of that strain unless clearly indicated to the contrary. In reference to bacteria or bacteriophage, the term "strain" refers to bacteria or phage having a particular genetic content. The genetic content includes genomic content as well as recombinant vectors. Thus, for example, two otherwise identical 25 bacterial cells would represent different strains if each contained a vector, e.g., a plasmid, with different phage ORF inserts. In preferred embodiments, the phage is Staphylococcus aureus phage 77, 3A, 96, or 44 AHJD, Enterococcus sp. phage 182, or Streptococcus pneumoniae phage Dp-1. 30 In preferred embodiments, the phage is selected from. Preferred embodiments involve expressing at least one recombinant phage ORF(s) in a bacterial host followed by inhibition analysis of that host. Inhibition following expression of the phage ORF is indicative that the product of the ORF is active on an essential bacterial target. Such evaluation can be carried out in a variety of different formats, such as on a 35 support matrix such as a solidified medium in a petri dish, or in liquid culture.
WO 00/32825 PCT/IB99/02040 7 Preferably a plurality of phage ORFs are expressed in at least one bacterium. The plurality of phage ORFs can be from one or a plurality of phage. With respect to a single phage or at least one phage in a plurality of phages, the plurality of expressed ORFs preferably represents at least 10%, more preferably at least 20%, 40%, or 60%, 5 still more preferably at least 80% or 90%, and most preferably at least 95% of the ORFs in the phage genome. Preferably, for a plurality of phage, the plurality of expressed ORFs preferably represents at least 10%, more preferably at least 20%, 40%, or 60%, still more preferably at least 80% or 90%, and most preferably at least 95% of the ORFs in the phage genome of each phage. The plurality of phage ORFs 10 can be expressed in a single bacterium, or in a plurality of bacteria where one ORF is expressed in each bacterium, or in a plurality of bacteria where a plurality of ORFs are expressed in at least one or in all of the plurality of bacteria, or combinations of these. In embodiments of the above aspect (as well as in other aspects herein) in which a plurality of phage are utilized, a plurality of phage have the same bacterial 15 host species; have different bacterial host species; or both. The plurality of phage includes at least two different phage, preferably at least 3,4,5,6,8,10,15,20, or more different phage. Indeed, more preferably, the plurality of phage will include 50, 75, 100, or more phage. As described herein, the larger number of phage is useful to provide additional target and target evaluation information useful in developing 20 antibacterial agents, for example, by providing identification of a larger range of bacterial targets, and/or providing further indication of the suitability of a particular target (for example, utilization of a target by a number of different unrelated phage can suggest that the target is particularly stable and accessible and effective) and/or can indicate alternate sites on a target which interact with different inhibitors. 25 Further embodiments involve confirmation of the inhibitor function of the phage ORF, such as by utilizing or incorporating a control(s) designed to confirm the inhibitory nature of the ORF(s) being evaluated. The control can, for example, be provided by expression of an inactive or partially inactive form of the ORF or ORF product, and/or by the absence of expression of the ORF or ORF product in the same 30 or a closely comparable bacterial strain as that used for expression of the test ORF. The reduced level of activity or the absence of active ORF product in the control will thus not provide the inhibition provided by a corresponding inhibitory ORF, or will provide a distinguishably lower level of inhibition. An inactivated or partially inactivated control has a mutation(s), e.g., in the coding region or in flanking 35 regulatory elements, that reduce(s) or eliminate(s) the normal function of the ORF.7 Thus, the inhibition of a bacterium following expression of a phage ORF is determined by comparison with the effects of expression of an inactivated ORF or the WO 00/32825 PCT/IB99/02040 8 response of the bacteria in the absence of expression in the same or similar type bacterium. Such determination of inhibition of the bacterium following expression of the ORF is indicative of a bacteria-inhibiting function. These manipulations are routinely understood and accomplished by those of skill in the art using standard 5 techniques. In embodiments utilizing absence of expression of the ORF, the bacteria can, for example, contain an empty vector or a vector which allows expression of an unrelated sequence which is preferably non-inhibitory. Alternatively, the bacteria may have no vector at all. Combinations of such controls or other controls may also be utilized as recognized by those skilled in the art. 10 In embodiments involving expression of a phage ORF in a bacterial strain, in preferred embodiments that expression is inducible. By "inducible" is meant that expression is absent or occurs at a low level until the occurrence of an appropriate environmental stimulus provides otherwise. For the present invention such induction is preferably controlled by an artificial 15 environmental change, such as by contacting a bacterial strain population with an inducing compound (i.e., an inducer). However, induction could also occur, for example, in response to build-up of a compound produced by the bacteria in the bacterial culture, e.g., in the medium. As uncontrolled or constitutive expression of inhibitory ORFs can severely compromise bacteria to the point of eradication, such 20 expression is therefore undesirable in many cases because it would prevent effective evaluation of the strain and inhibitor being studied. For example, such uncontrolled expression could prevent any growth of the strain following insertion of a recombinant ORF, thus preventing determination of effective transfection or transformation. A controlled or inducible expression is therefore advantageous and is 25 generally provided through the provision of suitable regulatory elements, e.g., promoter/operator sequences that can be conveniently transcriptionally linked to a coding sequence to be evaluated. In most cases, the vector will also contain sequences suitable for efficient replication of the vector in the same or different host cells and/or sequences allowing selection of cells containing the vector, i.e., 30 "selectable markers." Further, preferred vectors include convenient primer sequences flanking the cloning region from which PCR and/or sequencing may be performed. As knowledge of the nucleotide sequence of phage ORFs is useful, e.g., for assisting in the identification of phage proteins active against essential bacterial host targets, preferred embodiments involve the sequencing of at least a portion of the 35 phage genome in combination with the above methods. This can be done either-efbre or after or independent of expression and inhibition of the ORF in the bacteria, and provides information on the nature and characteristics of the ORF. Such a portion is WO 00/32825 PCT/IB99/02040 9 preferably at least 10%, 20%, 40%, 80%, 90%, or 100% of the phage genome. For embodiments in which a plurality of phage are utilized, preferably each phage is sequenced to an extent as just specified. Such sequencing is preferably accompanied by computer sequence analysis to 5 define and evaluate ORF(s), ORF products, structural motifs or functional properties of ORF products, and/or their genetic control elements. Thus, certain embodiments incorporate computer sequence analyses or nucleic acid and/or amino acid sequences. Further, existing data banks can provide phage sequence and product information which can be utilized for analysis and identification of ORFs in the sequence. 10 Computer analysis may further employ known homologous sequences from other species that suggest or indicate conserved underlying biochemical function(s) for the inhibitory or potentially inhibitory ORF sequence(s) being evaluated. This can include the sequences of signature motifs of identified classes of inhibitors. In the context of the phage nucleic acid sequences, e.g., gene sequences, of this 15 invention, the terms "homolog" and "homologous" denote nucleotide sequences from different bacteria or phage strains or species or from other types of organisms that have significantly related nucleotide sequences, and consequently significantly related encoded gene products, preferably having related function. Homologous gene sequences or coding sequences have at least 70% sequence identity (as defined by the 20 maximal base match in a computer-generated alignment of two or more nucleic acid sequences) over at least one sequence window of 48 nucleotides, more preferably at least 80 or 85%, still more preferably at least 90%, and most preferably at least 95%. The polypeptide products of homologous genes have at least 35% amino acid sequence identity over at least one sequence window of 18 amino acid residues, more 25 preferably at least 40%, still more preferably at least 50% or 60%, and most preferably at least 70%, 80%, or 90%. Preferably, the homologous gene product is also a functional homolog, meaning that the homolog will functionally complement one or more biological activities of the product being compared. For nucleotide or amino acid sequence comparisons where a homology is defined by a % sequence 30 identity, the percentage is determined using BLAST programs ( with default parameters (Altschul et al., 1997, "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acid Res. 25:3389-3402). Any of a variety of algorithms known in the art which provide comparable results can also be used, preferably using default parameters. Performance characteristics for 35 three different algorithms in homology searching is described in Salamov et al, 1999, "Combining sensitive database searches with multiple intermediates to detect distant WO 00/32825 PCT/IB99/02040 10 homologues." Protein Eng. 12:95-100. Another exemplary program package is the GCGTM package from the University of Wisconsin. Homologs may also or in addition be characterized by the ability of two complementary nucleic acid strands to hybridize to each other under appropriately 5 stringent conditions. Hybridizations are typically and preferably conducted with probe-length nucleic acid molecules, preferably 20-100 nucleotides in length. Those skilled in the art understand how to estimate and adjust the stringency of hybridization conditions such that sequences having at least a desired level of complementarity will stably hybridize, while those having lower complementarity will not. For examples of 10 hybridization conditions and parameters, see, e.g.,. Maniatis, T. et al. (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor University Press, Cold Spring, N.Y.; Ausubel, F.M. et al. (1994) Current Protocols in Molecular Biologv. John Wiley & Sons, Secaucus, N.J. Homologs and homologous gene sequences may thus be identified using any nucleic acid sequence of interest, including the phage 15 ORFs and bacterial target genes of the present invention. A typical hybridization, for example, utilizes, besides the labeled probe of interest, a salt solution such as 6xSSC (NaCl and Sodium Citrate base) to stabilize nucleic acid strand interaction, a mild detergent such as 0.5% SDS, together with other typical additives such as Denhardt's solution and salmon sperm DNA. The 20 solution is added to the immobilized sequence to be probed and incubated at suitable temperatures to preferably permit specific binding while minimizing nonspecific binding. The temperature of the incubations and ensuing washes is critical to the success and clarity of the hybridization. Stringent conditions employ relatively higher temperatures, lower salt concentrations, and/or more detergent than do non-stringent 25 conditions. Hybridization temperatures also depend on the length, complementarity level, and nature (ie, "GC content") of the sequences to be tested. Typical stringent hybridizations and washes are conducted at temperatures of at least 40'C, while lower stringency hybridizations and washes are typically conducted at 37*C down to room temperature (-25 0 C). One of skill in the art is aware that these conditions may vary 30 according to the parameters indicated above, and that certain additives such as formamide and dextran sulphate may also be added to affect the conditions. By "stringent hybridization conditions" is meant hybridization conditions at least as stringent as the following: hybridization in 50% formamide, 5X SSC, 50 mM NaH 2
PO
4 , pH 6.8, 0.5% SDS, 0.1 mg/mL sonicated salmon sperm DNA, and 5X 35 Denhart's solution at 42*C overnight; washing with 2X SSC, 0.1% SDS at 45'G; and washing with 0.2X SSC, 0.1% SDS at 45*C.
WO 00/32825 PCT/IB99/02040 In sequence comparison analyses, an ORF, or motif, or set of motifs in a bacteriophage sequence can be compared to known inhibitor sequences, e.g., homologous sequences encoding homologous inhibitors of bacterial function. Likewise, the analysis can include comparison with the structure of essential bacterial 5 gene products, as structural similarities can be indicative of similar or replacement biological function. Such analysis can include the identification of a signature, or characteristic motifs) of an inhibitor or inhibitor class. Also, the identification of structural motifs in an encoded product, based on nucleotide or amino acid sequence analysis, can be used to infer a biochemical 10 function for the product. A database containing identified structural motifs in a large number of sequences is available for identification of motifs in phage sequences. The database is PROSITE, which is available at www.expasy.ch/cgi-bin/scanprosite. The identification of motifs can, for example, include the identification of signature motifs for a class or classes of inhibitory proteins. Other such databases may also be used. 15 In aspects and preferred embodiments described herein, in which a bacterium or host bacterium is specified, the bacterium or host bacterium is preferably selected from a pathogenic bacterial species, for example, one selected from Table 1. Preferably, an animal or plant pathogen is used. For animals, preferably the bacterium is a bird or mammalian pathogen, still more preferably a human pathogen. 20 In aspects and preferred embodiments involving a bacteriophage or sequences from a bacteriophage, one or more bacteriophage are preferably selected from those listed in Table 1. Those exemplary bacteriophge are readily obtained from the indicated sources. In some cases, it is advantageous to utilize phage with non-pathogenic host 25 bacteria. The genome, structural motif, ORF, homolog, and other analyses described herein can be performed on such phage and bacteria. Such analysis provides useful information and compositions. The results of such analyses can also be utilized in aspects of the present invention to identify homologous ORFs, especially inhibitor ORFs in phage with pathogenic bacterial hosts. Similarly, identification of a target in 30 a non-pathogenic host can be used to identify homologous sequences and targets in pathogenic bacteria, especially in genetically closely related bacteria. Those skilled in the art are familiar with bacterial genetic relationships and with how to determine relatedness based on levels of genomic identity or other measures of nucleotide sequence and/or amino acid sequence similarity, and/or other physical and culture 35 characteristics such as morphology, nutritional requirements, or minimal media-4o support growth.
WO 00/32825 PCT/IB99/02040 12 Also in preferred embodiments, an embodiments of this aspect is combined with an embodiment of the following aspect. A related aspect of the invention provides methods for identifying a target for antibacterial agents by identifying the bacterial target(s) of at least one 5 uncharacterized or untargeted inhibitor protein or RNA from a bacteriophage. Such identification allows the development of antibacterial agents active on such targets. Preferred embodiments for identifying such targets involve the identification of binding of target and phage ORF products to one another. The phage ORF products may be subportions of a larger ORF product that also binds the host target. In 10 preferred embodiments, the phage protein or RNA is from an uncharacterized bacteriophage in Table 1. This aspect preferably includes the identification of a plurality of such targets in one or a plurality of different bacteria, preferably in one or a plurality of bacteria listed in Table 1. In preferred embodiments of this aspect and other aspects of this invention 15 involving particular phage ORIs or phage sequences, the ORF is Staphylococcus aureus phage 77 ORF 17, 19, 43, 102, 104, or 182 as identified in U.S. application 09/407,804, S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014. 20 As indicated for the above aspect, preferably the method involves the use of a plurality of different phage, and thus a plurality of different phage inhibitors and/or inhibitor ORFs. In addition to uncharacteized phage ORF products, it is also useful to identify the targets of phage ORF products which are known to be inhibitors of host bacteria, 25 but where the target has not been identified. Thus, such inhibitors can likewise be utilized as "untargeted" inhibitor phage ORFs and ORF products, e.g., proteins or RNAs. In the context of inhibitor proteins or RNAs from a phage, the term "uncharacterized" means that a bacteria-inhibiting function for the protein has not 30 previously been identified. Preferably, but not necessarily, the sequence of the protein or the corresponding coding region or ORF was not described in the art before the filing of the present application for patent (or alternatively prior to the present invention). Thus, this term specifically excludes any bacteria-inhibiting phage protein and its associated bacterial target which has been identified as inhibitory before the 35 present invention or alternatively before the filing of the present application, for example those identified in Tables 12-14 or otherwise identified herein. For example, from E. coli, phage T7 genes 0.7 and 2.0 target the host RNA polymerase, phage T4 WO 00/32825 PCT/IB99/02040 13 gp55/gp33 alter the specificity of host RNA polymerase. The T4 regB gene product also targets the host translation apparatus. As with the uncharacterized bacteriophage ORFs or bacteriophage above, for such identified proteins, the sequences encoding those proteins are excluded from the uncharacterized inhibitor proteins. 5 The term "fragment" refers to a portion of a larger molecule or assembly. For proteins, the term "fragment" refers to a molecule which includes at least 5 contiguous amino acids from the reference polypeptide or protein, preferably at least 8, 10, 12, 15, 20, 30, 50 or more contiguous amino acids. In connection with oligo- or polynucleotides, the term "fragment" refers to a molecule which includes at least 15 10 contiguous nucleotides from a reference polynucleotide, preferably at least 24, 30, 36, 45, 60, 90, 150, or more contiguous nucleotides. Preferred embodiments involve identification of binding that include methods for distinguishing bound molecules, for example, affinity chromatography, immunoprecipitation, crosslinking, and/or genetic screen methods that permit 15 protein:protein interactions to be monitored. One of skill in the art is familiar with these techniques and common materials utilized (see, e.g., Coligan, J. et al. (eds.) (1995) Current Protocols in Protein Science, John Wiley & Sons, Secaucus, N.J.). Genetic screening for the identification of protein:protein interactions typically involves the co-introduction of both a chimeric bait nucleic acid sequence (here, the 20 phage ORF to be tested) and a chimeric target nucleic acid sequence that, when co expressed and having affinity for one another in a host cell, stimulate reporter gene expression to indicate the relationship. A "positive" can thus suggest a potential inhibitory effect in bacteria. This is discussed in further detail in the Detailed Description section below. In this way, new bacterial targets can be identified that are 25 inhibited by specific phage ORF products or derivatives, fragments, mimetics, or other molecules. Other embodiments involve the identification and/or utilization of mutant targets by virtue of their host's relatively unresponsive nature in the presence of expression of ORFs previously identified as inhibitory to the non-mutant or wild-type 30 strain. Such mutants have the effect of protecting the host from an inhibition that would otherwise occur and indirectly allow identification of the precise responsible target for follow-up studies and anti-microbial development. In certain embodiments, rescue from inhibition occurs under conditions in which a bacterial target or mutant target is highly expressed. This is performed, for example, through coupling of the 35 sequence with regulatory element promoters, e.g., as known in the art, which regulate expression at levels higher than wild-type, e.g., at a level sufficiently higher that the WO 00/32825 PCT/IB99/02040 14 inhibitor can be competitively bound to the highly expressed target such that the bacterium is detectably less inhibited. Identification of the bacterial target can involve identification of a phage specific site of action. This can involve a newly identified target, or a target where the 5 phage site of action differs from the site of action of a previously known antibacterial agent or inhibitor. For example, phage T7 genes 0.7 and 2.0 target the host RNA polymerase, which is also the cellular target for the antibacterial agent, rifampin. To the extent that a phage product is found to act at a different site than previously described inhibitors, aspects of the present invention can utilize those new, phage 10 specific sites for identification and use of new agents. The site of action can be identified by techniques well-known to those skilled in the art, for example, by mutational analysis, binding competition analysis, and/or other appropriate techniques. Once a bacterial host target protein or nucleic acid or mutant target sequence 15 has been identified and/or isolated, it too can be conveniently sequenced, sequence analyzed (e.g., by computer), and the underlying gene(s), and corresponding translated product(s) further characterized. Preferred embodiments include such analysis and identification. Preferably such a target has not previously been identified as an appropriate target for antibacterial action. 20 Certain embodiments include the identification of at least one inhibitory phage ORF or ORF product, e.g., as described for the above aspect, and thus are a combination of the two aspects. Additionally, the invention provides methods for identifying targets for antibacterial agents by identifying homologs of a bacterial target e.g., S. aureus, 25 Enterococcusfaecalis or other Enterococci, and Streptococcus pneumoniae of a bacteriophage inhibitory ORF product. Such homologs may be utilized in the various aspects and embodiments described herein as describded for the host Enterococcus sp. for bacteriophage 182. Other aspects of the invention provide isolated, purified, or enriched specific 30 phage nucleic acid and amino acid sequences, subsequences, and homologs thereof for phage selected from uncharacterized phage listed in Table 1, preferably from bacteriophage 77, 3A, 96, 44AHJD (Staphylococcus aureus host bacterium), Dp-1 (Streptococcus pneumoniae host), or 182 (Enterococcus host) or other phage listed in Table 1 for those bacteria. For example, such sequences do not include sequences 35 identified in any of Tables 11-14. Nucleotide sequences of this aspect are at least 15 nucleotides in length, preferably at least 18, 21, 24, or 27 nucleotides in length, more preferably at least 30, 50, or 90 nucleotides in length. In certain embodiments, longer WO 00/32825 PCT/IB99/02040 15 nucleic acids are preferred, for example those of at least 120, 150, 200, 300, 600, 900 or more nucleotides. Such sequences can, for example, be amplification oligonucleotides (e.g., PCR primers), oligonucleotide probes, sequences encoding a portion or all of a phage-encoded protein, or a fragment or all of a phage-encoded 5 protein. In preferred embodiments, the nucleic acid sequence contains a sequence which is within a length range with a lower length as specified above, and an upper length limit which is no more than 50, 60, 70, 80, or 90% of the length of the corresponding full-length ORF. The upper length limit can also be expressed in terms of the number of base pairs of the ORF (coding region). In preferred embodiments, 10 the nucleic acid sequence is from Staphylococcus aureus phage 77 ORF 17, 19, 43, 102, 104, or 182 as identified in U.S. application 09/407,804, S. aureus phage 44 AHJD ORF 1, 9, or 12, Streptococcus pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014. 15 As it is recognized that alternate codons will encode the same amino acid for most amino acids due to the degeneracy of the genetic code, the sequences of this aspect includes nucleic acid sequences utilizing such alternate codon usage for one or more codons of a coding sequence. For example, all four nucleic acid sequences GCT, GCC, GCA, and GCG encode the amino acid, alanine. Therefore, if for an 20 amino acid there exists an average of three codons, a polypeptide of 100 amino acids in length will, on average, be encoded by 3 10, or 5 x 1041 , nucleic acid sequences. Thus, a nucleic acid sequence can be modified (e.g., a nucleic acid sequence from a phage as specified above) to form a second nucleic acid sequence encoding the same polypeptide as encoded by the first nucleic acid sequence using routine procedures 25 and without undue experimentation. Thus, all possible nucleic acid sequences that encode the specified amino acid sequences are also fully described herein, as if all were written out in full, taking into account the codon usage, especially that preferred in the host bacterium. The alternate codon descriptions are available in common texbooks, for example, Stryer, BIOCHEMISTRY 3rd ed., and Lehninger, 30 BIOCHEMISTRY 3 rd ed., along wth many others. Codon preference tables for various types of organisms are available in the literature. Sequences with alternate codons at one or more sites can also be utilized in the computer-related aspects and embodiments herein. Because of the number of sequence variations involving alternate codon usage, for the sake of brevity, individual sequences are not separately 35 listed herein. Instead the alternate sequences are described by reference to the natural sequence with replacement of one or more (up to all e.g., up to 3, 5, 10, 15, 20, 30, 40, 50, or more) of the degenerate codons with alternate codons from the alternate codon WO 00/32825 PCT/IB99/02040 16 table (Table 6), or a modified table applicable to a particular organism that has differing codon usage, preferably with selection according to preferred codon usage for the normal host organism or a host organism in which a sequence is intended to be expressed. Those skilled in the art also understand how to alter the alternate codons to 5 be used for expression in organisms where certain codons code differently than shown in the "universal" codon table. For amino acid sequences or polypeptides, sequences contain at least 5 peptide linked amino acid residues, and preferably at least 6, 7, 10, 15, 20, 30, or 40, amino acids having identical amino acid sequence as the same number of contiguous amino 10 acid residues in a particular phage ORF product. In some cases longer sequences may be preferred, for example, those of at least 50, 60, 70, 80, or 100 amino acids in length. In preferred embodiments, the amino acid sequence contains a sequence which is within a length range with a lower length as specified above, and an upper length limit which is no more than 50, 60, 70, 80, or 90% of the length of the corresponding 15 full-length ORF product. The upper length limit can also be expressed in terms of the number of amino acid residues of the ORF product. In preferred embodiments, the amino acid sequence or polypeptide has bacteria-inhibiting function when expressed or otherwise present in a bacterial cell which is a host for the bacteriophage from which the sequence was derived. 20 By "isolated" in reference to a nucleic acid is meant that a naturally occurring sequence has been removed from its normal cellular (e.g., chromosomal) environment or is synthesized in a non-natural environment (e.g., artificially synthesized). Thus, the sequence may be in a cell-free solution or placed in a different cellular environment. The term does not imply that the sequence is the only nucleotide chain 25 present, but that it is essentially free (about 90-95% pure at least) of non-nucleotide material naturally associated with it, and thus is distinguished from isolated chromosomes. The term "enriched" means that the specific DNA or RNA sequence constitutes a significantly higher fraction (2-5 fold) of the total DNA or RNA present 30 in the cells or solution of interest than in normal or diseased cells or in cells from which the sequence was originally taken. This could be caused by a person by preferential reduction in the amount of other DNA or RNA present, or by a preferential increase in the amount of the specific DNA or RNA sequence, or by a combination of the two. However, it should be noted that enriched does not imply 35 that there are no other DNA or RNA sequences present, just that the relative ameurt~ of the sequence of interest has been significantly increased.
WO 00/32825 PCT/IB99/02040 17 The term "significant" is used to indicate that the level of increase is useful to the person making such an increase and an increase relative to other nucleic acids of about at least 2-fold, more preferably at least 5- to 10-fold or even more. The term also does not imply that there is no DNA or RNA from other sources. The other 5 source DNA may, for example, comprise DNA from a yeast or bacterial genome, or a cloning vector such as pUC19. This term distinguishes from naturally occurring events, such as viral infection, or tumor type growths, in which the level of one mRNA may be naturally increased relative to other species of mRNA. That is, the term is meant to cover only those situations in which a person has intervened to 10 elevate the proportion of the desired nucleic acid. It is also advantageous for some purposes that a nucleotide sequence be in purified form. The term "purified" in reference to nucleic acid does not require absolute purity (such as a homogeneous preparation). Instead, it represents an indication that the sequence is relatively more pure than in the natural environment 15 (compared to the natural level, this level should be at least 2-5 fold greater, e.g., in terms of mg/mL). Individual clones isolated from a cDNA library may be purified to electrophoretic homogeneity. The claimed DNA molecules obtained from these clones could be obtained directly from total DNA or from total RNA. The cDNA clones are not naturally occurring, but rather are preferably obtained via manipulation 20 of a partially purified naturally occurring substance (messenger RNA). The construction of a cDNA library from mRNA involves the creation of a synthetic substance (cDNA) and pure individual cDNA clones can be isolated from the synthetic library by clonal selection of the cells carrying the cDNA library. Thus, the process which includes the construction of a cDNA library from mRNA and isolation 25 of distinct cDNA clones yields an approximately 10 6 -fold purification of the native message. Thus, purification of at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. The terms "isolated", "enriched", and "purified" as respect nucleic acids, 30 above, may similarly be used to denote the relative purity and abundance of polypeptides ( multimers of amino acids joined one to another by c-carboxyl:a-amino group (peptide) bonds). These, too, may be stored in, grown in, screened in, and selected from libraries using biochemical techniques familiar in the art. Such polypeptides may be natural, synthetic or chimeric and may be extracted using any of 35 a variety of methods, such as antibody immunoprecipitation, other "tagging" techniques, conventional chromatography and/or electrophoretic methods. Some of the above utilize the corresponding nucleic acid sequence.
WO 00/32825 PCT/IB99/02040 18 As indicated above, aspects and embodiments of the invention are not limited to entire genes and proteins. The invention also provides and utilizes fragments and portions thereof, preferably those which are "active" in the inhibitory sense described above. Such peptides or oligopeptides and oligo or polynucleotides have preferred 5 lengths as specified above for nucleic acid and amino acid sequences from phage; corresponding recombinant constructs can be made to express the encoded same. Also included are homologous sequences and fragments thereof. Nucleic acid sequences of the present invention can be isolated using a method similar to those described herein or other methods known to those skilled in the art. 10 In addition, such nucleic acid sequences can be chemically synthesized by well known methods. Also, by having particular phage ORFs, e.g., the phage ORFs identified herein (e.g., anti-bacterial ORFs of the present invention, portions thereof, or oligonucleotides derived therefrom as described), other antimicrobial sequences from other bacteriophage sources can be identified and isolated using methods 15 described here or other methods, including methods utilizing nucleic acid hybridization and/or computer-based sequence alignment methods. The invention also provides bacteriophage antimicrobial DNA segments from other phages based on nucleic acids and sequences hybridizing to the presently identified inhibitory ORF under high stringency conditions or sequences that are 20 highly homologous. The bacteriophage segment from a specific phage, e.g., an antimicrobial DNA segment, can be used to identify a related segment from another unrelated phage based on stringent conditions of hybridization or on being a homolog based on nucleic acid and/or amino acid sequence comparisons. As with identified inhibitory sequences, such homologous coding sequences and products can be used as 25 antimicrobials, to construct active portions or derivatives, to construct peptidomimetics, and to identify bacterial targets. The nucleotide and amino acid sequences identified herein are believed to be correct, however, certain sequences may contain a small percentage of errors, e.g., 1 5%. In the event that any of the sequences have errors, the corrected sequences can be 30 readily provided by one skilled in the art using routine methods. For example, the nucleotide sequences can be confirmed or corrected by obtaining and culturing the relevant phage, and purifying phage genomic nucleic acids. A region or regions interest can be amplified, e.g., by PCR from the appropriate genomic template-using primers based on the described sequence. The amplified regions can then be 35 sequenced using any of the available methods (e.g., a dideoxy termination method).
WO 00/32825 PCT/IB99/02040 19 This can be done redundantly to provide the corrected sequence or to confirm that the described sequence is correct. Alternatively, a particular sequence or sequences can be identified and isolated as an insert or inserts in a phage genomic library and isolated, amplified, and sequenced by standard methods. Confirmation or correction 5 of a nucleotide sequence for a phage gene provides an amino acid sequence of the encoded product by merely reading off the amino acid sequence according to the normal codon relationships and/or expressed in a standard expression system and the polypeptide product sequenced by standard techniques. The sequences described herein thus provide unique identification of the corresponding genes, coding 10 sequences, and other sequences, allowing those sequences to be used in the various aspects of the present invention. In other aspects, the invention provides recombinant vectors and cells harboring at least one of the phage ORFs or portion thereof, or bacterial target sequences described herein. As understood by those skilled in the art, vectors may be 15 provided in different forms, including, for example, plasmids, cosmids, and virus based vectors. See, e.g., Maniatis, T. et al. (1989} Molecular Cloning: A Laboratory Manual, Cold Spring Harbor University Press, Cold Spring, N.Y.; See also, Ausubel, F.M. et al. (eds.) (1994) Current Protocols in Molecular Biologv. John Wiley & Sons, Secaucus, N.J. 20 In preferred embodiments, the vectors will be expression vectors, preferably shuttle vectors that permit cloning, replication, and expression within bacteria. An "expression vector" is one having regulatory nucleotide sequences containing transcriptional and translational regulatory information that controls expression of the nucleotide sequence in a host cell. Preferably the vector is constructed to allow 25 amplification from vector sequences flanking an insert locus. In certain embodiments, the expression vectors may additionally or alternativley support expression, and/or replication in animal, plant and/or yeast cells due to the presence of suitable regulatory sequences, e.g., promoters, enhancers, 3' stabilizing sequences, primer sequences, etc. In preferred embodiments, the promoters are inducible and specific 30 for the system in which expression is desired, e.g., bacteria, animal, plant, or yeast. The vectors may optionally encode a "tag" sequence or sequences to facilitate protein purification. Convenient restriction enzyme cloning sites and suitable selective marker(s) are also optionally included. Such selective markers can be, for example, antibiotic resistance markers or markers which supply an essential nutritive growth 35 factor to an otherwise deficient mutant host, e.g., tryptophan, histidine, or leucjneIn the Yeast Two-Hybrid systems described below.
WO 00/32825 PCT/IB99/02040 20 The term "recombinant vector" relates to a single- or double-stranded circular nucleic acid molecule that can be transfected into cells and replicated within or independently of a cell genome. A circular double-stranded nucleic acid molecule can be cut and thereby linearized upon treatment with appropriate restriction enzymes. An 5 assortment of nucleic acid vectors, restriction enzymes, and the knowledge of the nucleotide sequences cut by restriction enzymes are readily available to those skilled in the art. A nucleic acid molecule encoding a desired product can be inserted into a vector by cutting the vector with restriction enzymes and ligating the two pieces together. Preferably the vector is an expression vector, e.g., a shuttle expression 10 vector as described above. By " recombinant cell" is meant a cell possessing introduced or engineered nucleic acid sequences, e.g., as described above. The sequence may be in the form of or part of a vector or may be integrated into the host cell genome. Preferably the cell is a bacterial cell. 15 In another aspect, the invention also provides methods for identifying and/or screening compounds "active on" at least one bacterial target of a bacteriophage inhibitor protein or RNA. Preferred embodiments involve contacting such a bacterial target or targets (e.g., bacterial target proteins) with a test compound, and determining whether the compound binds to or reduces the level of activity of the bacterial target 20 (e.g., a bacterial target protein). Preferably this is done either in vivo (i.e., in a cell based assay) or in vitro, e.g., in a cell-free system under approximately physiological conditions. The compounds that can be used may be large or small, synthetic or natural, organic or inorganic, proteinaceous or non-proteinaceous. In preferred embodiments, 25 the compound is a peptidomimetic, as described herein, a bacteriophage inhibitor protein or fragment or derivative thereof, preferably an "active portion", or a small molecule. In preferred embodiments, the bacterial target is a target of a phage ORF identified herein, e.g., S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus 30 pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014. In particular embodiments, the methods include the identification of bacterial targets or the site of action of an inhibitor on a bacterial target as described above or otherwise described herein. 35 In embodiments involving binding assays, preferably binding is to a fragmeit or portion of a bacterial target protein, where the fragment includes less than 90%, 80%, 70%, 60%, 50%, 40%, or 30% of an intact bacterial target protein. Preferably, WO 00/32825 PCT/IB99/02040 21 the at least one bacterial target includes a plurality of different targets of bacteriophage inhibitor proteins, preferably a plurality of different targets. The plurality of targets can be in or from a plurality of different bacteria, but preferably is from a single bacterial species. 5 A "method of screening" refers to a method for evaluating a relevant activity or property of a large plurality of compounds (e.g., a bacteria-inhibiting activity), rather than just one or a few compounds. For example, a method of screening can be used to conveniently test at least 100, more preferably at least 1000, still more preferably at least 10,000, and most preferably at least 100,000 different compounds, 10 or even more. In the context of this invention, the term "small molecule" refers to compounds having molecular mass of less than 2000 Daltons, preferably less than 1500, still more preferably less than 1000, and most preferably less than 600 Daltons. Preferably but not necessarily, a small molecule is not an oligopeptide. 15 In a related aspect or in preferred embodiments, the invention provides a method of screening for potential antibacterial agents by determining whether any of a plurality of compounds, preferably a plurality of small molecules, is active on at least one target of a bacteriophage inhibitor protein or RNA. Preferred embodiments include those described for the above aspect, including embodiments which involve 20 determining whether one or more test compounds bind to or reduce the level of activity of a bacterial target, and embodiments which utilize a plurality of different targets as described above. The identification of bacteria-inhibiting phage ORFs and their encoded products also provides a method for identifying an active portion of such an encoded 25 product. This also provides a method for identifying a potential antibacterial agent by identifying such an active portion of a phage ORF or ORF product. In preferred embodiments, the identification of an active portion involves one or more of mutational analysis, deletion analysis, or analysis of fragments of such products. The method can also include determination of a 3-dimensional structure of an active 30 portion, such as by analysis of crystal diffraction patterns. In further embodiments, the method involves constructing or synthesizing a peptidomimetic compound, where the structure of the peptidomimetic compound corresponds to the structure of the active portion. In this context, "corresponds" means that the peptidomimetic compound structure has sufficient similarities to the structure of the active portion that 35 the peptidomimetic will interact with the same molecule as the phage protein and" preferably will elicit at least one cellular response in common which relates to the inhibition of the cell by the phage protein.
WO 00/32825 PCT/IB99/02040 22 In preferred embodiments, the ORF or ORF product is or is derived or obtained from S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus pneumoniae phage Dp-1 ORF 001, 00 2 , 0 04 , 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014 or product thereof. 5 The methods for identifying or screening for compounds or agents active on a bacterial target of a phage-encoded inhibitor can also involve identification of a phage-specific site of action on the target. Preferably in the methods for identifying or screening for compounds active on such a bacterial target, the target is uncharacterized; the target is from an 10 uncharacterized bacterium from Table 1; the site of action is a phage-specfic site of action. Further embodiments include the identification of inhibitor phage ORFs and bacterial targets as in aspects above. An "active portion" as used herein denotes an epitope, a catalytic or regulatory 15 domain, or a fragment of a bacteriophage inhibitor protein that is responsible for, or a significant factor in, bacterial target inhibition. The active portion preferably may be removed from its contiguous sequences and, in isolation, still effect inhibition. By "mimetic" is meant a compound structurally and functionally related to a reference compound that can be natural, synthetic, or chimeric. In terms of the present 20 invention, a "peptidomimetic," for example, is a compound that mimics the activity related aspects of the 3-dimensional structure of a peptide or polyeptide in a non peptide compound, for example mimics the structure of a peptide or active portion of a phage- or bacterial ORF-encoded polypeptide. A related aspect provides a method for inhibiting a bacterial cell by contacting 25 the bacterial cell with a compound active on a bacterial target of a bacteriophage inhibitor protein or RNA, where the target was uncharacterized. In preferred embodiments, the compound is such a protein, or a fragment or derivative thereof; a structural mimetic, e.g., a peptidomimetic, of such a protein or fragment; a small molecule; the contacting is performed in vitro, the contacting is performed in vivo in 30 an infected or at risk organism, e.g., an animal such as a mammal or bird, for example, a human, or other mammal described herein; the bacterium is selected from a genus and/or species listed in Table 1; the bacteriophage inhibitor protein is uncharacterized; the bacteriophage inhibitor protein is from an uncharacterized phage listed in Table 1; the phage inhibitor protein is from one of S. aureus phage 44AHJD ORF 1, 9, or 12, 35 Streptococcus pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016,01, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014.
WO 00/32825 PCT/IB99/02040 23 In the context of targets in this invention, the term "uncharacterized" means that the target was not recognized as an appropriate target for an antibacterial agent prior to the filing of the present application or alternatively prior to the present invention. Such lack of recognition can include, for example, situations where the 5 target and/or a nucleotide sequence encoding the target were unknown, situations where the target was known, but where it had not been identified as an appropriate target or as an essential cellular component, and situations where the target was known as essential but had not been recognized as an appropriate target due to a belief that the target would be inaccessible or otherwise that contacting the cell with a 10 compound active on the target in vitro would be ineffective in cellular inhibition, or ineffective in treatment of an infection. Methods described herein utilizing bacterial targets, e.g., for inhibiting bacteria or treating bacterial infections, can also utilize "uncharacterized target sites", meaning that the target has been previously recognized as an appropriate target for an antibacterial agent, but where an agent or inhibitor of 15 the invention is used which acts at a different site than that at which the previously utilized antibacterial agent, i.e., a phage-specific site. Preferably the phage-specific site has different functional characteristics from the previously utilized site. In the context of targets or target sites, the term "phage-specific" indicates that the target or site is utilized by at least one bacteriophage as an inhibitory target and is different 20 from previously identified targets or target sites. In the context of this invention, the term "bacteriophage inhibitor protein" refers to a protein encoded by a bacteriophage nucleic acid sequence which inhibits bacterial function in a host bacterium. Thus, it is a bacteria-inhibiting phage product. In the context of this invention, the phrase "contacting the bacterial cell with a 25 compound active on a bacterial target of a bacteriophage inhibitor protein" or equivalent phrases refer to contacting with an isolated, purified, or enriched compound or a composition including such a compound, but specifically does not rely on contacting the bacterial cell with an intact phage which encodes the compound. Preferably no intact phage are involved in the contacting. 30 Related aspects provide methods for prophylactic or therapeutic treatment of a bacterial infection by administering to an infected, challenged or at risk organism a therapeutically or prophylactically effective amount of a compound active on a target of a bacteriophage inhibitor protein or RNA, or as described for the previous aspect. Preferably the bacterium involved in the infection or risk of infection produces the 35 identified target of the bacteriophage inhibitor protein or alternatively produces-a homologous target compound. In preferred embodiments, the host organism is a plant or animal, preferably a mammal or bird, and more preferably, a human or other WO 00/32825 PCT/IB99/02040 24 mammal described herein. Preferred embodiments include, without limitation, those as described for the preceding aspect. Compounds useful for the methods of inhibiting, methods of treating, and pharmaceutical compositions can include novel compounds, but can also include 5 compounds which had previously been identified for a purpose other than inhibition of bacteria. Such compounds can be utilized as described and can be included in pharmaceutical compositions. In preferred embodiments of this and other aspects of the invention utilizing bacterial target sequences of a bacteriophage inhibitory ORF product, the target 10 sequence is encoded by a Staphylococcus nucleic acid coding sequence, preferably S. aureus, a Streptococcus nucleic acid coding sequence, preferably Streptococcus pneumoniae, or Enterococcus nucleic acid coding sequence. Possible target sequences are described herein by reference to sequence source sites. The amino acid sequence of a polypeptide target is readily provided by 15 translating the corresponding coding region. For the sake of brevity, the sequences are not reproduced herein. For the sake of brevity, the sequences are described by reference to the GenBank entries instead of being written out in full herein. In cases where the TIGR or GenBank entry for a coding region is not complete, the complete sequence can be readily obtained by routine methods, e.g., by isolating a clone in a 20 phage host genomic library, and sequencing the clone insert to provide the relevant coding region. The boundaries of the coding region can be identified by conventional sequence analysis and/or by expression in a bacterium in which the endogenous copy of the coding region has been inactivated and using subcloning to identify the functional start and stop codons for the coding region. 25 In the context of nucleic acid or amino acid sequences of this invention, the term "corresponding" indicates that the sequence is at least 95% identical, preferably at least 97% identical, and more preferably at least 99% identical to a sequence from the specified phage genome, a ribonucleotide equivalent, a degenerate equivalent (utilizing one or more degenerate codons), or a homologous sequence, where the 30 homolog provides functionally equivalent biological function. By "treatment" or "treating" is meant administering a compound or pharmaceutical composition for prophylactic and/or therapeutic purposes. The term "prophylactic treatment" refers to treating a patient or animal that is not yet infected but is susceptible to or otherwise at risk of a bacterial infection. The term "therapeutic 35 treatment" refers to administering treatment to a patient already suffering from infection.
WO 00/32825 PCT/IB99/02040 25 The term "bacterial infection" refers to the invasion of the host organism, animal or plant, by pathogenic bacteria. This includes the excessive growth of bacteria which are normally present in or on the body of the organism, but more generally, a bacterial infection can be any situation in which the presence of a bacterial 5 population(s) is damaging to a host organism. Thus, for example, an organism suffers from a bacterial population when excessive numbers of a bacterial population are present in or on the organism's body, or when the effects of the presence of a bacterial population(s) is damaging to the cells, tissue, or organs of the organism. The terms "administer", "administering", and "administration" refer to a 10 method of giving a dosage of a compound or composition, e.g., an antibacterial pharmaceutical composition, to an organism. Where the organism is a mammal, the method is, e.g., topical, oral, intravenous, transdermal, intraperitoneal, intramuscular, or intrathecal. The preferred method of administration can vary depending on various factors, e.g., the components of the pharmaceutical composition, the site of the 15 potential or actual bacterial infection, the bacterium involved, and the infection severity. The term "mammal" has its usual biological meaning referring to any organism of the Class Mammalia of higher vertebrates that nourish their young with milk secreted by mammary glands, e.g., mouse, rat, and, in particular, human, bovine, 20 sheep, swine, dog, and cat. In the context of treating a bacterial infection a "therapeutically effective amount" or pharmaceuticallyy effective amount" indicates an amount of an antibacterial agent, e.g., as disclosed for this invention, which has a therapeutic effect. This generally refers to the inhibition, to some extent, of the normal cellular 25 functioning of bacterial cells that renders or contributes to bacterial infection. The dose of antibacterial agent that is useful as a treatment is a "therapeutically effective amount." Thus, as used herein, a therapeutically effective amount means an amount of an antibacterial agent that produces the desired therapeutic effect as judged by clinical trial results and/or animal models. This amount 30 can be routinely determined by one skilled in the art and will vary depending on several factors, such as the particular bacterial strain involved and the particular antibacterial agent used. In connection with claims to methods of inhibiting bacteria and therapeutic or prophylactic treatments, "a compound active on a target of a bacteriophage inhibitor 35 protein" or terms of equivalent meaning differ from administration of or contact.wTth an intact phage naturally encoding the full-length inhibitor compound. While an intact phage may conceivably be incorporated in the present methods, the method at WO 00/32825 PCT/IB99/02040 26 least includes the use of an active compound as specified different from a full length inhibitor protein naturally encoded by a bacteriophage and/or a delivery or contacting method different from administration of or contact with an intact phage encoding the full-length protein. Similarly, pharmaceutical compositions described herein at least 5 include an active compound different from a full-length inhibitor protein naturally encoded by a bacteriophage or such a full-length protein is provided in the composition in a form different from being encoded by an intact phage. Preferably the methods and compositions do not include an intact phage. In accord with the above aspects, the invention also provides antibacterial 10 agents and compounds active on bacterial targets of bacteriophage inhibitor proteins or RNAs, where the target was uncharacterized as indicated above. As previously indicated, such active compounds include both novel compounds and compounds which had previously been identified for a purpose other than inhibition of bacteria. Such previously identified biologically active compounds can be used in 15 embodiments of the above methods of inhibiting and treating. In preferred embodiments, the targets, bacteriophage, and active compound are as described herein for methods of inhibiting and methods of treating. Preferably the agent or compound is formulated in a pharmaceutical composition which includes a pharmaceutically acceptable carrier, excipient, or diluent. In addition, the invention provides agents, 20 compounds, and pharmaceutical compositions where an active compound is active on an uncharacterized phage-specific site. In preferred embodiments, the target is as described for embodiments of aspects above. Likewise, the invention provides a method of making an antibacterial agent. 25 The method involves identifying a target of a bacteriophage inhibitor polypeptide or protein or RNA, screening a plurality of compounds to identify a compound active on the target, and synthesizing the compound in an amount sufficient to provide a therapeutic effect when administered to an organism infected by a bacterium naturally producing the target. In preferred embodiments, the identification of the target and 30 identification of active compounds include steps or methods and/or components as described above (or otherwise herein) for such identification. Likewise, the active compound can be as described above, including fragments and derivatives of phage inhibitor proteins, peptidomimetics, and small molecules. As recognized by those skilled in the art, peptides can be synthesized by expression systems and purified, or . 35 can be synthesized artificially. In preferred embodiments the inhibitory phage ORFT products is from S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus WO 00/32825 PCT/IB99/02040 27 pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014. As indicated above, sequence analysis of nucleotide and/or amino acid sequences can beneficially utilize computer analysis. Thus, in additional aspects the 5 invention provides computer-related hardware and media and methods utilizing and incorporating sequence data from uncharacterized phage, e.g., uncharacterized phage listed in Table 1, preferably at least one of Staphvlococcus aureus phage S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 029, 030, 038, or 041, or Enterococcus sp. phage 10 182 ORF 002, 008, or 014, or 44 AHJD, Enterococcus sp. phage 182, or Streptococcus pneumoniae phage Dp-1. In general, such aspects can facilitate the above-described aspects. Various embodiments involve the analysis of genetic sequence and encoded products, as applied to the evaluating bacteriophage inhibitor ORFs and compounds and fragments related thereto. The various sequence analyses, 15 as well as function analyses, can be used separately or in combination, as well as in preceding aspects and embodiments. Use in combination is often advantageous as the additional information allows more efficient prioritizing of phage ORFs for identification of those ORFs that provide bacteria-inhibiting function. In one aspect, the invention provides a computer-readable device which 20 includes at least one recorded amino acid or nucleotide sequence corresponding to one of the specified phage and a sequence analysis program for analyzing a nucleotide and/or amino acid sequence. The device is arranged such that the sequence information can be retrieved and analyzed using the analysis program. The analysis can identify, for example, homologous sequences or the indicated %s of the phage 25 genome and structural motifs. Preferably the sequence includes at least 1 phage ORF or encoded product, more preferably at least 10%, 20%, 30%, 40%, 50%, 70%, 90%, or 100% of the genomic phage ORFs and/or equivalent cDNA, RNA, or amino acid sequences. Preferably the sequence or sequences in the device are recorded in a medium such as a floppy disk, a computer hard drive, an optical disk, computer 30 random access memory (RAM), or magnetic tape. The program may also be recorded in such medium. The sequences can also include sequences from a plurality of different phage. In this context, the term "corresponding" indicates that the sequence is at least 95% identical, preferably at least 97% identical, and more preferably at least 99% 35 identical to a sequence from the specified phage genome, a ribonucleotide equivalent, a degenerate equivalent (utilizing one or more degenerate codons), or a homologous sequence, where the homolog provides functionally equivalent biological function.
WO 00/32825 PCT/IB99/02040 28 Similarly, the invention provides a computer analysis system for identifying biologically important portions of a bacteriophage genome. The system includes a data storage medium, e.g., as identified above, which has recorded thereon a nucleotide sequence corresponding to at least a portion of at least one uncharacterized 5 bacteriophage genome, a set of program instructions to allow searching of the sequence or sequences to analyze the sequence, and an output device where the portion includes at least the sequence length as specified in the preceding aspect. The output device is preferably a printer, a video display, or a recording medium. More one than one output device may be included. For each of the present computer-related 10 asepcts, the bacteriophage are preferably selected from the uncharacterized phage listed in Table 1, more preferably from bacteriophage 77, 3A, 96, 44 AHJD (S. aureus), Dp-1 (Streptococcus pneumoniae), or 182 (Enterococcus). In keeping with the computer device aspects, the invention also provides a method for identifying or characterizing a bacteriophage ORF by providing a 15 computer-based system for analyzing nucleotide or amino acid sequences, e.g., as describe above. The system includes a data storage medium which has recorded a sequences or sequences as described for the above devices, a set of instructions as in the preceding aspect, and an output device as in the preceding aspect. The method further involves analyzing at least one sequence, and outputting the analysis results to 20 at least one output device. In preferred embodiments, the analysis identifies a sequence similarity or homology with a sequence or sequences selected from bacterial ORFs encoding products with related biological function; ORFs encoding known inhibitors; and essential bacterial ORFs. Preferably the analysis identifies a probable biological 25 function based on identification of structural elements or characteristic or signature motifs of an encoded product or on sequence similarity or homology. Preferably the uncharacterized bacteriophage is from Table 1, more preferably at least one of bacteriophage 77, 3A, 96, 44 AHJD (S. aureus), Dp- 1 (Streptococcus pneumoniae), or 182 (Enterococcus). In preferred embodiments, the method also involves determining 30 at least a portion of the nucleotide sequence of at least one uncharacterized bacteriophage as indicated, and recording that sequence on data storage medium of the computer-based system. In preferred embodiments, the analysis identifies a sequence similarity of homology with a S. aureus phage 44AHJD ORF 1, 9, or 12, Streptococcus pneumoniae phage Dp-1 ORF 001, 002, 004, 008, 010, 013, 016, 021, 35 029, 030, 038, or 041, or Enterococcus sp. phage 182 ORF 002, 008, or 014.
WO 00/32825 PCT/IB99/02040 29 As used in the claims to describe the various inventive aspects and embodiments, "comprising" means including, but not limited to, whatever follows the word "comprising". Thus, use of the term "comprising" indicates that the listed elements are required or mandatory, but that other elements are optional and may or 5 may not be present. By "consisting of' is meant including, and limited to, whatever follows the phrase "consisting of'. Thus, the phrase "consisting of' indicates that the listed elements are required or mandatory, and that no other elements may be present. By "consisting essentially of' is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or 10 action specified in the disclosure for the listed elements. Thus, the phrase "consisting essentially of' indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements. Further embodiments will be apparent from the following Detailed Description 15 and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS 20 FIGURE IA and 1B are flow schematics showing the manipulations used to convert pTO02 1, an arsenite inducible vector containing the luciferase gene, into pTHA or pTM, two ars inducible vectors. Vector pTHA contains BamH I, Sal I, and Hind III cloning sites and a downstream HA epitope tag. Vector pTM contains Bam HI and Hind III cloning sites and no HA epitope tag. 25 FIGURE 2 is a schematic representation of the cloning steps involved to place the DNA segments of any of ORFs 17/ 19/ 43/ 102/104/182 or other sequences into pTHA to assess inhibitory potential. For subcloning into pTM or pT0021, Individual ORFs were amplified by the PCR using oligonucleotides targeting the ATG and stop 30 codons of the ORFs. Using this strategy, Bam HI and Hind III sites were positioned immediately upstream or downstream, respectively of the start and stop codons of each ORF. Following digestion with Bam HI and Hind III, the PCR fragments were subcloned into the same sites of pT0021 or pTM. Clones were verified by PCRand direct sequencing.
WO 00/32825 PCT/IB99/02040 30 FIGURE 3 shows a schematic representation of the functional assays used to characterize the bactericidal and bacteriostatic potential of all predicted ORFs (>33 amino acids) encoded by bacteriophage 77. Fig. 3A) Functional assay on semi-solid 5 support media. Fig. 3B) Functional assay in liquid culture. FIGURE 4A, B, and C is a bar graph showing the results of a screen in liquid media to assess bacteriostatic or bactericidal activity of 93 predicted ORFs (>33 amino acids) encoded by bacteriophage 77. Growth inhibition assays were performed 10 as detailed in the Detailed Description. The relative growth of Staphylococcus aureus transformants harboring a given bacteriophage 77 ORF (identified on the bottom of the graph), in the absence or presence of arsenite, is plotted relative to growth of a Staphylococcus aureus transformant containing ORF 5, a non-toxic bacteriophage 77 ORF (which is set at 100%). Each bar represents the average obtained from three 15 Staph A transformants grown in duplicate. Bacteriophage 77 ORFs showing significant growth inhibition consist of ORFs 17, 19, 102, 104, and 182. FIGURE 5 shows a block diagram of major components of a general purpose computer. 20 FIGURE 6 shows an ORF map for Streptococcus pneumoniae bacteriophage Dp-1 showing the ORF identifiers, genomic locations, and orientations of the 85 identified ORFs that were found to have ribosomal binding sites and thus are expected to be expressed. 25 FIGURE 7 shows a schematic representation of the arsenite-inducible expression system present in a shuttle vector designed to express individual Streptococcus bacteriophage Dp- 1 ORFs in Streptococcus. Various modifications can be readily made to such a vector, or other vectors can be readily constructed to 30 provide inducible expression of ORFs in a particular host bacterium using well-known techniques.
WO 00/32825 PCT/IB99/02040 31 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention may be more clearly understood from the following description. 5 The tables will first be briefly described. Table 1 is a listing of a large number of available bacteriophage that can be readily obtained and used in the present invention. Table 2 shows the complete nucleotide sequence of the genome of Staphylococcus aureus bacteriophage 77. 10 Table 3 shows a list of all the ORFs from Bacteriophage 77 that were screened in the functional assay to identify those with anti-microbial activity. Table 4 shows the predicted nucleotide sequence, predicted amino acid sequence, and physiochemical parameters of ORF 17/ 19/ 43/ 102/ 104/ 182]. These include the primary amino acid sequence of the predicted protein, the average 15 molecular weight, amino acid composition, theoretical pI, hydrophobicity map, and predicted secondary structure map. Table 5 shows homology search results. BLAST analysis was performed with ORFs 17/ 19/ 43/ 102/ 104/ 182 against NCBI non-redundant nucleotide and Swissprot databases. The results of this search indicate that: I) ORF 17 has no 20 significant homology to any gene in the NCBI non-NCBI non-redundant nucleotide database, II) ORF 19 has significant homology to one gene in the NCBI non redundant nucleotide database - the gene encoding ORF 59 of bacteriophage phi PVL, III) ORF 43 has significant homology to one gene in the NCBI non-redundant nucleotide database - the gene encoding ORF 39 of phi PVL, IV) ORF 102 has 25 significant homology to one gene in the NCBI non-redundant nucleotide database the gene encoding ORF 38 of phi PVL, V) ORF 104 has no significant homology to any gene in the NCBI non-redundant nucleotide database, VI) ORF 182 has significant homology to one gene in the NCBI non-redundant nucleotide database the gene encoding ORF 39 of phi PVL. 30 Table 6 is a table from Alberts et al., MOLECULAR BIOLOGY OF THE CELL 3 'd ed., showing the redundancy of the "universal" genetic code. Table 7 shows the complete nucleotide sequence of Staphylococcus aureus bacteriophage 3A.
WO 00/32825 PCT/IB99/02040 32 Table 8 is a listing of the ORFs identified in Staphylococcus aureus bacteriophage 3A. Table 9 shows the complete nucleotide sequence of Staphylococcus aureus bacteriophage 96. 5 Table 10 is a listing of the ORFs identified in Staphylococcus aureus bacteriophage 96. Table 11 is a listing of sequences deposited in the NCBI public database (GeneBank) for bacteriophage listed in Table 1. Table 12 is a listing of phage which encode a known lysis function, including 10 the identified lysis gene. Table 13 is a listing of bacteriophage which encode holin genes, where holin genes encode proteins which form pores and eventually enable other enzymes to kill the host bacterium. Table 14 is a listing of bacteriophage which encode kil genes. 15 Table 15 is a list of Staphylococcus aureus sequences identified by accession number which may include sequences from genes coding for target sequences for the phage 77-encoded antimicrobial proteins or peptides. The sequences were obtained by searching GenBank for listings. Table 16 shows the nucleotide sequence of the genome of Staphylococcus 20 aureus phage 44 AHJD. Table 17 lists and shows the sequence position of the 73 ORFs predicted to be encoded by Staphylococcus aureus bacteriophage 44 AHJD that are greater than 33 amino acids. Table 18 shows the ORF sequences and putative amino acid sequences for the 25 Staphylococcus aureus bacteriophage 44AHJD ORFs greater than 33 amino acids. Table 19 shows the similarities in sequence identified between predicted Staphylococcus aureus bacteriophage 44 AHJD ORFs and sequences present in public databases. Table 20 shows the homology alignments between predicted Staphylococcus 30 aureus bacteriophage 44AHJD ORFs and the corresponding protein sequences present in public sequence databases. Table 21 shows the complete nucleotide sequence of the genome of Enterococcus bacteriophage 182. Table 22 lists and shows the sequence position of the 80 ORFs identified in 35 bacteriophage 182 and that are greater than 33 amino acids.
WO 00/32825 PCT/IB99/02040 33 Table 23 shows the nucleotide and predicted amino acid sequence of all 80 ORFs identified in bacteriophage 182. Table 24 shows the similarities identified to date in sequence between Enterococcus phage 182 ORFs greater than 33 amino acids and sequences present in 5 public sequence databases. Table 25 shows the predicted amino acid sequence as well as the predicted secondary structures map for two Enterococcus bacteriophage 182 ORFs. Table 26 shows the homology alignments between predicted Enterococcus bacteriophage 182 ORFs and the corresponding protein sequences present in public 10 sequence databases. Table 27 list Enterococcus sequences listed in GenBank providing possible Enterococcal target sequences for inhibitory Enterococcus bacteriophage 182 ORFs and other compounds with antibacterial activity. Table 28 shows the complete nucleotide sequence of the genome of 15 Streptococcus bacteriophage Dp- 1. Table 29 lists and shows sequence position of the 273 ORFs identified in Pneumococcal bacteriophage Dp-1 that are greater than 33 amino acids, 85 of which are predicted to be expressed in Dp-1 as having a ribosomal binding site. That set of 85 ORFs is shown in the attached drawings. 20 Table 30 shows the nucleotide and predicted amino acid sequence of all 273 ORFs identified in bacteriophage Dp-1 that are identified as being expressed. Table 31 shows the similarities identified in sequence between Streptococcus phage Dp-1 ORFs greater than 33 amino acids and sequences present in public sequence databases. 25 Table 32 shows the 4731 bp sequence of Dp-l published by Sheehan et al., 1997). Table 33 lists Streptococcus pneumoniae sequences listed in GenBank providing possible target sequences for inhibitory Streptococcus pneumoniae bacteriophage Dp-1 ORFs and other compounds with antibacterial activity 30 Background: As indicated above, the present invention is concerned, in part, with the use of bacteriophage coding sequences and the encoded polypeptides or RNA transcripts to identify bacterial targets for potential new antibacterial agents. Thus, the invention 35 concerns the selection of relevant bacteria. Particularly relevant bacteria are those which are pathogens of a complex organism such as an animal, e.g., mammals, WO 00/32825 PCT/IB99/02040 34 reptiles, and birds, and plants. Examples include Stapylococcus aureus, Enterococcus species, and Streptococcus pneumoniae. However, the invention can be applied to any bacterium (whether pathogenic or not) for which bacteriophage are available or which are found to have cellular components closely homologous to components 5 targeted by phage of another bacterium. Thus, the invention also concerns the bacteriophage which can infect a selected bacterium. Identification of ORFs or products from the phage which inhibit the host bacterium both provides an inhibitor compound and allows identification of the bacterial target affected by the phage-encoded inhibitor. Such targets are thus 10 identified as potential targets for development of other antibacterial agents or inhibitors and the use of those targets to inhibit those bacteria. As indicated above, even if such a target is not initially identified in a particular bacterium, such a target can still be identified if a homologous target is identified in another bacterium. Usually, but not necessarily, such another bacterium would be a genetically closely 15 related bacterium. Indeed, in some cases, a phage-encoded inhibitor can also inhibit such a homologous bacterial cellular component. The demonstration that bacteriophage have adapted to inhibiting a host bacterium by acting on a particular cellular component or target provides a strong indication that that component is an appropriate target for developing and using 20 antibacterial agents, e.g., in therapeutic treatments. Thus, the present invention provides additional guidance over mere identification of bacterial essential genes, as the present invention also provides an indication of accessability of the target to an inhibitor, and an indication that the target is sufficiently stable over time (e.g., not subject to high rates of mutation) as phage acting on that target were able to develop 25 and persist. Thus, the present invention identifies a subset of essential cellular components which are particularly likely to be appropriate targets for development of antibacterial agents. The invention also, therefore, concerns the development or identification of inhibitors of bacteria, in addition to the phage-encoded inhibitory proteins (or RNA 30 transcripts), which are active on the targets of bacteriophage-encoded inhibitors. As described herein, such inhibitors can be of a variety of different types, but are preferably small molecules. The following description provides preferred methods for use in the various aspects of the invention. However, as those skilled in the art will readily recognize, 35 other approaches can be used to obtain and process relevant information. Thus-hi~ invention is not limited to the specifically described methods. In addition, the following description provides a set of steps in a particular order. That series of steps WO 00/32825 PCT/IB99/02040 35 describes the overall development involved in the present invention. However, it is clear that individual steps or portions of steps may be usefully practiced separately, and, further, that certain steps may be performed in a different order or even bypassed if appropriate information is already available or is provided by other sources or 5 methods. Selecting and Growing Phage, and Isolating DNA Conceptually, the first step involves selecting bacterial hosts of interest. Preferably, but not necessarily, such hosts will be pathogens of clinical importance. 10 Alternatively, because bacteria all share certain fundamental metabolic and structural features, these features can be targeted for study in one strain, for example a nonpathogenic one, and extrapolated to similarly succeed in pathogenic ones. Nonpathogenic strains may also exhibit initial advantages in being not only less dangerous, but also, for example, in having better growth and culturing characteristics 15 and/or better developed molecular biology techniques and reagents. Consequently, advantageously the invention provides the ability target virtually any bacteria, but preferably pathogenic bacteria, with antimicrobial compounds designed and/or developed using bacteriophage inhibitory proteins and peptides from phage with non pathogenic and/or pathogenic hosts. 20 We have selected Staphylococcus aureus, Streptococcus pneumoniae, various Enterococci, and Pseudomonas aeruginosa as initial exemplary pathogens. These bacteria are a major cause of morbidity and mortality in hospital-based infections, and the appearance of antibiotics resistance in all three organisms makes it increasingly difficult to treat benign infections involving these organisms. Such infections can 25 include, for example, otitis media, sinusitis, and skin, and airway infections (Neu, H.C. (1992). Science 257, 1064-1073). However, the approach described below is clearly applicable to any human bacterial pathogens including but not restricted to Mycobacterium tuberculosis, Nesseria gonorrhoeae, Haemophilus influenza, Acinobacter, Escherichia coli, Shigella dysenteria, Streptococcus pyogenes, 30 Helicobacterpylori, and Mycoplasma species. This invention can also be applied to the discovery of anti-bacterial compounds directed against pathogens of animals other than humans, for example, sheep, cattle, swine, dogs, cats, birds, and reptiles. Similarly, the invention is not limited to animals, but also applies to plants and plant pathogens. 35 In general, the bacteria are grown according to standard methodologies employed in the art, including solid, semi-solid or liquid culturing, which procedures can be found in or extrapolated from standard sources such as Maloy, S.R., Stewart, WO 00/32825 PCT/IB99/02040 36 V.J., and Taylor, R.K. Genetic Analysis of Pathogenic Bacteria (1996) Cold Spring Harbor Laboratory Press, or Maniatis, T. et al. (1989} Molecular Cloning: A Laboratory Manual, Cold Spring Harbor University Press, Cold Spring, N.Y.; or Ausubel, F.M. et al. (1994) Current Protocols in Molecular Biologv. John Wiley & 5 Sons, Secaucus, N.J. Culture conditions are selected which are adapted to the particular bacterium generally using culture conditions known in the art as appropriate, or adaptations of those conditions. Nucleic acids within these bacteria can be routinely extracted through common procedures such as described in the above-referenced manuals and as generally known 10 to those skilled in the art. Those nucleic acid stocks can then be used to practice the other inventive aspects described below. Selection and Growth of Bacteriophage, and Isolation of DNA The second step involves assembling a group of bacteriophages (phage 15 collection) for one or more of the targeted bacterial hosts. While the invention can be utilized with a single bacteriophage for a pathogen or other bacterium, it is preferable to utilize a plurality of phage for each bacterium, as comparisons between a plurality of such phage provides useful additional information. Non-limiting examples of phage and sources for some of the above-mentioned pathogenic bacteria are found in 20 Table 1. The criteria used to select such phages is that they are infectious for the microbe targeted, and replicate in, lyse, or otherwise inhibit growth of the bacterium in a measurable fashion. These phages can be very different from one another (representing different families), as judged by criteria such as morphology (head, tail, plate, etc.), and similarity of genome nucleotide sequence (cross-hybridization). Since 25 such diverse bacteriophages are expected to block bacterial host metabolism and ultimately inhibit by a variety of mechanisms, their combined study will lead to the identification of different mechanisms by which the phages independently inhibit bacterial targets. Examples include degradation of host DNA (Parson K.A., and Snustad, D.P. (1975). J Virol. 15, 221-444) and inhibition of host RNA transcription 30 (Severinova, E., Severinov, K. and Darst, S.A. (1998). J.Mol. Biol. 279, 9-18). This, in turn, yields novel information on phage proteins that can inhibit the targeted microbe. As explained below, this 1) forms the basis of novel drug discovery efforts based on knowledge of the primary amino acid sequence of the phage inhibitor protein (e.g., peptide fragments or peptidomimetics) and/or 2) leads to the 35 identification of bacterial biochemical pathways, the proteins of which are essentiiaor significant for survival of the targeted microbe, and which enzymatic steps or WO 00/32825 PCT/IB99/02040 37 chemical reactions can be targeted by classical drug discovery methods using molecular inhibitors, for example, small molecule inhibitors. Bacteriophage are generally either of two types, lytic or filamentous, meaning they either outright destroy their host and seek out new hosts after replication, or else 5 continuously propogate and extrude progeny phage from the same host without destroying it. Regardless of the phage life cycle and type, preferred embodiments incorporate phage which impede cell growth in measurable fashion and preferably stop cell growth. To this end, lytic phage are preferred, although certain nonlytic species may also suffice, e.g., if sufficiently bacteriostatic. 10 Various procedures that are commonly understood by those of skill in the art can be routinely employed to grow, isolate, and purify phage. Such procedures are exemplified by those found in such common laboratory aids such as Maloy, S.R., Stewart, V.J., and Taylor, R.K. Genetic Analysis of Pathogenic Bacteria (1996) Cold Spring Harbor Laboratory Press; Maniatis, T. et al. (1989) Molecular Cloning: A 15 Laboratory Manual, Cold Spring Harbor University Press, Cold Spring, N.Y.; and Ausubel, F.M. et al. (eds.) (1994) Current Protocols in Molecular Biology. John Wiley & Sons, Secaucus, N.J. The techniques generally involve the culturing of infected bacterial cells that are lysed naturally and/or chemically assisted, for example, by the use of an organic solvent such as chloroform that destroys the host 20 cells thereby liberating the phage within. Following this, the cellular debris is centrifuged away from the supernatant containing the phage particles, and the phage then subsequently and selectively precipitated out of the supernatant using various methods usually employing the use of alcohols and/or other chemical compounds such as polyethylene glycol (PEG). The resulting phage can be further purified using 25 various density gradient/centrifugation methodologies. The resulting phage are then chemically lysed, thereby releasing their nucleic acids that can be conveniently precipitated out of the supernatant to yield a viral nucleic acid supply of the phage of interest. Exemplary bacteriophage are indicated in Table 1, along with sources where 30 those phage may be obtained. Exemplary bacteria include the reference bacteria for the identified bacteriophage, available from the same sources. Characterizing Bacteriophage Genomes for ORFs 35 The third step involves systematically characterizing the genetic information contained in the phage genome. Within this genetic information is the sequence of all RNAs and proteins encoded by the phage, including those that are essential or WO 00/32825 PCT/IB99/02040 38 instrumental in inhibiting their host. This characterization is preferably done in a systematic fashion. For example, this can be done by first isolating high molecular weight genomic DNA from the phage using standard bacterial lysis methods, followed by phage purification using density gradient ultracentrifugation, and extraction of 5 nucleic acid from the purified phage preparation. The high molecular weight DNA is then analyzed to determine its size and to evaluate a proper strategy for its sequencing. The DNA is broken down into smaller size fragments by sonication or partial digestion with frequently cutting restriction enzymes such as Sau3A to yield predominantly 1 to 2 kilobase length DNA, which DNA can then be resolved by gel 10 electrophoresis followed by extraction from the gel. The ends of the fragments are enzymatically treated to render them suitable for cloning and the pools of fragments are cloned in a bacterial plasmid to generate a library of the phage genome. Several hundred of these random DNA fragments contained in the plasmid vector are isolated as clones after introduction into an 15 appropriate bacterium, usually Escherichia coli. They are then individually expanded in culture and the DNA from each individual clone is purified. The nucleotide sequences of the inserts of these clones are determined by standard automated or manual methods, using oligonucleotide primers located on either side of the cloning site to direct polymerase mediated sequencing (e.g., the Sanger sequencing method or 20 a modification of that method). Other sequencing methods can also be used. The sequence of individual clones is then deposited in a computer, and specific software programs (for example, SequencherTM, Gene Codes Corp.) are used to look for overlap between the various sequences, resulting in ordering of contig sequences and ultimately providing the complete sequence of the entire bacteriophage 25 genome (one such example is given in Table 2 for Staphylococcus aureus bacteriophage 77; others are also provided herein). This complete nucleotide sequence is preferably determined with a redundancy of at least 3- to 5-fold (number of independent sequencing events covering the same region) in order to minimize sequencing errors. 30 Preferably, the bacterial strain used as a phage host should not possess any other innate plasmids, transposons, or other phage or incompatible sequences that would complicate or otherwise make the various manipulations and analyses more difficult. Commercially available computer software programs are used to translate the 35 nucleotide sequence of the phage to identify all protein sequences encoded by the phage (hereafter called open reading frames or ORFs). (Customized software can clearly also be used.) As phages are known to transcribe their genome into RNA from WO 00/32825 PCT/IB99/02040 39 both strands, in both directions, and sometimes in more than one frame for the same sequence, this exercise is done for both strands and in all six possible reading frames. As evolutionary constraints have forced the phage to conserve all of its vital protein sequences in as small a genome as possible, it is straightforward to identify all the 5 proteins encoded by the phage by simple examination of the 6 translation frames of the genome. Once these ORFs are identified, they are cataloged into a phage proteome database (Table 3 lists ORFs identified from phage 77; ORF lists are also provided for other exemplary phage). This analysis is preferably performed for each phage under study. The process of ORF identification can be varied depending on the 10 desired results. For example, the minimum length for the putative encoded polypeptide can be varied, and/or putative coding regions that have an associated Shine-Dalgarno sequence can be selected. In the case of phage 77 ORFs, such parameter adjustment was performed and resulted in the identification of ORFs as listed herein. Different parameters had resulted in the identification of the ORFs 15 listed in the preceding U.S. Provisional Application 60/110,992, filed December 3, 1998, which is hereby incorporated by reference in its entirety. Exemplary phage 77 ORFs identified in that provisional application and as identified herein are shown in the following table: ORF ID Genomic a.a. Start ORF ID Genomic a.a. Start from position size codon from position size codon 60/110,992 241/190 770RF016 2369-24024 251 |fTTG 770RF017 23269-23982 237 ATG 770RF019 39845-40501 218 ATA 770RF019 39851-40501 216 ATG 770RF050 29268-29564 98 ATG 770RF182 29268-29564 98 ATG 770RF050 29268-29564 98 ATG 770RF043 29304-29564 86 ATG 770RF067 34312-34551 79 CTG 770RF104 34393-34551 52 ATG 770RF146 29051-29212 53 ATG 770RF102 29051-29212 53 ATG 20 Identifying and Characterizing Inhibitory Phage ORFs The fourth step entails identifying the phage protein or proteins or RNA transcripts that have the ability to inhibit their bacterial hosts. This can be 25 accomplished, for example, by either or both of two non-mutually exclusive methods. The first method makes use of bioinformatics. Over the past few years, a large amount of nucleotide sequence information and corresponding translated products have become available through large genome sequencing projects for a variety of organisms including mammals, insects, plants, unicellular eukaryotes (yeast and 30 fungi), as well as several bacterial genomes such as E. coli, Mycobacterium tuberculosis, Bacillus subtilis, Staphylococcus aureus and many others. Such sequences have been deposited in public databases (for example, non-redundant WO 00/32825 PCT/IB99/02040 40 sequence database at GenBank and SwissProt protein sequence database) (http://www.ncbi.nlm.nih.gov)) and can be freely accessed to compare any specific query sequence to those present in such databases. For example, GenBank contains over 1.6 billion nucleotides corresponding to 2.3 million sequence records. Several 5 computer programs and servers (e.g., TBLASTN) have been created to allow the rapid identification of homology between any given sequence from one organism to that of another present in such databases, and such programs are public and available free of charge. In addition, it has been well established that basic biochemical pathways can 10 be conserved in very distant organisms (for example bacteria and man), and that the proteins performing the various enzymatic steps in these pathways are themselves conserved at the amino acid sequence level. Thus, proteins performing similar functions (e.g. DNA repair, RNA transcription, RNA translation) have frequently preserved key structural signatures, identifiable by similarities across regions of 15 proteins (domains and motifs). The antimicrobials of the present invention will preferably target features and targets that are highly characteristic or conserved in microbes, and not higher organisms. Most genomes encode individual proteins or groups of proteins that can be assembled into protein families that have been evolutionarily conserved. Therefore, 20 similarity between a new query sequence and that of a member of a protein family (reference sequences from public databases) can immediately suggest a biochemical function for the novel query sequence, which in our case is a phage ORF. The sequence homology between individual members of evolutionarily distant members of a protein family is usually not randomly distributed along the entire 25 length of the sequence but is often clustered into "motifs" and "domains". These correspond to key three-dimensional folds that form key catalytic and/or regulatory structures that perform key biochemical function(s) for the group of proteins. Commercially available computer software programs can identify such motifs in a new query sequence, again providing functional information for the query sequence. 30 Such structural and functional motifs have also been derived from the combined analysis of primary sequence databases (protein sequences) and protein structure databases (X-ray crystallography, nuclear magnetic resonance) using so-called "threading" methods (Rost B,1 and Sander C. (1 996).Ann. Rev. Biophy. BiomoL. Struct. 25, 113-136). 35 Such motifs and folds are themselves deposited in public databases which-can be directly accessed (for example, SwissProt database; 3D-ALI at EMBL, Heidelberg; PROSITE). This basic exercise leads to a structural homology map in which each of WO 00/32825 PCT/IB99/02040 41 the phage ORFs has been probed for such similarities, and where initial structural and functional hits are identified (selected examples of sequence homologies detected between individual ORFs from the genome of Staphylococcus aureus bacteriophage 77 and sequences deposited in public databases are shown in Table 5 for ORFs 5 17/19/43/102/104/182). This analysis can point out phage proteins with similarity to proteins from other phages (such as those for E. coli) playing an important role in the basic biochemical pathways of the phage (such as DNA replication, RNA transcription, tRNAs, coat protein and assembly). Selected examples of such proteins include 10 integrase and capsid protein. Therefore, this analysis enables identification and elimination of non-essential ORFs as candidates for an inhibitor function, as well as the identification of (potentially) useful ones. In addition, this analysis can point out specific ORFs as possible inhibitor ORFs. For example these ORFs may encode proteins or enzymes that alter bacterial 15 cell structure, metabolism or physiology, and ultimately viability. Examples of such proteins present in the genome of Staphylococcus aureus bacteriophage 77 include orfl4 (deoxyuridine triphosphatase from bacteriophage T5), and orfl5 (sialidase). (These ORF identifications are as listed in provisional application 60/110,992.) Other examples include ORFs 9 and 12 of S. aureus phage 44 AHJD, which encode the 20 putative lysis functions found in many bacteriophages - a "holin" and an "amidase". In addition, it is well known that bacterial and eukaryotic viruses can usurp pathways from their host in order to use them to their advantage in blocking host cellular pathways upon infection. The phage can achieve this by 1) directly producing an inhibitor of a key host pathway (e.g. T7 gene 0.5 and 2), 2) directly producing a 25 novel activity (e.g. T4 DNA polymerase), and 3) altering concentrations of cell components by producing similar functions (e.g. T4 transfer RNAs). The identification of sequence similarity between phage ORFs and bacterial host genome sequences will be highly indicative of such a mechanism. (Selected examples of such homologies are listed in Figure 4 of the provisional application 60/110,992 and 30 include orf4 (homologous to autolysin), orf20 (hypothetical protein from Staphyloccus aureus) and orf29 (hypothetical protein from Staphyloccus aureus.)) These ORFs can be analyzed by a standard biochemical approach to directly test their inhibitor functions (e.g., as described below). Alternatively, a homology search may reveal that a given phage ORF is related 35 to a protein present in the databases having an activity known to be inhibitory, (e.P inhibitor of host RNA polymerase by E. coli bacteriophage T7. Such a finding would implicate the phage ORF product in a related activity. This will also suggest that a WO 00/32825 PCT/IB99/02040 42 new antimicrobial could be derived by a mimetic approach (e.g., peptidomimetic) imitating this function or by a small molecule inhibitor to the bacterial target of the phage ORF, or any steps in the relevant host metabolic pathway, e.g., high throughput screening of small molecule libraries. Selected examples of such similarity between 5 ORFs of Staphyloccus aureus bacteriophage 77 and proteins with inhibitor functions for bacterial hosts are listed in Figure 4 of the provisional application 60/110,992. These include orf9 (similar to bacteriophage P1 kilA function), and orf4 (autolysin of Staphylococcus aureus, amidase enzymatic activity). A reason for the biochemical study of individual ORFs for inhibitor function is 10 that their expression or overexpression will block cellular pathways of the host, ultimately leading to arrest and/or inhibition of host metabolism. In addition, such ORFs can alter host metabolism in different ways, including modification of pathogenicity. Therefore, individual ORFs identified above are expressed, preferably overexpressed, in the host and the effect of this expression or overexpression on host 15 metabolism and viability is measured. This approach can be systematically applied to every ORF of the phage, if necessary, and does not rely on the absolute identification of candidate ORFs by bioinformatics. Individual ORFs are resynthesized from the phage genomic DNA, e.g., by the polymerase chain reaction (PCR), preferably using oligonucleotide primers flanking the ORF on either side. These single ORFs are 20 preferably engineered so that they contain appropriate cloning sites at their extremities to allow their introduction into a new bacterial expression plasmid, allowing propagation in a standard bacterial host such as E. coli, but containing the necessary information for plasmid replication in the target microbe such as S. aureus (hereafter referred to as shuttle vector). Shuttle vectors and their use are well known in the art. 25 Such shuttle vectors preferably also contain regulatory sequences that allow inducible expression of the introduced ORF. As the candidate ORF may encode an inhibitor function that will eliminate the host, it is beneficial that it not be expressed prior to testing for activity. Thus, screening for such sequences when expressed in a constitutive fashion is less likely to be successful when the inhibitor is lethal. In the 30 exemplary inducible system presented in Figure 1A, 1B, 2, and 7, regulatory sequences from the ars operon of S. aureus are used to direct individual ORF expression in S. aureus (or other bacteria in which the ars system is functional). The ars operon encodes a series of proteins which normally mediate the extrusion of arsenite and other trivalent oxyanions from the cells when they are exposed to such 35 toxic substances in their environment. The operon encoding this detoxifying mechanism is normally silent and only induced when arsenite-related compounds are WO 00/32825 PCT/IB99/02040 43 present. (Tauriainen, S. et al. (1997) App. Env. Microb., Vol. 63, No. 11, p. 4456 4461.) Therefore, individual phage ORFs can be expressed in S. aureus in an inducible fashion by adding to the culture medium non-toxic arsenite concentrations 5 during the growth of individual S. aureus clones expressing such individual phage ORFs. Toxicity of the phage inhibitor ORF for the host is monitored by reduction or arrest of growth under induction conditions, as measured by optical density in liquid culture or after plating the induced cultures on solid medium. Subsequently, interference of the phage ORF with the host biochemical pathways ultimately leading 10 to reduced or arrested host metabolism can be measured by pulse-chase experiments using radiolabeled precursors of either DNA replication, RNA transcription, or protein synthesis. Similar constructs can be made and used for other bacteria using well known techniques. Those skilled in the art are familiar with a variety of other inducible systems 15 which can also be used for the controlled expression of phage ORFs, including, for example, lactose (see e.g., Stratagene's LacSwitchTMII system; La Jolla, CA) and tetracycline-based systems (see, e.g. Clontech's Tet On/Tet OffTM system; Palo Alto, CA). The arsenite-inducible system described is further depicted in Figures 1, 2 and 7. The selection or construction of shuttle vectors and the selection and use of 20 inducible systems are well known and thus other shuttle vectors appropriate for other bacteria can be readily provided by those skilled in the art, e.g., for use in other bacterial species. Standard methodologies for expressing proteins from constructs, and isolating and manipulating those proteins, for example in cross-linking and affinity 25 chromatography studies, may be found in various commonly available and known laboratory manuals. See, e.g., Current Protocols in Protein Science, John Wiley & Sons, Secaucus, N.J., and Maniatis, T. et al. (1989} Molecular Cloning: A Laboratory Manual, Cold Spring Harbor University Press, Cold Spring, N.Y. It has been found that certain phage or other viruses inhibit host cells, at least 30 in part, by producing an antisense RNA which binds to and inhibits translation from a bacterial RNA seqeunce. Thus, in the case of potentially inhibitor RNA transcripts encoded by the phage genome, a strong indicator of a possible inhibitory function is provided by the identification of phage sequence which is the identical to or fully complementary (or with only a small percentage of mismatch, e.g., <10%, preferably 35 less than 5%, most preferably less than 3%, to a bacterial sequence. This approachIfs convenient in the case of bacteria that have been essentially completely sequenced, as the comparison can be performed by computer using public database information.
WO 00/32825 PCT/IB99/02040 44 The inhibitory effect of the transcript can be confirmed using expression of the phage sequence in a host bacterium. If needed, such inhibitory can also be tested by transfecting the cells with a vector that will transcribe the phage sequence to form RNA in such manner that the RNA produced will not be translated into a polypeptide. 5 Inhibition under such conditions provides a strong indication that the inhibition is due to the transcript rather than to an encoded polypeptide. In an alternative, the expression of an ORF in a host bacterium is found to be inhibitory, but the inhibition is found to be due to an RNA product of the genomic coding region. For antisense inhibition, the sequence of the bacterial target nucleic 10 acid sequence can be identified by inspection of the phage sequence, and the full sequence of the relevant coding region for the bacterial product can be found from a database of the bacterial genomic sequence or can be isolated by standard techniques (e.g., a clone in a genomic library can be isolated which contains the full bacterial ORF, and then sequenced). 15 In either case, the identification of a target which is inhibited by an RNA transcript produced by a phage provides both the possible inhibition of bacteria naturally containing the same target nucleic acid sequence, as well as the ability to use the target sequence in screening for other types of compounds which will act directly on the target nucleic acid sequence or on a polypeptide product expressed or 20 regulated, at least in part, by the target of the inhibitory phage RNA. In some cases it will be found that the target of an inhibitory phage RNA or protein has previously been found to be a target of an inhibitory phage RNA or protein has previously been found to be a target for an antibacterial agent. In such cases, the phage inhibitor can still provide useful information if it is found that the 25 phage-encoded product acts at a different site than the previously identified antibacterial agent or inhibitor, i.e., acts at a phage-specific site. For many targets, action at a different site provides highly beneficial characteristics and/or information. For example, an alternate site of inhibitor action can at least partially overcome a resistance mechanism in a bacterium. As an illustration, in many cases, resistance is 30 due, in large part, to altered binding characteristics of the immediate target to the antibacterial agent. The altered binding is due to a structural change which prevents or destabilizes the binding. However, the structural change is frequently quite local, so that compounds which bind at different local sites will b unaffected or affected to a much lesser degree. Indeed, in some cases the local sites will be on a different 35 molecule and so may be completely unaffected by the local structural change czealing resistance to the original agent(s). An example of resistance due to altered binding is WO 00/32825 PCT/IB99/02040 45 provided by methicillin-resistant Staphylococcus aureus, in which the resistance is due to an altered penicillin-binding protein. In other cases, a new site of action can have improved accessibility as compared to a site acted on by a previously identified agent. This can, for example, 5 assist in allowing effective treatment at lower doses, or in allowing access by a larger range of types of compounds, potentially allowing identification of more potential active agents. Another advantage is that the structural characteristics of a different site of action will lead to identification and/or development of inhibitors with different 10 structures and different pharmacological parameter. This can allow a greater range of possibilities when selecting an antibacterial agent. Yet further, different sites often produce different inhibitory characteristics in the target organism. This is commonly the case for multi-domain target proteins. Thus, inhibition targeting an alternate site can produce more efficacious action, e.g., 15 faster killing, slower development of resistance, lower numbers of surviving cells, and different secondary effects (for example, different nutrient utilization). Stavhvlococcus aureus phase 77 As indicated above, the present invention is concerned, in part, with the use of 20 bacteriophage 77 coding sequences and the encoded polypeptides or RNA transcripts to identify bacterial targets for potential new antibacterial agents. As described, phage 77 ORFs 17, 19, 43, 102, 104, and 182 have been found to have bacteria inhibiting function. Identification of ORFs 17, 19, 43, 102, 104, and 182 and products from the phage which inhibit the host bacterium both provides an 25 inhibitor compound and allows identification of the bacterial target affected by the phage-encoded inhibitor. Such a target is thus identified as a potential target for development of other antibacterial agents or inhibitors and the use of those targets to inhibit those bacteria. As indicated above, even if such a target is not initially identified in a particular bacterium, such a target can still be identified if a 30 homologous target is identified in another bacterium. Usually, but not necessarily, such another bacterium would be a genetically closely related bacterium. Indeed, in some cases, an inhibitor encoded by phage 77 ORF 17, 19, 43, 102, 104, or 182 can also inhibit such a homologous bacterial cellular component. Possible bacterial target sequences are described herein by reference to sequence 35 source sites. In preferred embodiments, the sequence encoding the target corresponds WO 00/32825 PCT/IB99/02040 46 to a S. aureus nucleic acid sequence available from numerous sources including S. aureus sequences deposited in GenBank, S. aureus sequences found in European Patent Application No. 97100110.7 to Human Genome Sciences, Inc. filed January 7, 1997, S. aureus sequences available from TIGR at 5 http://www.tiur.org/tdb/mdb/mdb.html, and S. aureus sequences available from the Oklahoma University S. aureus sequencing project at the following URL: http://www.zenome.ou.edu/staph new.html. Such possible targets are particularly applicable to S aureus phages 77, 3A, 96, and 44 AHJD. The amino acid sequence of a polypeptide target is readily provided by 10 translating the corresponding coding region. For the sake of brevity, the sequences are not reproduced herein. Also, in preferred embodiments, a target sequence corresponds to a S. aureus coding sequence corresponding to a sequence listed in Table 15 herein. The listing in Table 15 describes S. aureus sequences currently listed with GenBank. Again, for the sake of brevity, the sequences are described by 15 reference to the database accession numbers instead of being written out in full herein. In cases where an entry for a coding region is not complete, the complete sequence can be readily obtained by routine methods, e.g., by isolating a clone in a phage host S. aureus genomic library, and sequencing the clone insert to provide the relevant coding region. The boundaries of the coding region can be identified by conventional 20 sequence analysis and/or by expression in a bacterium in which the endogenous copy of the coding region has been inactivated and using subcloning to identify the functional start and stop codons for the coding region. Staphvloccus aureus phage 44 AHJD 25 The present invention also can utilize the identification of naturally occuring DNA sequence elements within Staphylococcus aureus bacteriophage 44AHJD which encode proteins with antimicrobial activity. Such identification can utilize bioinformatics identification of specific proteins (ORFs) utilized by Staphylococcus aureus bacteriophage 44AHJD during the viral life 30 cycle, resulting in a slowing or arrest of growth of the bacterial host, or in death, of the Staphylococcus aureus host including lysis of the infected bacteria. Thus, some of the bacteriophage 44AHJD DNA sequences encoding these proteins (ORFs) are predicted to encode antimicrobial functions. Information derived from these DNA sequences and translated ORFs can, in turn, be utilized to develop inhibitory 35 compounds by peptidomimetics that can also function as antimicrobials. In addition, the identification of the host bacterial proteins that are targeted and inhibited by the WO 00/32825 PCT/IB99/02040 47 antimicrobial bacteriophage ORFs can themselves provide novel targets for drug discovery. The methodology described above is used to identify and characterize DNA sequences from Staphylococcus sp. bacteriophage 44 AHJD that have antimicrobial 5 activity. As described in the Examples, the Staphylococcus aureus propagating strain (PS 44A), obtained from the Felix d'Herelle Reference Centre (#HER 1101), was used as a host to propagate its phage 44AHJD, also obtained from the Felix d'Herelle Reference Centre (#HER 101). By sequencing, we found that bacteriophage 44AHJD consists of 16,668 bp (Table 16) predicted to encode 73 ORFs greater than 33 amino 10 acids (Tables 17 & 18). Computational analysis of the predicted protein products of Staphylococcus aureus bacteriophage 44AHJD identified homolgs in public sequence databases as listed inTable 19 and 20, along with the accompanying list of related proteins. From this analysis, it is apparent that 3 genes (ORF 3, 7, and 8) are related to 15 structural proteins found in other bacteriophages. These include genes predicted to encode a tail protein (ORF 3), an upper collar/connector protein of the phage virion (ORF 7), and a lower collar protein (ORF 8). Bioinformatics has also identified one gene whose product is likely involved in phage DNA synthesis. One gene (ORF 1) shows significant homology to DNA polymerases of a number of bacteriophages, 20 bacteria and fungi, and the product of this gene is likely responsible for replicating the genetic material of bacteriophage 44AHJD. ORF 2 encodes a protein with homology to the dinC gene of Bacillus subtilis that encodes a protein involved in teichoic acid biosynthesis. Teichoic acid is a polyphosphate polymer found in some, but not all, Gram positive organisms (and not in Gram negative organisms), where it 25 is attached to the peptidoglycan layer. The phage protein may thus be involved in the synthesis of this material for incorporation into the cell wall, allowing enhanced lysis by the phage lysis enzymes or, as many enzymes can function in "reverse reactions", may be involved in its degradation allowing for penetration of the peptidoglycan and phage genome entry into the cell following adsorption. The similarity between 30 Staphylococcus aureus bacteriophage 44AHJD and E. coli phage T7 indicates that they may share similar mechanisms of replication and growth. Both phages belonito the Pododviridae Family of bacteriophages and are members of the "T7-like" Genus of this Family (Ackermann and DuBow; VIth ICTV Report).
WO 00/32825 PCT/IB99/02040 48 Two genes, ORF 9 and 12, were identified with the potential to encode antimicrobial protein products. The homology alignments are shown in Tables 19 and 20. The predicted product of ORF 9 is related to a class of genes which encodes lysozyme-like functions, enzymes which cleave linkages in the mucopolysaccharide 5 cell wall structure of a variety of micro-organisms, including that from the Staphylococcus aureus bacteriophage Twort. ORF 12 of Staphylococcus aureus bacteriophage 44AHJD shows homology to a set of lysis proteins from several bacteriophages. These lysis proteins are also referred to as holins, and represent phage-encoded lysis functions required for transit of the phage murein hydrolases 10 (lysozyme) to the periplasm, where it can digest the cell wall and thus lyse the bacterium. Thus, in particular embodiments, the present invention provides a nucleic acid sequence isolated from Staphylococcus aureus bacteriophage 44AHJD comprising at least a portion of one of the genes described above with antimicrobial activity. For 15 example, ORF 1 encodes a DNA polymerase function. This polymerase may utilize host-derived accessory proteins for its activity when replicating the phage template, sequestering such proteins from use by the bacterial polymerase, resulting in inhibition of DNA replication, cell division, and cell growth. Alternatively, ORF 9 directly encodes a polypeptide with antimicrobial activity. ORF 9 is predicted to 20 encode an amidase, a protein known to act as a cell wall degrading enzyme. ORF 12 likely encodes a holin function required for transit of the phage amidase (gene 9 product) to the periplasm. When this type of gene product from Bacillus phage phi 29 (gene 14), was cloned in Escherichia coli, cell death ensued (Steiner et al., 1993). Thus, production of proteins from Bacillus phage phi 29 gene 14 in E. coli resulted in 25 cell death, whereas production of protein from Bacillus phage phi 29 gene 14 concomitantly with the phi 29 lysozyme or unrelated murein-degrading enzymes led to lysis, suggesting that membrane-bound protein 14 induces a nonspecific lesion in the cytoplasmic membrane (Steiner et al., 1993). The present invention also provides the use of the Staphylococcus 30 bacteriophage 44 AHJD antimicrobial ORFs or ORF products as pharmacological agents, either wholly or in part and derivatives, as well as the use of correspondilig peptidomimetics, developed from amino acid or nucleotide sequence knowledge derived from Staphylococcus bacteriophage 44 AHJD killer ORFs.
WO 00/32825 PCT/IB99/02040 49 Enterococcus phage 182 Bacteriophage 182 was obtained from the Felix D'Herelle phage collection (Ste. Foy, Quebec) and infects Enterococcus sp. Group D. The genome of 5 Enterococcus bacteriophage 182 consists of 17,833 bp (Table 21) and is predicted to encode 80 ORFs greater than 33 amino acids (Tables 22 and 23). Computational analysis of the predicted protein products of Enterococcus bacteriophage 182 was performed in order to identify protein products related to those deposited in public databases. Bacteriophage 182 protein products which detected sequences with 10 significant sequence similarity in public databases are listed in Table 24 and 26, along with the accompanying list of related proteins. From this analysis, it is apparent that 5 genes (ORF 001, 004, 007, 009, and 011) are related to structural proteins of several Bacillus phages - Bacillus bacteriophage PZA, phi-29, and B103. These include genes predicted to encode a tail 15 protein (ORF 001), a head protein (ORF 004), and upper collar protein (ORF 007), a lower collar protein (ORF 009), and a pre-neck appendage protein (ORF 011). Two gene products are predicted to encode genes which direct phage morphogenesis these are ORF 005 and 019. Bioinformatics has also identified three genes whose products are likely 20 involved in phage DNA synthesis. One gene, ORF 002 shows significant homology to DNA polymerases of a number of bacteriophages, and the product of this gene is likely responsible for replicating the genetic material of bacteriophage 182. ORF 006 encodes a protein with homology to the encapsidation proteins of several other bacteriophages, including Bacillus phage phi-29 (P11014), PZA (P07541), and B103 25 (X99260) and Streptococcus phage CP-1 (Z47794). These gene products catalyze the in vivo and in vitro genome-encapsidation reaction (Garvey et al., 1985). Proteins involved in genome packaging have been shown to have additional activities that affect biochemical reactions in other phages and their hosts. For example, the coat protein of the RNA bacteriophage MS2 interacts with viral RNA to translationally 30 repress replicase synthesis (Pickett and Peabody, 1993). This protein-RNA interaction also plays a role in genome encapsidation, enveloping a single copy of the viral genome in a protein shell composed of many molecules of coat protein. In addition, the bacteriophage k terminase enzyme can be lethal to E. coli when expressed, WO 00/32825 PCT/IB99/02040 50 suggesting cleavage of packaging sites in the bacterial chromosome. Also present within bacteriophage 182 is a gene, ORF 010, that encodes a protein that is related to the terminal proteins of Bacillus phage Nf (P06812), Bacillus phage GA-i (X96987) and Bacillus phage B103 (X99260). DNA terminal proteins are linked to the 5' ends 5 of both strands of the genome and are essential for DNA replication playing a role in initial priming of DNA replication. The similarity between Enterococcus bacteriophage 182 and Bacillus phages phi-29, PZA, and B103 indicates that they may share similar mechanisms of replication and growth. Protein-primed DNA replication is a well described phenomenon, and in the phi-29-like phages, the ends of 10 the DNA serve as origins and termini of replication (Guti6rrez et al., 1986; Yoshikawa et al., 1985). There is also a gene (ORF 015) that encodes a protein showing homology to an early protein product of Bacillus bacteriophage PZA and the single-strand nucleic acid binding protein of bacteriophage B 103. 15 Two genes, ORF 008 and 014, were identified with the potential to encode anti-microbial protein products. The homology alignments are shown in Tables 24 & 26 and biochemical features of the predicted polypeptides shown in Table 25. The predicted product of ORF 008 is related to a class of genes which encodes lysozyme like functions, enzymes which cleave linkages in the mucopolysaccharide cell wall 20 structure of a variety of micro-organisms. ORF 014 of Enterococcus 182 shows homology to a set of lysis proteins from Bacillus bacteriophage phi-29, PZA, and B103. These lysis proteins are also referred to as holins and represent phage encoded lysis functions required for transit of the phage murein hydrolases (lysozyme) to the periplasm, where it can digest the outer cell wall and thus lyse the bacterium. 25 Thus, the present invention provides a nucleic acid sequence obtained from Enterococcus bacteriophage 182 comprising at least a portion of a phage 182 ORF, preferably an inhibitory ORF, and more preferably at least a portion of one of the genes described above with anti-microbial activity. For example, ORF 002 encodes a DNA polymerase function. This polymerase may utilize host-derived accessory 30 proteins for its activity when replicating the phage template, sequestering such proteins from use by the bacterial polymerase, resulting in inhibition of DNA replication, cell division, and cell growth. Alternatively, ORFs 008 or 014 directly encode polypeptides with anti-microbial activity. ORF 008 is predicted to encode an WO 00/32825 PCT/IB99/02040 51 autolytic lysozyme, a protein known to have anti-microbial activity (Martin et al., 1998). ORF 014 likely encodes a holin function required for transit of the phage murein hydrolases to the periplasm. When the related product from Bacillus phage phi 29 (gene 14), was cloned in Escherichia coli, cell death ensued (Steiner et al., 1993). 5 Thus, production of proteins from Bacillus phage phi 29 gene 14 in E. coli resulted in cell death, whereas production of protein from Bacillus phage phi 29 gene 14 concomitantly with the phi 29 lysozyme or unrelated murein-degrading enzymes led to lysis, suggesting that membrane-bound protein 14 induces a nonspecific lesion in the cytoplasmic membrane (Steiner et al., 1993). 10 The present invention also provides the use of the Enterococcus bacteriophage 182 anti-microbial ORFs as pharmacological agents, either wholly or in part and derivatives, as well as the use of corresponding peptidomimetics, developed from amino acid or nucleotide sequence knowledge derived from Enterococcus bacteriophage 182 killer ORFs. This can be done where the structure of the 15 peptidomimetic compound corresponds to the structure of the active portion of a product of an ORF. In this analysis, the peptide backbone is transformed into a carbon based hydrophobic structure that can retain cytostatic or cytocidal activity for the bacterium. This is done by standard medicinal chemistry methods, measuring growth inhibition of the various molecules in liquid cultures or on solid medium. These 20 mimetics also represent lead compounds for the development of novel antibiotics. In this context, "corresponds" means that the peptidomimetic compound structure has sufficient similarities to the structure of the active portion of a product of one of the Enterococcus ORFs listed, that the peptidomimetic will interact with the same molecule as the product of the ORF, and preferably will elicit at least one cellular 25 response in common which relates to the inhibition of the cell by the phage protein. To validate the identity of an ORF as a killer ORF, it is preferably expressed in the host or other test bacterial organism and the effect of this expression on bacterial growth and replication is assessed. Therefore, all individual ORFs identified herein, e.g., those identified above, can be expressed, preferably overexpressed, in a 30 suitable host bacterium e.g., a host Enterococcus and the effect of this expression or overexpression on host metabolism and viability can be measured. Individual ORFs can be resynthesized from the phage genomic DNA by the polymerase chain reaction (PCR) using oligonucleotide primers flanking the ORF on WO 00/32825 PCT/IB99/02040 52 either side. Those skilled in the art are familiar with the design and synthesis of appropriate primer sequences. These single ORFs are preferably engineered so that they contain appropriate cloning sites at their extremities to allow their introduction into a new bacterial expression plasmid, allowing propagation in a standard bacterial 5 host such as E. coli, but containing the necessary information for plasmid replication in the target microbe, Enterococcus sp. (hereafter referred to as a shuttle vector). This shuttle vector also preferably contains regulatory sequences that allow inducible expression of the introduced ORF. As the candidate ORF may encode a killer function that will eliminate the host, it is highly advantageous that it not be 10 expressed (or at least not expressed at a substantial level) prior to testing for activity; thus screening for such sequences in a constitutive fashion is less likely to be successful (lethality). In an example presented in Fig. 7, regulatory sequences from the ars operon are used to direct individual ORF expression in Enterococcus. The ars operon encodes a series of proteins which normally mediate the extrusion of arsenite 15 and several other trivalent oxyanions from the cells when they are exposed to such toxic substances in their environment. The operon encoding this detoxifying mechanism is normally silent and only induced when arsenite-related compounds are present. Therefore, individual phage ORFs can be expressed in Enterococcus or other 20 suitable host in an inducible fashion by adding to the culture medium non-toxic arsenite concentrations during the growth of individual Enterococcus (or other host cells) clones expressing such individual phage ORFs. Toxicity of the phage killer ORF for the host is monitored by reduction or arrest of growth under induction conditions, as measured by optical density in liquid culture or after plating the 25 induced cultures on solid medium. Subsequently, interference of the phage ORF with the host biochemical pathways ultimately leading to reducing or arresting host metabolism can be measured by pulse chase experiments using radiolabeled precursors of either DNA replication, RNA transcription, or protein synthesis. Of course, other inducible regulatory sequences (e.g., promoters, operators, 30 etc.) may be used (e.g., systems using positive induction of expression or systems using release of repression). A variety of such systems are known to those-skilled in the art and can be utilized in the present invention.
WO 00/32825 PCT/IB99/02040 53 Nucleic acid sequences of the present invention can be isolated using a method similar to those described herein or other methods known to those skilled in the art. In addition, such nucleic acid sequences can be chemically synthesized by well known methods. Having the phage 182 ORFs, e.g., anti-bacterial ORFs of the present 5 invention, portions thereof, or oligonucleotides derived therefrom as described, other anti-microbial sequences from other bacteriophage sources can be identified and isolated using methods described here or other methods, including methods utilizing nucleic acid hybridization and/or computer-based sequence alignment methods. The invention also provides bacteriophage anti-microbial DNA segments from 10 other phages based on nucleic acids and sequences hybridizing to the presently identified inhibitory ORF under high stringency conditions or sequences which are highly homologous. The bacteriophage anti-microbial DNA segment from bacteriophage 182 can be used to identify a related segment from another unrelated phage based on stringent conditions of hybridization or on being a homolog based on 15 nucleic acid and/or amino acid sequence comparisons. As with the phage 182 inhibitory sequences, such homologous coding sequences and products can be used as antimicrobials, to construct active portions or derivatives, to construct peptidomimetics, and to identify bacterial targets. Enterococcus sequences are listed in Table 27 by accession number, providing 20 identification of possible targets of Enterococcus phage inhibitory ORF products, e.g., from phage 182. Streptococcus pneumoniae As indicated in the Summary above, the present invention is concerned 25 with the use of Streptococcus sp. bacteriophage Dp-1 coding sequences and the encoded polypeptides or RNA transcripts to identify bacterial targets for potential new antibacterial agents. Streptococcus pneumoniae is an important cause of community-acquired pneumonia and a major cause of otitis media, sinusitis, and meningitis in children and 30 adults. In Spain and other Mediterranean countries, the majority of S. pneumoniae are relatively resistant to penicillin (Klugman, 1990; Fenoll et al., 1991; Jorgenseret al., 1990). These strains also have decreased susceptibility to broad-spectrum cephaloporins, which are frequently used in the empiric treatment of meningitis and WO 00/32825 PCT/IB99/02040 54 other serious invasive bacterial infections. High-level resistance of pneumococci has been encountered in Hungary where 70% of children who were colonized with S. pneumoniae carried penicillin resistant strains that were also resistant to tetracycline, erythromycin, trimethoprim/sulfamethoxazole, and 30% resistant to chloramphenicol 5 (Neu, 1992). The resistance of pneumococci to macrolides such as erythromycin averages 20-25% in France, -20% in Japan, and <10% in Spain (Neu, 1992). The antimicrobial susceptibilities and distribution of serotypes of the 42 isolates of S. pneumoniae in southern Taiwan from invasive infections have been recently determined (Hseuh et al., 1996). Resistance rates among these isolates were: 10 erythromycin, 61.9%; clindamycin, 47.6%; chloramphenicol, 19%; and tetracycline, 73.8%. Resistance to three or more classes of antibiotics was found in 33.3% of the isolates. Bacteremic pneumonia and primary bacteremia accounted for 64.3% of the infections and mortality was 42.6%. Given the severity of these infections despite adequate antibiotic therapy, there is clearly a need for introduction of new therapeutic 15 options to prevent mortality due to invasive S. pneumoniae infections. Pneumococcal phages belong to four families and they present a great variety in morphology, including lytic and temperate phages (for a review, see Garcia et al., 1997). Examples of lytic phages are Cp-1 and Dp-1, whereas examples of temperate phages are HB-3, EJ-1, and HB-746. The complete nucleotide sequence and 20 functional organization of Cp-1 has been reported (Martin et al., 1996). Cp-1 has a 19,345 bp double-stranded DNA genome, with a terminal protein covalently linked to its 5' ends, that replicates by a protein primed mechanism. The phage contains 29 ORFs, 23 on one strand and 6 on the opposite. When these predicted proteins were compared to sequences compiled in GenBank EMBL databases, to ORFs showed 25 significant similarity to proteins of bacteriophage 29 that infects B. subtilis (Martin et al., 1996). The similar proteins corresponded to those involved in DNA replication (terminal protein and DNA polymerase), structural and morphogenic proteins (major head, collar, connector, tail, and encapsidation proteins), and proteins involved in lysis function (holin and lysozyme). In its strategy of lysis, the holin gene product inserts 30 itself into the cell membrane, allowing access of the lysozyme to the peptidoglycan. Expression of the Cp-1 holin protein in E. coli results in cell death after 2-hours of induction, but did not lead to lysis (Garcia et al., 1997). Cells harboring a plasmid construction with holin and lysozyme genes together did lyse after induction and the WO 00/32825 PCT/IB99/02040 55 viability loss was similar to that of the culture expressing holin alone. Cloning of these lytic genes in S. pneumoniae showed that both genes had the same effect as in E. coli. That is, holin itself did not lyse the culture but the viability loss was noticeable, whereas both holin and lysozyme together were capable of lysing M31, an amidase 5 deleted mutant (Garcia et al., 1997). Recently, a small portion (-4 kbp) of a second S. pneumoniae phage, Dp-1, has been sequenced (Sheehan et al., 1997). This portion contains the genes coding for the lytic system (Sheehan et al., 1997) and shows a modular organization similar to that described for Cp-1. However, in this case, a single chimeric protein appears to be 10 made in which the N-terminal domain is highly similar to that of the murein hydrolase coded by a gene found in the phage BK5-T that infects Lactococcus lactis, and the C terminal domain is homologous to holins. Thus, both functions appear to have been combined in a novel chimeric protein. Bacteriophage Dp-1 was obtained from Dr. P. Garcia (Departamento de 15 Microbiologia Molecular, Centro de Departamento de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Velazquez, Madrid, Spain). We found that Dp-1 has a double-stranded DNA genome of 56,506 bp, predicted to encode 85 ORFs greater than 33 amino acids and with upstream Shine-Dalgarno motifs for translation initiation (Tables 28 & 30, and Fig. 6). Computational analysis 20 of the predicted protein products of Streptococcus bacteriophage Dp-1 protein products, which detected homologs in public databases, are listed inTable 31, along with the accompanying list of related proteins. From this analysis, it is apparent that several predicted genes of Dp-1 encode polypeptides that are related to structural proteins. ORFs 001, 002, 004, and 030 are 25 predicted to encode tail proteins, minor structural proteins, and minor capsid proteins (Table 31). We also note the identification of several gene products that are likely involved in DNA synthesis. These include ORF 3 which encodes DNA polymerase, ORF 8 which encodes a SWI/SNF helicase-related protein, ORF 10 encodes a protein showing homology to recA, and ORF 13 encodes a dnaZX-like ORE. 30 In E. coli, RapA encodes an RNA polymerase (RNAP)-associated protein with ATPase activity and which is a homolog of the eukaryotic SWI/SNF family, a set of proteins whose members are involved are involved in transcription activation, nucleosome remodeling, and DNA repair. RapA forms a stable complex with RNAP, WO 00/32825 PCT/IB99/02040 56 as if it were a subunit of RNAP and it is possible that the ORF 8 product behaves similarly or in a dominant-negative fashion to inhibit the activity of RapA. Mutation of the essential E. coli dnaZX results in a block in DNA chain elongation during replication (Maki et al., 1988). The dnaZX gene has only one open reading frame for 5 a 71-kDa polypeptide from which the two distinct DNA polymerase III holoenzyme subunits, tau (71 kDa) and gamma (47 kDa), are produced. The tau subunit is the precursor of the gamma subunit, and the gamma subunit is produced by a -1 frameshift causing early termination of translation (Tsuchihashi et al., 1990). These proteins show single-strand DNA binding properties that is ATPase (and dATPase) 10 dependent and are thought to increasing the processivity of the core DNA polymerase enzyme (Lee et al., 1987). There are several Dp- 1 ORFs which encode proteins predicted to play a role in cellular metabolic pathways. These include polypeptides involved in coenzyme PQQ synthesis (ORFs 20, 29, 38). Pyrrolo-quinoline quinone (PQQ) is the non-covalently 15 bound prosthetic group of many quinoproteins catalysing reactions in the periplasm of Gram-negative bacteria. Most of these involve the oxidation of alcohols or aldose sugars. Interestingly, ORFs 20, 29, and 30 also show homology to the exoenzyme S regulon (Frank, 1997). Proteins encoded by the P. aeruginosa exoenzyme S regulon may be involved in a contact-mediated translocation mechanism to transfer anti-host 20 factors directly into eukaryotic cells disrupting eukaryotic signal transduction through ADP-ribosylation (Frank, 1997). There is also a protein with similarity to GTP cyclohydrolase I (ORF 21) and ORF 41 which shows homology to dUTPase (Table 31). GTP cyclohydrolase I is an enzyme that catalyzes the first reaction in the pathway for the biosynthesis of the 25 pteridine, a cofactor of the monooxygenases of the aromatic amino acids. Disruption of the homologous gene in Saccharomyces cerevisiae leads to a recessive conditional lethality due to folinic acid auxotrophy, that can be complemented with the mammalian or bacterial GTP cyclohydrolase I enzymes (Nardese et al., 1996; Mancini et al., 1999). 30 ORF 16 shows high homology to autolysin. This region of the phage sequence was previously reported (Sheehan et al., 1997) and encompasses - 4 kbp of our sequence. The sequence published by (Sheehan et al., 1997) is shown in Table 32. Thus, the present invention provides a nucleic acid sequence obtained from Streptococcus bacteriophage Dp-1 comprising at least a portion of a phage Dp-1 ORF; 35 preferably an inhibitory ORF, and more preferably at least a portion of 6ne of the genes described above with anti-microbial activity. For example, ORF 013 encodes a WO 00/32825 PCT/IB99/02040 57 protein with homology to the gamma subunit of DNA polymerase (dnaX gene). This protein may act in a dominant-negative fashion to sequester the host DNA polymerase for its own replication, thus inhibiting host DNA replication. The dnaX gene product is essential for E. coli replication (Kodaira et al., 1983). 5 In certain preferred embodiments of the present invention, the bacterial target of a bacteriophage inhibitor ORF product, e.g., an inhibitory protein or polypeptide, is encoded by a Streptococcus nucleic acid coding sequence from a host bacterium for bacteriophage Dp-1. As above, possible target sequences are described herein by reference to sequence source sites. The sequence encoding the target preferably 10 corresponds to a Streptococcus nucleic acid sequence available from The Institute for Genomic Research (TIGR), or available from GenBank or other public database. The TIGR Streptococcus sequences are publicly available at The Institute for Genomics Research at URL: http://www.tier.org The amino acid sequence of a polypeptide target is readily provided by 15 translating the corresponding coding region. For the sake of brevity, the sequences are not reproduced herein. Also, in preferred embodiments, a target sequence corresponds to a Streptococcus pneumoniae coding sequences corresponding to a sequence listed in Table 33 herein. Sequences for other Streptococcal species are also available from TIGR and./or from GenBank. The listing in Table 33 describes 20 Streptococcus sequences currently deposited in GenBank. Again, for the sake of brevity, the sequences are described by reference to the GenBank entries instead of being written out in full herein. In cases where the TIGR or GenBank entry for a coding region is not complete, the complete sequence can be readily obtained by routine methods, e.g., by isolating a clone in a phage Dp-1 host Streptococcus sp. 25 genomic library, and sequencing the clone insert to provide the relevant coding region. The boundaries of the coding region can be identified by conventional sequence analysis and/or by expression in a bacterium in which the endogenous copy of the coding region has been inactivated and using subcloning to identify the functional start and stop codons for the coding region. 30 In the various aspects of this invention involving Dp-1 sequences, preferably the sequence is preferably not contained in the sequence described in Sheehan et al., 1997 (Table 32). Validatine Identified Inhibitory Phage ORFs 35 A fifth step involves validating the identified phage inhibitor ORF by independent methods, and delineating further possible smaller segments of the ORFs WO 00/32825 PCT/IB99/02040 58 that have inhibitory activity. Several methods exist to validate the role of the identified ORF as an inhibitor ORF. One example utilizes the creation of a mutant variant of the phage ORF in which the candidate ORF carries a partial or complete loss-of-function mutation that 5 is measurable as compared with the non-mutant ORF. Comparison of the effects of expression of the loss of function mutant with the normal ORF provides confirmation of the identification of an inhibitor ORF where the loss-of-function mutant provides a measurably lower level of inhibition, preferably no inhibition. The loss of function may be conditional, e.g., temperature sensitive. 10 Once validation of the inhibitor ORF is achieved, a bi-directional deletion analysis can be carried out using the same experimental system to identify the minimal polypeptide segment that has inhibitor activity. This may be carried out by a variety of means, e.g., by exonuclease or PCR methodologies, and is used to determine if a relatively small segment of the ORF (i.e., the product of the ORF) still 15 possesses inhibitory activity when isolated away from its native sequence. If so, a portion of the ORF encoding this "active portion" can be used as a template for the synthesis of novel anti-microbial agents and further allowing derivation of the peptide sequence, e.g., using modified peptides and/or peptidomimetics. In creation of certain peptidomimetics, the peptide backbone is transformed 20 into a carbon-based hydrophobic structure that can retain inhibitor activity against the bacterium. This is done by standard medicinal chemistry methods, typically monitored by measuring growth inhibition of the various molecules in liquid cultures or on solid medium. These mimetics can also represent lead compounds for the development of novel antibiotics. 25 Recently, a major effort has been undertaken by the pharmaceutical industry and their biotechnology partners for the sequencing of bacterial pathogen genomes. The rationale is that the systematic sequencing of the genome will identify all of the bacterial proteins and therefore this proteome will be the target for designing novel inhibitor antibiotics. Although systematic, this approach has several major problems. 30 The first is that analysis of primary amino acid sequences of bacterial proteins does not immediately reveal which protein will be essential for viability of the bacterium, and target validation is thus a major issue. The second problem is one of redundancy, as several biochemical pathways are either structurally duplicated in bacteria (different isoforms of the same enzyme), or functionally duplicated by the presence of 35 salvage pathways in the event of a metabolic block in one pathway (different. nutritional conditions). The third is that even a valid target may not be structurally or WO 00/32825 PCT/IB99/02040 59 functionally amenable to inhibition by small molecules because of inaccessibility (sequestration of target). Therefore, there is considerable interest within the pharmaceutical and biotechnology industry in identifying key targets for drug discovery amongst the mass 5 of novel targets generated by large-scale genomic sequencing projects. On the other hand, and underscoring the instant invention, the phages herein described have, over millions of years, evolved specific mechanisms to target such key biochemical pathways and proteins. In the few cases where inhibition by phages has been elucidated (e.g., see ref. 3), such bacterial targets are invariably rate-limiting 10 in their respective biochemical pathways, are not redundant, and/or are readily accessible for inhibition by the phage (or by another inhibitory compound). Therefore, the sixth step of this invention involves identifying the host biochemical pathways and proteins that are targeted by the phage inhibitory mechanisms. 15 Identifying, Validating, and Characterizing Bacterial Host Target Proteins and Affected Pathways A rationale for this step is that the inhibitor ORF product from the phage physically interacts with and/or modifies certain microbial host components to block their function. Exemplary approaches which can be used to identify the host bacterial 20 pathways and proteins that interact with, and preferably also are inhibited by, phage ORF product(s) are described below. One approach is a genetic screen to determine physiological protein:protein interaction, for example, using a yeast two hybrid system. In this assay, the phage ORF is fused to the carboxyl terminus of the yeast Gal4 activation domain II (amino 25 acids 768-88 1) to create a bait vector. A cDNA library of cloned S. aureus sequences which have been engineered into a plasmid where the S. aureus sequences are fused to the DNA binding domain of Gal4 is also generated. These plasmids are introduced alone, or in combination, into yeast strain Y 190 - previously engineered with chromosomally integrated copies of the E. coli lacZ and the selectable HIS3 genes, 30 both under Gal4 regulation (Durfee, T., Becherer, K., Chen, P.-L., Yeh, S.-H., Yang, Y., Kilbum, A.E., Lee, W.-H., and Elledge, S.J. (1993). Genes & Dev. 7, 555-569). If the two proteins expressed in yeast interact, the resulting complex will activate transcription from promoters containing Gal4 binding sites. A lacZ and His3 gene, each driven by a promoter containing Gal4 binding sites, have been integrated into the 35 genome of the host yeast system used for measuring protein-protein interacti-ens. Such a system provides a physiological environment in which to detect potential protein interactions. This system has been extensively used to identify novel protein-protein WO 00/32825 PCT/IB99/02040 60 interaction partners and to map the sites required for interaction (for example, to identify interacting partners of translation factors (Qiu, H., Garcia-Barrio, M.T., and Hinnebusch, A.G. (1998). Mol & Cell Biology 18, 2697-2711), transcription factors (Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura ,Y., and 5 Miki, Y. (1998). Genes, Chromosomes & Cancer 21, 217-222), and proteins involved in signal transduction (Endo, T.A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., and Yoshimura, A. Nature. 387, 921-924). This approach has also been used in many 10 published reports to identify interaction between mammalian viral and mammalian cell proteins. For example, the non-structural protein NS 1 of parvovirus is essential for viral DNA amplification and gene expression and is also the major cytopathic effector of these viruses. A yeast two-hybrid screen with NS 1 identified a novel cellular protein 15 of unknown function that interacts with NS-1, called SGT, for small glutamine-rich tetratricopeptide repeat (TPR)-containing protein (Cziepluch C. Kordes E. Poirey R. Grewenig A. Rommelaere, J, and Jauniaux JC. (1998) J Virol. 72, 4149-4156). In another screen, the adenovirus E3 protein was recently shown to interact with a novel tumor necrosis factor alpha-inducible protein and to modulate some of the activities of 20 E3 (Li Y. Kang J. and Horwitz M.S. (1998). Mol & Cell Biol. 18, 1601-1610). In yet another recent screen, the herpes simplex virus 1 alpha regulatory protein ICPO was found to interact with (and stabilize) the cell cycle regulator cyclin D3 (Kawaguchi Y. Van Sant C. and Roizman B. (1997). J Virol. 71,7328-7336). Another two-hybrid system for identifying protein:protein interactions is 25 commercially available from STRATEGENE T M as the CYTO-TRAP TM system (Chang et al., Strategies Newsletter 11(3), 65-68 (1998)(from Stratagene)). The system is a yeast-based method for detecting protein:protein interactions in vivo, using activation of the Ras signal transduction cascade by localizing a signal pathway component, human Sos (hSos), to its activation site in the yeast plasma membrane. 30 The system uses a temperature-sensitive Saccharomyces cerevisiae mutant, strain cdc25H, which contains a point mutation at amino acid residue 1328 of the cdc25 gene. This gene encodes a guanyl nucleotide exchange factor which binds and activates Ras, leading to cell growth. The mutation in the cdc25 gene prevents host growth at 37*C, but at a permissive temperature of 25 0 C, growth is normal. The 35 system utilizes the ability of (hSos) to complement the cdc25 defect and activate fhe yeast Ras signaling pathway. Once (hSos) is expressed and localized to the plasma membrane, the cdc25H yeast strain grows at 37 0 C. Localizing hSos to the plasma WO 00/32825 PCT/IB99/02040 61 membrane occurs through a protein:protein interaction. A protein of interest, or bait, is expressed as a fusion protein with hSos. The library, or target proteins are expressed with the myristylation membrane-localization signal. The yeast cells are then incubated under restrictive conditions (37*C). If the bait and the target protein 5 interact, the hSos protein is recruited to the membrane, activating the Ras signaling pathway and allowing the cdc25H yeast strain to grow at the restrictive temperature. The protein targets of phage inhibitory ORFs can also be identified using bacterial genetic screens. One approach involves the overexpression of a phage inhibitory protein in mutagenized bacterial host species, followed by plating the cells 10 and searching for colonies that can survive the antimicrobial activity of the inhibitory ORF. These colonies are then grown, their DNA extracted, and cloned into an expression vector that contains a replicon of a different incompatibility group from the plasmid expressing the original ORF. This library is then introduced into a wild type host bacterium in conjunction with an expression vector driving synthesis of the 15 phage ORF, followed by selection for surviving bacteria. Thus, bacterial DNA fragments from the survivors presumably contain a DNA fragment from the original mutagenized host bacterial genome that can protect the cell from the antimicrobial activity of the inhibitory phage ORF. This fragment can be sequenced and compared with that of the bacterial host to determine in which gene the mutation lies. This 20 approach enables one to determine the targets and pathways that are affected by the killing function. A second approach is based on identifying protein:protein interactions between the phage ORF product and bacterial S. aureus, e.g., proteins using a biochemical approach based, for example, on affinity chromatography. This approach 25 has been used, for example, to identify interactions between lambda phage proteins and proteins from their E. coli host (Sopta, M., Carthew, R.W., and Greenblatt, J. (1985) J. Biol. Chem. 260, 10353-10369). The phage ORF is fused to a peptide tag (e.g. glutathione-S-transferase ("GST"), 6xHIS, ("HIS") and/or calmodulin binding protein ("CPB")) within a commercially available plasmid vector that directs high 30 level expression on induction of a suitably responsive promoter driving the fusion's expression. The translated fusion protein is expressed in E. coli, purified, and immobilized on a solid phase matrix via, for example the tag. Total cell extracts from the host bacterium, e.g., S. aureus, are then passed through the affinity matrix containing the immobilized phage ORF fusion protein; host proteins retained on the 35 column are then eluted under different conditions of ionic strength, pH, detergeii~s etc., and characterized by gel electrophoresis and other techniques. Appropriate controls are run to guard against nonspecific binding to the resin. Target proteins thus WO 00/32825 PCT/IB99/02040 62 recovered should be enriched for the phage protein/peptide of interest and are subsequently electrophoretically or otherwise separated, purified, sequenced, or biochemically analyzed. Usually sequencing entails individual digestion of the proteins to completion with a protease (e.g. -trypsin), followed by molecular mass and 5 amino acid composition and sequence determination using, for example, mass spectrometry, e.g., by MALDI-TOF technology (Qin, J., Fenyo, D., Zhao, Y., Hall, W.W., Chao, D.M., Wilson, C.J., Young, R.A. and Chait, B.T. (1997). Anal. Chem. 69, 3995-4001). The sequence of the individual peptides from a single protein are then 10 analyzed by the bioinformatics approach described above to identify the S. aureus protein interacting with the phage ORE. This analysis is performed by a computer search of the S. aureus genome for an identified sequence. Alternatively, all tryptic peptide fragments of the S. aureus genome can be predicted by computer software, and the molecular mass of such fragments compared to the molecular mass of the 15 peptides obtained from each interacting protein eluted from the affinity matrix. The responsible gene sequence can be obtained, for example by using synthetic degenerate nucleic acid sequences to pull out the corresponding homologous bacterial sequence. Alternatively, antibodies can be generated against the peptide and used to isolate nascent peptide/mRNA transcript complexes, from which the mRNA can be reverse 20 transcribed, cloned, and further characterized using the procedures discussed herein. A variety of other binding assay methods are known in the art and can be used to identify interactions between phage proteins and bacterial proteins or other bacterial cell components. Such methods that allow or provide identification of the bacterial component can be used in this invention for identifying putative targets. 25 Validation of the interaction between the phage ORF product and the bacterial proteins or other components can be obtained by a second independent assay (e.g., co-immunoprecipitation or protein-protein crosslinking experiments (Qiu, H., Garcia Barrio, M.T., and Hinnebusch, A.G. (1998). Mol & Cell Biology 18, 2697-2711; Brown, S. and Blumenthal, T. (1976). Proc. Nati. Acad. Sci. USA 73, 1131-1135)). 30 Finally, the essential nature of the identified bacterial proteins is preferably determined genetically by creating a constitutive or inducible partial or complete loss of-function mutation in the gene encoding the identified interacting bacterial protein. This mutant is then tested for bacterial survival and replication. The protein target of the phage inhibitor function can also be identified using a., 35 genetic approach. Two exemplary approaches will be delineated here. The fixsV approach involves the overexpression of a predetermined phage inhibitor protein in mutagenized host bacteria, e.g., S. aureus, followed by plating the cells and searching WO 00/32825 PCT/IB99/02040 63 for colonies that can survive the inhibitor. These colonies will then be grown, their DNA extracted and cloned into an expression vector that contains a replicon of a different incompatibility group, and preferably having a different selectible marker than the plasmid expressing the phage inhibitor. Thus, host DNA fragments from the 5 mutant that can protect the cell from phage ORF inhibition can be sequenced and compared with that of the bacterial host to determine in which gene the mutation lies. This approach allows rapid determination of the targets and pathways that are affected by the inhibitor. Alternatively, the bacterial targets can be determined in the absence of 10 selecting for mutations using an approach known as "multicopy suppression". In this approach, the DNA from the wild type host is cloned into an expression vector that can coexist, as previously described, with one containing a predetermined phage inhibitor. Those plasmids that contain host DNA fragments and genes that protect the host from the phage inhibitor can then be isolated and sequenced to identify putative 15 targets and pathways in the host bacteria. Regardless of the specific mode of identification, screening assays may additionally utilize gene fusions to specific "reporter genes" to identify a bacterial gene(s) whose expression is affected when the host target pathway is affected by the phage inhibitor. Such gene fusions can be used to search a number of small molecule 20 compounds for inhibitors that may affect this pathway and thus cause cell inhibition. This approach will allow the screening of a large number of molecules on petri dishes or 96-well format by monitoring for a simple color change in the bacterial colonies. In this manner, we can validate host targets and classes of compounds for further study and clinical development. These inhibitors also represent lead compounds for 25 the development of other antibiotics. Bioinformatics and comparative genomics are preferably then applied to the identified bacterial gene products to predict biochemical function. The biochemical activity of the protein can be verified in vitro in cell free assays or in vivo in intact cells. In vitro biochemical assays utilizing cell-free extracts or purified protein are 30 established as a basis for the screening and development of inhibitors. These inhibitors, preferably small molecule inhibitors, may comprise peptides, antibodies, products from natural sources such as fungal or plant extracts or small molecule organic compounds. In general, small molecule organic compounds are preferred. These compounds may, for example, be identified within large compound . 35 libraries, including combinatorial libraries. For example, a plurality of compoliids, preferably a large number of compounds can be screened to determine whether any of the compounds binds or otherwise disrupts or inhibits the identified bacterial target.
WO 00/32825 PCT/IB99/02040 64 Compounds identified as having any of these activities can then be evaluated further in cell culture and/or animal model systems to determine the pharmacological properties of the compound, including the specific anti-microbial ability of the compound. 5 For mixtures of natural products, including crude preparations, once a preparation or fraction of a preparation is shown the have an anti-microbial activity, the active substance can be isolated and identified using techniques well known in the art, if the compound is not already available in a purified form. Identified compounds possessing anti-microbial activity and similar 10 compounds having structural similarity can be further evaluated and, if necessary, derivatized according to synthesis and/or modification methods available in the art selected as appropriate for the particular starting molecule. Derivatization of identified anti-microbials 15 In cases where the identified anti-microbials above might represent peptidal compunds, the in vivo effectiveness of such compounds may be advantageously enhanced by chemical modification using the natural polypeptide as a starting point and incorporating changes that provide advantages for use, for example, increased stability to proteolytic degradation, reduced antigenicity, improved tissue penetration, 20 and/or improved delivery characteristics. In addition to active modifications and derivative creations, it can also be useful to provide inactive modifications or derivatives for use as negative controls or introduction of immunologic tolerance. For example, a biologically inactive derivative which has essentially the same epitopes as the corresponding natural 25 antimicrobial can be used to induce immunological tolerance in a patient being treated. The induction of tolerance can then allow uninterrupted treatment with the active anti-microbial to continue for a significantly longer period of time. Modified anti-microbial polypeptides and derivatives can be produced using a number of different types of modifications to the amino acid chain. Many such 30 methods are known to those skilled in the art. The changes can include, for example, reduction of the size of the molecule, and/or the modification of the amino acid sequence of the molecule. In addition, a variety of different chemical modifications of the naturally occurring polypeptide can be used, either with or without modifications to the amino acid sequence or size of the molecule. Such chemical modifications can, 35 for example, include the incorporation of modified or non-natural amino acids ornoh amino acid moieties during synthesis of the peptide chain, or the post-synthesis modification of incorporated chain moieties.
WO 00/32825 PCT/IB99/02040 65 The oligopeptides of this invention can be synthesized chemically or through an appropriate gene expression system. Synthetic peptides can include both naturally occurring amino acids and laboratory synthesized, modified amino acids. Also provided herein are functional derivatives of anti-microbial proteins or 5 polypeptides. By "functional derivative" is meant a "chemical derivative," "fragment," "variant," "chimera," or "hybrid" of the polypeptide or protein, which terms are defined below. A functional derivative retains at least a portion of the function of the protein, for example reactivity with a specific antibody, enzymatic activity or binding activity. 10 A "chemical derivative" of the complex contains additional chemical moieties not normally a part of the protein or peptide. Such moieties may improve the molecule's solubility, absorption, biological half-life, and the like. The moieties may alternatively decrease the toxicity of the molecule, eliminate or attenuate any undesirable side effect of the molecule, and the like. Moieties capable of mediating 15 such effects are disclosed in Alfonso and Gennaro (1995). Procedures for coupling such moieties to a molecule are well known in the art. Covalent modifications of the protein or peptides are included within the scope of this invention. Such modifications may be introduced into the molecule by reacting targeted amino acid residues of the peptide with an organic derivatizing agent that is capable of reacting 20 with selected side chains or terminal residues, as described below. Cysteinyl residues most commonly are reacted with alpha-haloacetates (and corresponding amines), such as chloroacetic acid or chloroacetamide, to give carboxymethyl or carboxyamidomethyl derivatives. Cysteinyl residues also are derivatized by reaction with bromotrifluoroacetone, chloroacetyl phosphate, N 25 alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl 2-pyridyl disulfide, p-chloro mercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa-1,3 diazole. Histidyl residues are derivatized by reaction with diethylprocarbonate at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain. Para 30 bromophenacyl bromide also is useful; the reaction is preferably performed in 0.1 M sodium cacodylate at pH 6.0. Lysinyl and amino terminal residues are reacted with succinic or other carboxylic acid anhydrides. Derivatization with these agents has the effect of reversing the charge of the lysinyl residues. Other suitable reagents for derivatizing 35 primary amine- containing residues include imidoesters such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; WO 00/32825 PCT/IB99/02040 66 trinitrobenzenesulfonic acid; O-methylisourea; 2,4 pentanedione; and transaminase catalyzed reaction with glyoxylate. Arginyl residues are modified by reaction with one or several conventional reagents, among them phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione, and 5 ninhydrin. Derivatization of arginine residues requires that the reaction be performed in alkaline conditions because of the high pKa of the guanidine functional group. Furthermore, these reagents may react with the groups of lysine as well as the arginine alpha-amino group. Tyrosyl residues are well-known targets of modification for introduction of 10 spectral labels by reaction with aromatic diazonium compounds or tetranitromethane. Most commonly, N-acetylimidizol and tetranitromethane are used to form 0-acetyl tyrosyl species and 3-nitro derivatives, respectively. Carboxyl side groups (aspartyl or glutamyl) are selectively modified by reaction carbodiimide (R'-N-C-N-R') such as 1-cyclohexyl-3-(2-morpholinyl(4-ethyl) 15 carbodiimide or 1-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide. Furthermore, aspartyl and glutamyl residues are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions. Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues are 20 deamidated under mildly acidic conditions. Either form of these residues falls within the scope of this invention. Derivatization with bifunctional agents is useful, for example, for cross linking component peptides to each other or the complex to a water-insoluble support matrix or to other macromolecular carriers. Commonly used cross-linking agents 25 include, for example, 1,1-bis (diazoacetyl)-2-phenylethane, glutaraldehyde, N hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobi functional imidoesters, including disuccinimidyl esters such as 3,3' dithiobis(succinimidylpropionate), and bifunctional maleimides such as bis-N maleimido-1,8-octane. Derivatizing agents such as methyl-3-[p-azidophenyl) 30 dithiolpropioimidate yield photoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbohydrates and the reactive substrates described in U.S. Patent Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440 are employed for protein immobilization. 35 Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains (Creighton, T.E., WO 00/32825 PCT/IB99/02040 67 Proteins: Structure and Molecular Properties, W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)), acetylation of the N-terminal amine, and, in some instances, amidation of the C-terminal carboxyl groups. Such derivatized moieties may improve the stability, solubility, absorption, 5 biological half life, and the like. The moieties may alternatively eliminate or attenuate any undesirable side effect of the protein complex. Moieties capable of mediating such effects are disclosed, for example, in Alfonso and Gennaro (1995). The term "fragment" is used to indicate a polypeptide derived from the amino acid sequence of the protein or polypeptide having a length less than the full-length 10 polypeptide from which it has been derived. Such a fragment may, for example, be produced by proteolytic cleavage of the full-length protein. Preferably, the fragment is obtained recombinantly by appropriately modifying the DNA sequence encoding the proteins to delete one or more amino acids at one or more sites of the C-terminus, N-terminus, and/or within the native sequence. 15 Another functional derivative intended to be within the scope of the present invention is a "variant" polypeptide that either lacks one or more amino acids or contains additional or substituted amino acids relative to the native polypeptide. The variant may be derived from a naturally occurring polypeptide by appropriately modifying the protein DNA coding sequence to add, remove, and/or to modify codons 20 for one or more amino acids at one or more sites of the C-terminus, N-terminus, and/or within the native sequence. A functional derivative of a protein or polypeptide with deleted, inserted and/or substituted amino acid residues may be prepared using standard techniques well-known to those of ordinary skill in the art. For example, the modified 25 components of the functional derivatives may be produced using site-directed mutagenesis techniques (as exemplified by Adelman et al., 1983, DNA 2:183; Sambrook et al., 1989) wherein nucleotides in the DNA coding sequence are modified such that a modified coding sequence is produced, and thereafter expressing this recombinant DNA in a prokaryotic or eukaryotic host cell, using techniques such as 30 those described above. Alternatively, components of functional derivatives of complexes with amino acid deletions, insertions and/or substitutions may be conveniently prepared by direct chemical synthesis, using methods well-known in the art. Insofar as other anti-microbial inhibitor compounds identified by the invention 35 described herein may not be peptidal in nature, other chemical techniques existto allow their suitable modification, as well, and according the desirable principles discussed above.
WO 00/32825 PCT/IB99/02040 68 Administration and Pharmaceutical Compositions For the therapeutic and prophylactic treatment of infection, the preferred method of preparation or administration of anti-microbial compounds will generally 5 vary depending on the precise identity and nature of the anti-microbial being delivered. Thus, those skilled in the art will understand that administration methods known in the art will also be appropriate for the compounds of this invention. The particularly desired anti-microbial can be administered to a patient either by itself, or in pharmaceutical compositions where it is mixed with suitable carriers or 10 excipient(s). In treating an infection, a therapeutically effective amount of an agent or agents is administered. A therapeutically effective dose refers to that amount of the compound that results in amelioration of one or more symptoms of bacterial infection and/or a prolongation of patient survival or patient comfort. Toxicity, therapeutic and prophylactic efficacy of anti-microbials can be 15 determined by standard pharmaceutical procedures in cell cultures and/or experimental organisms such as animals, e.g., for determining the LD 5 0 (the dose lethal to 50% of the population) and the EDO (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD 5 0
/ED
50 . Compounds that 20 exhibit large therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED 5 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route 25 of administration utilized. For any compound identified and used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. Such information can be used to more accurately determine useful doses in organisms such as plants and animals, preferably mammals, and most preferably humans. Levels in 30 plasma may be measured, for example, by HPLC or other means appropriate for detection of the particular compound. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition (see e.g. Fingl et. al., in The Pharmacological Basis of Therapeutics, 1975, Ch. 1 p.1). 35 It should be noted that the attending physician would know how and wheii to terminate, interrupt, or adjust administration due to toxicity, organ dysfunction, or other systemic malady. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding WO 00/32825 PCT/IB99/02040 69 toxicity). The magnitude of an administered dose in the management of the disorder of interest will vary with the severity of the condition to be treated and the route of administration. The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose 5 frequency, will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above also may be used in veterinary or phyto medicine. Depending on the specific infection target being treated and the method selected, such agents may be formulated and administered systemically or locally, i.e., 10 topically. Techniques for formulation and administration may be found in Alfonso and Gennaro (1995). Suitable routes may include , for example, oral, rectal, transdermal, vaginal, transmucosal, intestinal, parenteral, intramuscular, subcutaneous, or intramedullary injections, as well as intrathecal, intravenous, or intraperitoneal injections. 15 For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art. 20 Use of pharmaceutically acceptable carriers to formulate identified anti microbials of the present invention into dosages suitable for systemic administration is within the scope of the invention. With proper choice of carrier and suitable manufacturing practice, the compositions of the present invention, in particular those formulated as solutions, may be administered parenterally, such as by intravenous 25 injection. Appropriate compounds can be formulated readily using pharmaceutically acceptable carriers well known in the art into dosages suitable for oral administration. Such carriers enable the compounds of the invention to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. 30 Agents intended to be administered intracellularly may be administered using techniques well known to those of ordinary skill in the art. For example, such agents may be encapsulated into liposomes, then administered as described above. Liposomes are spherical lipid bilayers with aqueous interiors. All molecules present in an aqueous solution at the time of liposome formation are incorporated into the . 35 aqueous interior. The liposomal contents are both protected from the external microenvironment and, because liposomes fuse with cell membranes, are efficiently WO 00/32825 PCT/IB99/02040 70 delivered into the cell cytoplasm. Additionally, due to their hydrophobicity, small organic molecules may be directly administered intracellularly. Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to 5 achieve the intended purpose. Determination of the effective amounts is well within the capability of those skilled in the art. In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations 10 which can be used pharmaceutically. The preparations formulated for oral administration may be in the form of tablets, dragees, capsules, or solutions, including those formulated for delayed release or only to be released when the pharmaceutical reaches the small or large intestine. The pharmaceutical compositions of the present invention may be 15 manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levitating, emulsifying, encapsulating, entrapping or lyophilizing processes. Pharmaceutical formulations for parenteral administration include aqueous solutions of the active anti-microbial compounds in water-soluble form. 20 Alternatively, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or 25 dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Pharmaceutical preparations for oral use can be obtained by combining the active compounds with solid excipient, optionally grinding a resulting mixture, and 30 processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium 35 carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
WO 00/32825 PCT/IB99/02040 71 Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. 5 Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active 10 ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. 15 The above methodologies may be employed either actively or prophylactically against an infection of interest. Computer-related Aspects and Embodiments In addition to the provision of compounds as chemical entities, nucleotide 20 sequences, or fragments thereof at least 95%, preferably at least 97%, more preferably at least 99%, and most preferably at least 99.9% identical to phage inhibitor sequences can also be provided in a variety of additional media to facilitate various uses. Thus, as used in this section, "provided" refers to an article of manufacture, rather than an actual nucleic acid molecule, which contains a nucleotide sequence of 25 the present invention; e.g., a nucleotide sequence of an exemplary bacteriophage or a sequence encoding a bacterial target or a fragment thereof, preferably a nucleotide sequence at least 95%, more preferably at least 99% and most preferably at least 99.9% identical to such a bacteriophage or bacterial sequence, for example, to a polynucleotide of an unsequenced phage listed in Table 1, preferably of bacteriophage 30 77 (S. aureus host) or bacteriophage 3A (S.aureus host) or bacteriophage 96 (S. aureus host). Such an article provides a large portion of the particular bacteriophage genome or bacterial gene and parts thereof (e.g., a bacteriophage open reading frame (ORF)) in a form which allows a skilled artisan to examine and/or analyze the sequence using means not directly applicable to examining the actual genome or gene 35 or subset thereof as it exists in nature or in purified form as a chemical entity, In one application of this aspect, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, "computer WO 00/32825 PCT/IB99/02040 72 readable media" refers to any medium that can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these 5 categories, such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create an article of manufacture which includes one or more computer readable media having recorded thereon a nucleotide sequence or sequences of the present invention. Likewise, it will be clear to those of skill how additional computer 10 readable media that may be developed also can be used to create analogous manufactures having recorded thereon a nucleotide sequence of the present invention. As used herein, "recorded" refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently known methods for recording information on computer readable medium to generate 15 manufactures comprising the nucleotide sequence information of the present invention. A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be 20 based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can, for example, be presented in a word processing test file, formatted in commercially available software such as WordPerfect and Microsoft Word, or 25 represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data processor structuring formats (e.g., text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention. 30 Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. Thus, by providing in computer readable form a nucleotide sequence of an unsequenced bacteriophage, such as an exemplary bacteriophage listed in Table 1 or of a sequence encoding a bacterial target or a fragment thereof, preferably a nucleotide sequence at 35 least 95%, more preferably at least 99% and most preferably at least 99.9% identical to such a bacteriophage or bacterial sequence, for example, to a polynucleotide of bacteriophage 77 (S. aureus host) or bacteriophage 3A (S.aureus host) bacteriophage WO 00/32825 PCT/IB99/02040 73 96 (S. aureus host), bacteriophage 44AHJD (S. aureus host), bacteriophage Dp-1 (Streptococcus pneumoniae host), or bacteriophage 182 (Enterococcus host) the present invention enables the skilled artisan to routinely access the provided sequence information for a wide variety of purposes. 5 Those skilled in the art understand that software can implement a variety of different search or analysis software which implement sequence search and analysis algorithms, e.g., the BLAST (Altschul et al., J. Mol. Biol. 215:403410 (1990) and BLAZE (Brutlag et al., Comp. Chem 17:203-207 (1993)) search algorithms. For example, such search algorithms can be implemented on a Sybase system and used to 10 identify open reading frames (ORFs) within the bacteriophage genome which contain homology to ORFs or proteins from other viruses, e.g, other bacteriophage, and other organisms, e.g., the host bacterium. Among the ORFs discussed herein are protein encoding fragments of the bacteriophage genomes which encode bacteria-inhibiting proteins or fragments. 15 The present invention further provides systems, particularly computer-based systems, which contain the sequence information described. Such systems are designed to identify, among other things, useful fragments of the bacteriophage genomes. As used herein, "a computer-based system" refers to the hardware, software, 20 and data storage media used to analyze the nucleotide sequence information of the present invention. The minimum hardware of the computer-based systems of the present invention comprises a central processing unit (CPU), input device, output device, and data storage medium or media. A skilled artisan will readily recognize that any of the currently available general purpose computer-based system are suitable 25 for use in the present invention, as well as a variety of different specialized or dedicated computer-based systems. As stated above, the computer-based systems of the present invention comprise data storage media having stored therein a nucleotide sequence of the present invention and the necessary hardware and software for supporting and 30 implementing a search and/or analysis program. As used herein, "data storage media" refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention. 35 As used herein, "search program" refers to one or more programs whichiare implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means.
WO 00/32825 PCT/IB99/02040 74 Search means are used to identify fragments or regions of the present gnomic sequences which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based 5 systems of the present invention. Examples of such software includes, but is not limited to, MacPattern (EMBL), BLASTN and BLASTX (NCBIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches and/or sequence analyses can be adapted for use in the present computer-based systems. 10 As used herein in connection with sequence searches and analyses, a "target sequence" can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. Also, the target sequence length is preferably selected to include 15 sequence corresponding to a biologically relevant portion of an encoded product, for example a region which is expected to be conserved across a range of source organisms. Preferably the sequence length of a target polypeptide sequence is from 5 100 amino acids, more preferably 7-50 or 7-100 amino acids, and still more preferably 10-80 or 10-100 amino acids. Preferably the sequence length of a target 20 polynucleotide sequence is from 15-300 nucleotide residues, more preferably from 21 240 or 21-300, and still more preferably 30-150 or 30-300 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length. Likewise, it may be desirable to search and/or analyze longer 25 sequences. As used herein, "a target structural motif," or "target motif," refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein 30 target motifs include, but are not limited to, enzymatic active sites and signal sequences. Nucleic acid target motifs include, but are not limited to promoter sequences, hairpin structures and inducible expression elements (protein binding sequences). A variety of structural formats for the input and output devices can be used to 35 input and output the information in the computer-based systems of the presenf invention. A preferred format for an output device ranks fragments of the bacteriophage or bacterial sequences possessing varying degrees of homology to the WO 00/32825 PCT/IB99/02040 75 target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences which contain various amounts of the target sequence or target motif and identifies the degree of homology contained in the identified fragment. A variety of comparing methods and/or devices and/or formats can be used to 5 compare a target sequence or target motif with the sequence stored in data storage media to identify sequence fragments of the bacteriophage or bacterium in question. One skilled in the art can readily recognize that any one of the publicly available homology search programs can be used as the search program for the computer-based systems of the present invention. Of course, suitable proprietary systems that may be 10 known to those of skill, or later developed, also may be employed in this regard. Figure 6 provides a block diagram of a computer system illustrative of embodiments of this aspect of present invention. The computer system 102 includes a processor 106 connected to a bus 104. Also connected to the bus 104 are a main memory 108 (preferably implemented as random access memory, RAM) and a variety 15 of secondary storage devices 110, such as a hard drive 112 and a removable medium storage device 114. The removable medium storage device 114 may represent, for example, a floppy disk drive, a CD-ROM drive, a magnetic tape drive, etc. A removable storage medium 116 (such as a floppy disk, a compact disk, a magnetic tape, etc.) containing control logic and/or data recorded therein may be inserted into 20 the removable medium storage device 114. The computer system 102 includes appropriate software for reading the control logic and/or the data from the removable medium storage device 114, once it is inserted into the removable medium storage device 114. A nucleotide sequence of the present invention may be stored in a well-known 25 manner in the main memory 108, any of the secondary storage devices 110, and/or a removable storage medium 116. During execution, software for accessing and processing the sequence (such as search tools, comparing tools, etc.) reside in main memory 108, in accordance with the requirements and operating parameters of the operating system, the hardware system and the software program or programs. 30 The data storage medium in which the sequence is embodied and the central processor need not be part of a single stand-alone computer, but may be separated so long as data transfer can occur. For example, the processor or processors being utilized for a search or analysis can be part of one general purpose computer, and the data storage medium can be part of a second general purpose computer connected to a 35 network, or the data storage medium can be part of a network server. As anotTier example the data storage medium can be part of a computer system or network accessible over telephone lines or other remote connection method.
WO 00/32825 PCT/IB99/02040 76 EXAMPLES Example 1. Growth of Staph A bacteriophage 77 and purification of genomic DNA. 5 The Staphylococcus aureus propagating strain (PS 77; ATCC #27699) was used as a host to propagate its respective phage 77 (ATCC # 27699-B 1). Two rounds of plaque purification of phage 77 were performed on soft agar essentially as described in Sambrook et al (1989). Briefly, the PS 77 strain was grown overnight at 37*C in Nutrient broth [NB: 0.3% Bacto beef extract, 0.5% Bacto peptone (Difco 10 Laboratories) and 0.5% NaCl (w/v)].The culture was then diluted 20x in NB and incubated at 37*C until the OD, 0 = .2 (early log phase) with constant agitation. In order to obtain single plaques, phage 77 was subjected to 10-fold serial dilutions using phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCl and 0.1% Gelatin (w/v)) and 10 pl of each dilution was used to infect 0.5 ml of the cell suspension in the presence 15 of 400 pg/ml CaCl 2 . After incubation of 15 min at room temperature (RT), 2 ml of melted soft agar kept at 45 0 C (NB supplemented with 0.6% agar) was added to the mixture and poured onto the surface of 100 mm nutrient agar plates (0.3% Bacto Beef extract, 0.5% Bacto peptone, 0.5% NaCl and 1.5% Bacto agar (w/v)). After overnight incubation at 30"C, a single plaque was isolated, resuspended in 1 ml of phage buffer 20 by end over end rotation for 2 hrs at 20*C, and the phage suspension was diluted and used for a second infection as described above. After overnight incubation at 30*C, a single plaque was isolated and used as a stock. The propagation procedure for bacteriophage 77 was modified from the agar layer method of Swanstorm and Adams (1951). Briefly, the PS 77 strain was grown to 25 stationary phase overnight at 37"C in Nutrient broth. The culture was then diluted twenty-fold in NB and incubated at 37*C until the OD, 4 = .2. The suspension (15x10 7 Bacteria) was then mixed with 15x 10 5 plaque forming units (pfu) to give a ratio of 100-bacteria/phage particle in the presence of 400 pig/ml of CaCl 2 . After incubation for 15 min at 20 0 C, 7.5 ml of melted soft agar (NB plus 0.6% agar) were added to the 30 mixture and poured onto the surface of 150 mm nutrient agar plates and incubated 16 hrs at 30 0 C. To collect the phage plate lysate, 20 ml of NB were added to each plate and the soft agar layer was collected by scrapping off with a clean microscope slide followed by shaking of the agar suspension for 5 min to break up the agar. The mixture was then centrifuged for 10 min at 4,000 RPM (2,830xg) in a JA-10 rotor-- 35 (Beckman) and the supernatant fluid (lysate) was collected and subjected to~a treatment with 10 tg /ml of DNase I and RNase A for 30 min at 37*C. To precipitate the phage particles, the phage suspension was adjusted to 10% (w/v) PEG 8000 and WO 00/32825 PCT/IB99/02040 77 0.5 M of NaCl followed by incubation at 4*C for 16 hrs. The phage was recovered by centrifugation at 4,000 rpm (3,500xg) for 20 min at 4*C on a GS-6R table top centrifuge (Beckman). The pellet was resuspended with 2 ml of phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCl and 0.1% Gelatin). The phage suspension was 5 extracted with 1 volume of chloroform and further purified by centrifugation on a cesium chloride step gradient as described in Sambrook et al. (1989), using a TLS 55 rotor centrifuged in an Optima TLX ultracentrifuge (Beckman) for 2 h at 28,000 rpm (67,000xg) at 4*C. Banded phage was collected and ultracentrifuged again on an isopycnic cesium chloride gradient (1.45 g/ml) at 40,000 rpm (64,000xg) for 24 h at 10 4*C using a TLV rotor (Beckman). The phage was harvested and dialyzed for 4 h at room temperature against 4 L of dialysis buffer consisting of 10 mM NaCl, 50 mM Tris-HCI [pH 8] and 10 mM MgCl 2 . Phage DNA was prepared from the phage suspension by adding 20 mM EDTA, 50 mg/ml Proteinase K and 0.5% SDS and incubating for 1 h at 65"C, followed by successive extractions with 1 volume of 15 phenol, 1 volume of phenol-chloroform and 1 volume of chloroform. The DNA was then dialyzed overnight at 4*C against 4 L of TE (10 mM Tris pH 8.0, 1mM EDTA). Example 2. DNA sequencing of Bacteriophage 77 genome Four micrograms of phage 77 DNA was diluted in 200 pl of TE (10 mM Tris, 20 [pH 8.0], 1 mM EDTA) in a 1.5 ml eppendorf tube and sonication was performed (550 Sonic DismembratorTM, Fisher Scientific). Samples were sonicated under an amplitude of 3 p~m with bursts of 5 s spaced by 15 s cooling in ice/water for 3 to 4 cycles. The sonicated DNA was then size fractionated by electrophoresis on 1% agarose gels utilizing TAE (1 x TAE is: 40 mM Tris-acetate, 1 mM EDTA [pH 8.0]) 25 as the running buffer. Fractions ranging from 1 to 2 kbp were excised from the agarose gel and purified using a commercial DNA extraction system according to the instructions of the manufacturer (Qiagen), with a final elution of 50 pl of 1 mM Tris (pH 8.5). The ends of the sonicated DNA fragments were repaired with a combination of 30 T4 DNA polymerase and the Klenow fragment of E. coli DNA polymerase I, as follows. Reactions were performed in a reaction mixture (final volume, 100 pl) containing sonicated phage DNA, 10 mM Tris-HCl [pH 8.0], 50 mM NaCl, 10 mM MgCl 2 , 1 mM DTT, 50 pg/ml BSA, 100 pM of each dNTP and 15 units of T4 DNA polymerase (New England Biolabs) for 20 min at 12"C followed by addition of 12.5 35 units of Klenow large fragment (New England Biolabs) for 15 min at room temperature. The reaction was stopped by two phenol/chloroform extractions and the WO 00/32825 PCT/IB99/02040 78 DNA was precipitated with ethanol and the final DNA pellet was resuspended in 20 pl of H 2 0. Blunt-ended DNA fragments were cloned by ligation directly into the Hinc II site of pKSII+ vector (New England Biolabs) dephosphorylated by treatment with calf 5 intestinal alkaline phosphatase (New England Biolabs)-treated pKS II+ vector (Stratagene). A typical ligation reaction contained 100 ng of vector DNA, 2 to 5 p1 of repaired sonicated phage DNA (50-100 ng) in a final volume of 20 pl containing 800 units of T4 DNA ligase (New England Biolabs) and was incubated overnight at 16"C. Transformation and selection of bacterial clones containing recombinant plasmids was 10 performed in E. coli DH10p according to standard procedures (Sambrook et al., 1989). Recombinant clones were picked from agar plates into 96-well plates containing 100 pl LB and 100 pig/ml ampicillin and incubated at 37"C. The presence of phage DNA insert was confirmed by PCR amplification using T3 and T7 primers 15 flanking the Hinc II cloning site of the pKS II+ vector. PCR amplification of foreign insert was performed in a 15 pl reaction volume containing 10 mM Tris (pH 8.3), 50 mM KC1, 1.5 mM MgCl 2 , 0.02% gelatin, 1 pM primer, 187.5 pM each dNTP, and 0.75 units Taq polymerase (BRL). The thermocycling parameters were as follows: 2 min initial denaturation at 94*C for 2 min, followed by 20 cycles of 30 sec 20 denaturation at 94*C, 30 sec annealing at 57*C, and 2 min extension at 72*C, followed by a single extension step at 72*C for 10 min. Clones with insert sizes of 1 to 2 kbp were selected and plasmid DNA was prepared from the selected clones using QIAprep T M spin miniprep kit (Qiagen). The nucleotide sequence of the extremities of each recombinant clone was 25 determined using an ABI 377-36 automated sequencer with two types of chemistry: ABI prism Big Dye T M primer or ABI prism Big Dye T M terminator cycle sequencing ready reaction kit (Applied Biosystems). To ensure co-linearity of the sequence data and the genome, all regions of phage genome were sequenced at least once from both directions on two separate clones. In areas that this criteria was not initially met, a 30 sequencing primer was selected and phage DNA was used directly as sequencing template employing ABI prism Big DyeTM terminator cycle sequencing ready reaction kit. Example 3. Bioinformatic management of primary nucleotide sequence from 35 Phage 77. Phage 77 sequence contigs were assembled using SequencherTM 3.1 software (GeneCodes). To close contig gaps, sequencing primers were selected near the edge of WO 00/32825 PCT/IB99/02040 79 the contigs. Phage DNA was used directly as sequencing template employing ABI prism BIG DYETM terminator cycle sequencing ready reaction kit. The complete sequence of bacteriophage 77 is shown in Table 2. A software program was developed and used on the assembled sequence of 5 bacteriophage 77 to identify all putative ORFs larger than 33 codons. Other ORF identification software can also be utilized, preferably programs which allow alternative start codons. The software scans the primary nucleotide sequence starting at nucleotide #1 for an appropriate start codon. Three possible selections can be made for defining the nature of the start codon; I) selection of ATG, II) selection of ATG or 10 GTG, and III) selection of either ATG, GTG, TTG, CTG, ATT, ATC, and ATA. This latter initiation codon set corresponds to the one reported by the NCBI (httip://www.ncbi.nlm.nih. gov/htbin-post/Taxonomv/wprintac?mode=c) for the bacterial genetic code. When an appropriate start codon is encountered, a counting mechanism is 15 employed to count the number of codons (groups of three nucleotides) between this start codon and the next stop codon downstream of it. If a threshold value of 33 is reached, or exceeded, then the sequence encompassed by these two codons (start and stop codons) is defined as an ORF. This procedure is repeated, each time starting at the next nucleotide following the previous stop codon found, in order to identify all 20 the other putative ORFs. The scan is performed on all three reading frames of both DNA strands of the phage sequence. Sequence homology (BLAST) searches for each ORF are then carried out using an implementation of BLAST programs, although any of a variety of different sequence comparison and matching programs can be utilized as known to those 25 skilled in the art. Downloaded public databases used for sequence analysis include: i) non-redundant GenBank (ftp://ncbi.nlm.nih.gov/blast/db/nr.Z), ii) Swissprot (ftp://ncbi.nlm.nih.gov/blast/db/swissprot.Z); iii) vector (ftp://ncbi.nlm.nih.gov/blast/db/vector.Z); iv) pdbaa databases (ftp://ncbi.nlm.nih.gov/blast/db/pdbaa.Z); 30 v) S. aureus NCTC 8325 (ftp://ftp.genome.ou.edu/pub/staph/staph-1k.fa); vi) streptococcus pyogenes (ftp://ftp.genome.ou.edu/pub/strep/strep-1k.fa); vii) Streptococcus pneumoniae (ftp://ftp.tigr.org/pub/data/s_pneumoniae/gsp.contigs. 112197.Z); viii) Mycobacterium tuberculosis CSU#9 35 (ftp://ftp.tigr.org/pub/data/mtuberculosis/TB_091097.Z) and ix) pseudomonas aeruginosa (http://www.izenome.washington.edu/pseudo/data.html).
WO 00/32825 PCT/IB99/02040 80 The results of the homology searches performed on the ORFs is shown in Table 5. Example 4. Subcloning of Bacteriophage 77 ORFs into a Staph A inducible 5 expression system. The shuttle vector pTO02 1, in which the firefly luciferase (lucFF) expression is controlled by the ars (arsenite) promoter/operator (Tauriainen et al., 1997), was modified in the following fashion. Two oligonucleotides corresponding to a short antigenic peptide derived from the heamaglutinin protein of influenza virus (HA 10 epitope tag) were synthesized (Field et al., 1988). The sense strand HA tag sequence (with BamHI, SalI and HindIII cloning sites) is: 5'-gatcccggtcgaccaagcttTACCCATACGACGTCCCAGACTACGCCAGCTGA-3' (where upper case letters denote the nucletotide sequence of the HA tag); the antisense strand HA tag sequence (with a HindIII cloning site) is: 15 5'-agctTCAGCTGGCGTAGTCTGGGACGTCGTATGGGTAaagcttggtcgaccgg-3' (where upper case letters denote the sequence of the HA tag). The two HA tag oligonucleotides were annealed and ligated into pT0021 vector which had been digested with BamHI and HindIII. This manipulation resulted in replacement of the lucFF gene by the HA tag. This modified shuttle vector containing the arsenite 20 inducible promoter, the arsR gene, and HA tag was named pTHA. A diagram outlining our modification of pT0021 to generate pTHA is shown in Fig. 1A. Each ORF, encoded by Bacteriophage 77, larger than 33 amino acids and having a Shine-Dalgarno sequence upstream of the initiation codon was selected for functional analysis for bacterial inhibition. In total, 98 ORFs were selected and 25 screened as detailed below. A list of these is presented in Table 3. Each individual ORF, from initiation codon to last codon (excluding the stop codon), was amplified from phage genomic DNA using the polymerase chain reaction (PCR). For PCR amplification of ORFs, each sense strand primer targets the initiation codon and is preceded by a BamHI restriction site ('cggatcc 3 ) and each antisense oligonucleotide 30 targets the pentultimate codon (the one before the stop codon) of the ORF and is preceded by a Sal I restriction site ( 5 gcgtcgaccg 3 '). The PCR product of each ORF was gel purified and digested with BamHI and SalI. The digested PCR product was then gel purified using the Qiagen kit as described, ligated into BamHI and SalI digested pTHA vector, and used to transform E. coli bacterial strain DH10p(as described - 35 above). As a result of this manipulation, the HA tag is set inframe with the ORF and is positioned at the carboxy terminus of each ORF (pTHA/ORF clones). Recombinant pTHA/ORF clones were picked and their insert sizes were confirmed by PCR analysis WO 00/32825 PCT/IB99/02040 81 using primers flanking the cloning site. The names and sequences of the primers that were used for the PCR amplification were: HAF:
'TATTATCCAAAACTTGAACA
3 '; HAR: "CGGTGGTATATCCAGTGATT". The sequence integrity of cloned ORFs was verified directly by DNA sequencing using 5 primers HAF and HAR. In cases where verification of ORF sequence could not be achieved by one pass with the sequencing primers, additional internal primers were selected and used for sequencing. Staphylococcus aureus strain RN4220 (Kreiswirth et al., 1983) was used as a recipient for the expression of recombinant plasmids. Electoporation was performed 10 essentially as previously described (Schenk and Laddaga, 1992). Selection of recombinant clones was performed on Luria-Broth agar (LB-agar) plates containing 30 pg/ml of kanamycin. For each ORF introduced in the pTHA plasmid, 3 independent transformants were isolated and used to individually inoculate cultures in 5 ml of TSB containing 15 30pg/ml kanamycin, followed by growth to saturation (16 hrs at 30"C). An aliquot of this stationary phase culture was used to generate a frozen glycerol stock of the transformant ( stored at - 80'C). The remaining culture was used for plasmid DNA extraction. Bacterial cells were harvested by centrifugation at 3000 x g at 22*C for 5 min. The pellet was resuspended in 200 pd 25% sucrose containing 25U/ml of 20 lysostaphin and incubated for 15 min at 37*C. Then, 400p1l of alkaline SDS solution (3% SDS, 0.2N NaOH) were added, well mixed and incubated for 7 min at room temperature. After the alkaline SDS treatment, 300pl of ice-cold 3M sodium acetate pH 4.8 were added, and the mix is immediately spun at 13000g for 15 min at room temperature. The supernatant was transferred to a new 1.5 ml conical centrifuge tube 25 and 650p of isopropanol (stored at room temperature) were added. The mix was then centrifuged at 13,000 x g for 5 min. The supernatant fluid was discarded, the pellet washed with 70% ethanol, and resuspended in 320 pl sterile distilled water. The presence of individual phage 77 ORF DNA inserts in the plasmid was verified by PCR amplification using 1.5 1 d transformant miniprep DNA in a PCR 30 with primers flanking the cloning site of ORF in pTHA vector (HAF and HAR). The composition of the PCR reaction and the cycling parameters are identical to those employed for library screening described above. Example 5. Functional assay for bacterial inhibitory activity of bacteriophage 77 35 ORFs. The anti-microbial activity of individual phage 77 ORFs was monitored by two growth inhibitory assays, one on solid agar medium, the other in liquid medium.
WO 00/32825 PCT/IB99/02040 82 In general, Staphylococcus bacteria transformed with expression plasmids containing individual ORFs were grown in normal TSA medium and stored in 19% glycerol. At pre-determined times, arsenite was added to the culture to induce transcription of the phage 77 ORFs cloned immediately downstream from an arsenite-inducible promoter 5 in the pTHA expression plasmid. The effect of ORF induction on bacterial growth characteristics was then monitored and quantitated. The growth inhibition assay on solid medium was performed by streaking pTHA/ORF containing S. aureus transformant onto LB-Kn and TSA-Kn plates containing increasing concentrations of sodium arsenite (0; 2.5; 5; 10 and 7.5 [tM). Arsenite is used to induce the expression of cloned DNA in pTHA vector. In parallel, 3 tl of 1/10 and 1/100 dilutions of the frozen cultures of the pTHA/ORF transformants were spotted as single drops onto LB-Kn and TSA-Kn plates containing increasing concentration of sodium arsenite (0; 2.5; 5; and 7.5 pM). The plates were then incubated 16 hrs at 37*C, and the effect of arsenite-induced ORF 15 expression on bacterial growth was monitored and quantitated by comparing the extent to that seen in control plates. As positive controls for growth inhibition,the holin/lysin genes of the Sthaphylococcus aureus phage Twort (Loessner et al., 1998) was subcloned into the pTHA ars inducible vector and used. For the growth inhibition assay in liquid medium, stationary phase cultures 20 were prepared by inoculating 2.5ml TSB-Kn with frozen S. aureus RN4220 transformants containing phage 77 ORFs cloned in pTHA vector followed by incubation for 16 hrs at 37"C. These cultures were then diluted 1/100 in the same medium, and the bacteria were allowed to grow for 2 hrs at 37 0 C to reach early log phase. 150 pd of such culture were then mixed with 2.35 ml TSB-Kn medium with or 25 without arsenite (the final concentration of arsenite in the medium was 0 or 5 iM arsenite). After 3.5 hrs incubation at 37*C with shaking at 250 rpm, 100 pl of bacterial culture was removed from each tube for OD, measurement. Serial ten-fold dilutions of the culture in buffered saline solution (0.85% NaCl) were then spotted onto TSB-Kn plates. The plates were incubated at 37"C 16 hrs and the number of 30 surviving colonies counted the following day. The growth inhibitory property of individual ORFs was then quantitated by comparing CFU numbers under normal or arsenite-induction conditions. A schematic flow of the inhibition analysis is shown in Fig. 3 (also applicable to inhibition analysis for the other phage and bacteria pointed out herein). Inhibition results are shown in Figures 4A-C. 35 Example 6: Itentification of Cecropin Sipnature Motif in Staphvlococcus aureus Bacteriophage 3A ORF WO 00/32825 PCT/IB99/02040 83 The genome for S. aureus bacteriophage 3A was determined and the sequence was analyzed essentially as described for bacteriophage 77 in the examples above. Upon blast analysis of the identified open reading frames of phage 3A, the presence of an amino acid sequence corresponding to a cecropin signature motif was observed. 5 This motif (WDGHKTLEK) is located at position aa 481-489. Cecropins were originally identified in proteins from the cecropia moth and are recognized as potent antibacterial proteins that constitute an important part of the cell-free immunity of insects. Cecropins are small proteins (31-39 amino acid residues) that are active against both Gram-positive and Gram-negative bacteria by disrupting the bacterial 10 membranes. Although the mechanisms by which the cecropons cause cell death are not fully understood, it is generally thought to involve channel formation and membrane destabilization. The identification of a motif corresponding to a known inhibitor suggests that the product of ORFOO2 is also an inhibitory compound. Such inhibitory activity can 15 be confirmed as described herein or by other methods known in the art. Confirmation of the inhibitory activity would indicate that the ORF product could serve as the basis for construction of mimetic compounds and other inhibitors directed to the target of the ORF002 product. Boman & Hultmark, 1987, Ann. Rev. Microbiol. 41:103-126. 20 Boman, 1991, Cell 65:205-207. Boman et al., 1991, Eur. J. Bioichem. 201:23-3 1. Wang et al., J. Biol. Chem. 273:27438-27448. Example 7. Growth of Staphylococcus aureus bacteriophage 44AHJD: 25 Staphylococcus aureus propagating strain (PS 44A) (Felix d'Herelle Reference Centre #HER 1101) was used as a host to propagate its respective phage 44AHJD (Felix d'Herelle Reference Centre #HER 101). Two rounds of plaque purification of phage 44AHJD were performed on soft agar essentially as described in Sambrook et al. (1989). Briefly, the Staphylococcus aureus PS strain was grown overnight at 37"C 30 in Nutrient Broth [NB: 3 g Bacto Beef Extract, 5 g Bactopeptone per liter, (Difco Laboratories # 0003-17-8), supplemented with 0.5% NaCl]. The culture was then diluted 20 fold in NB and incubated at 37*C until an OD, 0 of 0.2. In order to obtain single plaques, phage 44AHJD was subjected to 10-fold serial dilutions using the phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCl and 0.1% Gelatin) andu10 pl 35 were used to infect 0.5 ml of the cell suspension in the presence of 400 pg/ml of WO 00/32825 PCT/IB99/02040 84 CaCl 2 . After incubation of 15 min at room temperature, 2 ml of melted soft agar (NB supplemented with 0.6% of agar) were added to the mixture and poured onto the surface of 100 mm nutrient agar plates (3 g Bacto Beef extract, 5 g Bactopeptone, 0.5% NaCl and 15 g of Bacto agar per liter (Difco Laboratories # 0001-17-0). After 5 overnight incubation at 37"C, a single plaque was isolated, resuspended in 1ml of phage buffer by end over end rotation for 2 h at room temperature and the phage suspension was diluted and used for a second infection as described above. After overnight incubation at 37"C, a single plaque was isolated and used as a stock. Large scale purification of bacteriophage and preparation of phage DNA was 10 as follows. The propagation method was carried out by using the agar layer method described by Swanstrm and Adams (1951). Briefly, the PS 44A strain was grown to stationary phase overnight at 37*C in Nutrient Broth. The culture was then diluted 20x in NB and incubated at 37*C until the A, 4 1= 0.2. The suspension (15x10 7 Bacteria) 15 was then mixed with 15x10 5 phage particles to give a ratio of 100-bacteria/phage particle in the presence of 400 ptg/ml of CaCl 2 . After incubation of 15 min at room temperature, 7.5 ml of melted soft agar were added to the mixture and poured onto the surface of 150 mm nutrient agar plates and incubated overnight at 37"C. To collect the lysate, 20 ml of NB were added to each plate and the soft agar layer was collected by 20 scrapping off with a clean microscope slide and shaken vigorously for 5 min to break up the agar. The mixture was then centrifuged for 10 min at 4,000 rpm (2,830 xg) using a JA-10 rotor (Beckman) and the supernatant (lysate) is collected and subjected to a treatment with 10 pg/ml of DNase I and RNase A for 30 min at 37"C. To precipitate the phage particles, 10% (w/v) of PEG 8000 and 0.5 M of NaCl were 25 added to the lysate and the mixture was incubated on ice for 16 h. The phage was recovered by centrifugation at 4,000 rpm (3,500 xg) for 20 min at 4"C on a GS-6R table top centrifuge (Beckman). The pellet was resuspended with 2 ml of phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCl and 0.1% Gelatin). The phage suspension was extracted with 1 30 volume of chloroform and further purified by centrifugation on a preformed cesium chloride step gradient as described in Sambrook et al. (1989), using a TLS 55.r6tor and centrifuged in an Optima TLX ultracentrifuge (Beckman) for 2 h at 28,000 rpm (67,000 xg) at 4*C. Banded phage was collected and ultracentrifuged again on an WO 00/32825 PCT/IB99/02040 85 isopycnic cesium chloride gradient (1.45 g/ml) at 40,000 rpm (64,000 x g) for 24 h at 4*C using a TLV rotor (Beckman). The phage was harvested and dialyzed for 4 h at room temperature against 4 L of dialysis buffer consisting of 10 mM NaCl, 50 mM Tris-HC [pH 8] and 10 mM MgCl,. Phage DNA was prepared from the phage 5 suspension by adding 20 mM EDTA, 50 pg/ml Proteinase K and 0.5% SDS and incubating for 1 h at 65*C, followed by successive extractions with 1 volume of phenol, 1 volume of phenol-chloroform and 1 volume of chloroform. The DNA was then dialyzed overnight at 4*C against 4 L of TE (10 mM Tris-HCl [pH 8.0], 1mM EDTA). 10 Example 8. DNA sequencing of the Bacteriophage 44 AHJD Renome. Four mg of phage DNA was diluted in 200 pl of TE pH 8.0 in a 1.5 ml eppendorf tube and sonication was performed (550 Sonic Dismembrator, Fisher Scientific). Samples were sonicated under an amplitude of 3 pm with bursts of 5 s 15 spaced by 15 s cooling in ice/water for 3 to 4 cycles and size fractionated on 1% agarose gels. The sonicated DNA was then size fractionated by gel electrophoresis. Fractions ranging from 1 to 2 kbp were excised from the agarose gel and purified using a coommercial DNA extraction system according to the instructions of the manufacturer (Qiagen) and eluted in 50 pl of lmMTris-HCl [ pH 8.5]. 20 The ends of the sonicated DNA fragments were repaired with a combination of T4 DNA polymearse and the Klenow fragment of E. coli DNA polymerase 1 as follows. Reactions were performed in a final volume of 100 pl containing DNA, 10 mM Tris-HCl pH 8.0, 50 mM NaCl, 10 mM MgCl 2 , 1 ImM DTT, 5 ptg BSA, 100 ptM of each dNTP and 15 units of T4 DNA polymerase (New England Biolabs) for 20 min 25 at 12*C followed by addition of 12.5 units of Klenow fragment (New England Biolabs) for 15 min at room temperature. The reaction was stopped by two phenol/chloroform extractions and the DNA was ethanol precipitated and resuspended in 20 jl of H 2 0. Cloning of the sonicated phage DNA into pKSII vector and transformation: 30 Blunt-ended DNA fragments were cloned by ligation directly into the HinfclI site of the pkSII vector (Stratagene) dephosphorylated with calf intestinal alkaline phosphatase (New England Biolabs). A typical reaction contained 100 ng of vector, 2 WO 00/32825 PCT/IB99/02040 86 to 5 ptl of repaired sonicated phage DNA (50-100 ng) in a final volume of 20 ptl containing 800 units of T4 DNA ligase (New England Biolabs) overnight at 16"C. Transformation and selection of positive clones was performed in the host strain DH10 3 of E. coli using ampicillin as a selective antibiotic as described in Sambrook 5 et al. (1989). Recombinant clones were picked from agar plates into 96-well plates containing 100 ml LB and 100 ig/ml ampicillin and incubated at 37*C. The presence of phage DNA insert was confirmed by PCR amplification using T3 and T7 primers flanking the HincII cloning site of the pKS vector. PCR amplification of the potential 10 foreign inserts was performed in a 15 pl reaction volume containing 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 1.5 mM MgCl 2 , 0.02% gelatin, 1 mM primer, 187.5 IM each dNTP, and 0.75 units Taq polymerase (BRL). The thermocycling parameters were as follows: 2 min initial denaturation at 94*C for 2 min, followed by 20 cycles of 30 sec denaturation at 94*C, 30 sec annealing at 58C, and 2 min extension at 72"C, followed 15 by a single extension step at 72*C for 10 min. Clones with insert sizes of 1 to 2 kbp were selected and plasmid DNA was prepared from the selected clones using the QIAprep T M spin miniprep kit (Qiagen). The nucleotide sequence of the extremities of each recombinant clone was determined using an ABI 377-36 automated sequencer with two types of chemistry: ABI prism 20 BigDye TM primer cycle sequencing (21M13 primer: #403055)(M13REV primer: #403056) or ABI prism BigDye TM terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). To ensure co-linearity of the sequence data and the genome, all regions of the phage genome were sequenced at least once from both directions on two separate clones. In areas that this criteria was not initially met, a 25 sequencing primer was selected and phage DNA was used directly as sequencing template employing ABI prism BigDyeTM terminator cycle sequencing ready reaction kit. ExamDe 9. Bioinformatic management of primary nucleotide sequence. 30 Sequence contigs were assembled using SequencherTM 3.1 software - (GeneCodes). To close contig gaps, sequencing primers were selected near the edge of the contigs. Phage DNA was used directly as sequencing template employing ABI WO 00/32825 PCT/IB99/02040 87 prism BigDye TM terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). The complete sequence of Staphylococcus aureus bacteriophage 44AHJD is shown in Table 16. A software program was used on the assembled sequence of bacteriophage 5 44AHJD to identify all putative ORFs larger than 33 codons. The software scans the primary nucleotide sequence starting at nucleotide #1 for an appropriate start codon. Three possible selections can be made for defining the nature of the start codon; I) selection of ATG, II) selection of ATG or GTG, and III) selection of either ATG, GTG, TTG, CTG, ATT, ATC, and ATA. This latter initiation codon set corresponds 10 to the one reported by the NCBI(http://www.ncbi.nlm.nih.jov/htbin post/Taxonomy/wprintac?mode=c) for the bacterial genetic code. When an appropriate start codon is encountered, a counting mechanism is employed to count the number of codons (groups of three nucleotides) between this start codon and the next stop codon downstream of it. If a threshold value of 33 is reached, or exceeded, 15 then the sequence encompassed by these two codons is defined as an ORF. This procedure is repeated, each time starting at the next nucleotide following the previous stop codon found, in order to identify all the other putative ORFs. The scan is performed on all three reading frames of both DNA strands of the phage sequence. The predicted ORFs for bacteriophage 44AHJD are listed in Tables 17 & 18. 20 Sequence homology searches for each ORF were carried out using an implementation of blast programs. Downloaded public databases used for sequence analysis include: (i) non-redundant GenBank (ftp://ncbi.nlm.nih.gov/blast/db/nr.Z), ii) Swissprot (ftp://ncbi.nlm.nih.gov/blast/db/swissprot.Z); 25 iii) vector (ftp://ncbi.nlm.nih.gov/blast/db/vector.Z); iv) pdbaa databases (ftp://ncbi.nlm.nih.gov/blast/db/pdbaa.Z); v) Staphylococcus aureus NCTC 8325 (ftp://ftp.genome.ou.edu/pub/staph/staph lk.fa); vi)Staphylococcuspyogenes(ftp://ftp.tigr.org/pub/datals-pneumoniae/gsp.contigs. 1121 30 97.Z); vii)PRODOM(ftp://ftp.toulouse.inra.fr/pub/prodom/currentrelease/prodom99J-.forbl ast.gz); viii) DOMO (ftp://ftp.infobiogen.fr/pub/db/domo/); WO 00/32825 PCT/IB99/02040 88 ix) TREMBL (ftp://www.expasy.ch/databases/sptr_nrdb/fasta/) The results of the homology searches performed on the ORFs of bacteriophage 44AHJD are shown in Tables 19 & 20. 5 Example 10. Sub-Cloning of Bacteriophage 44 AHJD ORFs. Expression preferably utilizes a shuttle expression vector which is arranged such that expression of the exogenous bacteriophage 44 AHJD ORF sequence is inducible. For example, the shuttle vector pTO021, in which the firefly luciferase (lucFF) expression is controlled by the ars (arsenite) promoter/operator (Tauriainen et 10 al., 1997), can be modified in the following fashion. Two oligonucleotides corresponding to a short antigenic peptide derived from the heamaglutinin protein of influenza virus (HA epitope tag) were synthesized (Field et al., 1988). The sense strand HA tag sequence (with BamHI, Sal and HindIII cloning sites) is: 5'-gatcccggtcgaccaagcttTACCCATACGACGTCCCAGACTACGCCAGCTGA-3' 15 (where upper case letters denote the nucletotide sequence of the HA tag); the antisense strand HA tag sequence (with a HindIII cloning site) is: 5'-agctTCAGCTGGCGTAGTCTGGGACGTCGTATGGGTAaagcttggtcgaccgg-3' (where upper case letters denote the sequence of the HA tag). The two HA tag oligonucleotides were annealed and ligated into pT0021 vector which had been 20 digested with BamHl and HindIII. This manipulation resulted in replacement of the lucFF gene by the HA tag. This modified shuttle vector containing the arsenite inducible promoter, the arsR gene, and HA tag was named pTHA. A diagram outlining our modification of pT0021 to generate pTHA is shown in Fig. 1A (another userful vector construct is shown in Fig. 1B). 25 Each ORF, encoded by Bacteriophage 44 AHJD, larger than 33 amino acids and having a Shine-Dalgarno sequence upstream of the initiation codon can be selected for functional analysis for bacterial inhibition. Each individual ORF, from initiation codon to last codon (excluding the stop codon), can be amplified from phage genomic DNA using the polymerase chain reaction (PCR). For PCR amplification of 30 ORFs, each sense strand primer targets the initiation codon and is preceded by a BamHI restriction site ('cgeaatcC') and each antisense oligonucleotide targets the pentultimate codon (the one before the stop codon) of the ORF and is preceded by a Sal I restriction site ('gcgtcgaccg"). The PCR product of each ORF can be gel WO 00/32825 PCT/IB99/02040 89 purified and digested with BamHI and SalI. The digested PCR product can then be gel purified using the Qiagen kit as described, ligated into BamHI and SalI digested pTHA vector, and used to transform E. coli bacterial strain DH10p(as described above). As a result of this manipulation, the HA tag is set inframe with the ORF and is 5 positioned at the carboxy terminus of each ORF (pTHA/ORF clones). Recombinant pTHA/ORF clones will be picked and their insert sizes were confirmed by PCR analysis using primers flanking the cloning site. The following primers can be used for PCR amplification: HAF: "TATTATCCAAAACTTGAACA'; HAR: "CGGTGGTATATCCAGTGATT'. The sequence integrity of cloned ORFs can be 10 verified directly by DNA sequencing using primers HAF and HAR. In cases where verification of ORF sequence can not be achieved by one pass with the sequencing primers, additional internal primers will be selected and used for sequencing. Staphylococcus aureus strain RN4220 (Kreiswirth et al., 1983) will be used as a recipient for the expression of recombinant plasmids. Electoporation will be 15 performed essentially as previously described (Schenk and Laddaga, 1992). Selection of recombinant clones will be performed on Luria-Broth agar (LB-agar) plates containing 30 ig/ml of kanamycin. Alternatively, a constitutive promoter can be used to drive expression of the introduced ORF, and compare cell growth to control bacterial cells containing the 20 parental vector lacking any introduced phage ORF. Recombinant plasmids will be introduced into Staphylococcus aureus strain RN4220 (Kreiswirth et al., 1983) using electoporation as previously described (Schenk and Laddaga, 1992). Cloning of ORFs with a Shine-Dalgarno sequence ORFs with a Shine-Dalgamo sequence are selected for functional analysis of 25 bacterial killing. Each ORF, from initiation codon to last codon (excluding the stop codon), can be amplified by PCR from phage genomic DNA. For PCR amplification of ORFs, each sense strand primer starts at the initiation codon and is preceded by a restriction site and each antisense strand starts at the last codon (excluding the stop codon) and is preceded by a different restriction site. The PCR product of each ORF 30 will be gel purified and digested with the restriction enzymes with sites contained on the PCR oligonucleotides. The digested PCR product is then gel purified using4he Qiagen kit, ligated into the modified shuttle vector, and used to transform bacterial strain DH10. Recombinant clones are then picked and their insert sizes confirmed by WO 00/32825 PCT/IB99/02040 90 PCR analysis using primers flanking the cloning site as well as restriction digestion. The sequence fidelity of cloned ORFs can be verified by DNA sequencing using the same primers as used for PCR. In the cases that the verification of ORFs can not be achieved by one path of sequencing using primers flanking the cloning site internal 5 primers can be selected and used for sequencing. Recombinant plasmids can be introduced into Staphylococcus aureus strain RN4220 (Kreiswirth et al., 1983) using electoporation as previously described (Schenk and Laddaga, 1992). Induction of gene expression from the ars promoter. If an inducible promoter is used, e.g., the ars promoter, induction can be 10 assessed, for example, in either of the two methods. 1. Screening on agar plates The functional identification of killer ORFs can be performed by spreading an aliquot of S. aureus transformed cells containing phage 44 AHJD ORFs onto agar plates containing different concentrations of sodium arsenite (0; 2.5; 5; and 7.5 pM). The 15 plates are incubated overnight at 37*C, after which a growth inhibition of the ORF transformants on plates that contain arsenite are compared to plates without arsenite. 2. Ouantification of growth inhibition in liquid medium Cells containing different recombinant plasmids can be grown for overnight at 37*C in LB medium supplemented with the appropriate antibiotic selection. These are 20 then diluted to the mid log phase (OD 540 =.2) with fresh media containing antibiotic and transferred to 96-well microtitration plates (100 pl/well). Inducer is then added at different final concentrations (ranging from 2.5 to 10 tM) and the culture incubated for an additional 2 hrs at 37*C. The effect of expression of the phage 44 AHJD ORFs on bacterial cell growth is then monitored by measuring the OD 40 and comparing the 25 rate of growth to the culture not containing inducer. [As positive controls for growth inhibition, the kilA gene of phage lambda (Reisinger, GR., Rietsch, A., Lubitz, W. and Blasi, U. 1993 Virology #193: 1033-1036), and the holin/lysin genes of the Sthaphylococcus aureus phage Twort (Loessner, MJ., Gaeng, S., Wendlinger, G., Maier, SK. and Scherer, S. 1998. FEMS Microbiology Letters #162:265-274) can be 30 subcloned into the ars inducible vector. An aliquot of the induced and uninduced culture can also be plated out on agar plates containing an appropriate antibiotic selection but lacking inducer. Following incubation overnight at 37*C, the number of WO 00/32825 PCT/IB99/02040 91 colonies is counted. Any ORF showing bacteriostatic activity will show a lower, but detectable, number of colonies on the agar plates when grown in the presence of inducer as compared to when grown in the absence of inducer. Any ORF showing full bacteriocidal activity will show no colonies on the agar plates, when grown in the 5 presence of inducer as compared to when grown in the absence of inducer. REFERENCES Ackermann, H-W. and DuBow, M. S. (1987). Viruses of Prokaryotes. Volumes I and II. CRC Press, Boca Raton, Florida. 10 Tenover, F.C. and McGowan Jr., J.E. (1998). Bacterial Infections of Humans. Epidemiology and Control.(A.S. Evans and P.S. Brachman, eds.) Plenum Medical Book Company, New York, N.Y. pp. 83-93. 15 Rusterholtz, K., and Pohlschroder, M. (1999). Cell 96, 469-470. Gray, B.M. (1998). Bacterial Infections of Humans. Epidemiology and Control.(A.S. Evans and P.S. Brachman, eds.) Plenum Medical Book Company, New York, N.Y. pp. 673 D 711. 20 Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989). Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory, New York. Cold Spring Harbor Laboratory Press. 25 Ausubel, F.M. et al. (1994) Current Protocols in Molecular Biology. John Wiley & Sons, Secaucus, N.J. Rost B,l and Sander C. (1996). Ann. Rev. Biophy. Biomol. Struct. 25, 113-136. 30 Martin, A.C., Lopez, R., Garcia, P. (1998). J Bacteriol 180, 210-217. Steiner, M., Lubitz, W., Blasi, U. (1993). J. Bacteriol. 175, 1038-1042. Durfee, T., Becherer, K., Chen, P.-L., Yeh, S.-H., Yang, Y., Kilburn, A.E., Lee, W.
35 H., and Elledge, S.J. (1993). Genes Dev. 7, 555-569. Qiu, H., Garcia-Barrio, M.T., and Hinnebusch, A.G. (1998). Mol Cell Biol. 18, 2697-2711.
WO 00/32825 PCT/IB99/02040 92 Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura ,Y., and Miki, Y. (1998). Genes, Chromosomes & Cancer 21, 217-222. 5 Endo, T.A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., and Yoshimura, A. (1997). Nature 387, 921-924. 10 Karimova, G., Pidoux, J., Ullmann, A., Ladant, D. (1998) Proc. Natl. Acad. Sci. 95, 5752-5756. Sopta, M., Carthew, R.W., and Greenblatt, J. (1995) J. Biol. Chem. 260, 10353 10369. 15 Qin, J., Fenyo, D., Zhao, Y., Hall, W.W., Chao, D.M., Wilson, C.J., Young, R.A. and Chait, B.T. (1997). Anal. Chem. 69, 3995-4001. Swanstr6m, M. and Adams, M.H. (1951). Proc. Soc. Exptl. Biol. & Med. 78: 372 20 375. Roder, B.L., Wandall, D. A., Frimodt-Moller, N., Epersen, F., Skinhoj, P. and Rosdahl, T. (1999). Arch. Intern. Med. 159: 462-469. 25 Sanabria, T.J., Albert, J.S., Goldberg, R., Pape, L.A. and Cheeseman, S.H. (1990). Arch. Intern. Med. 150: 1305-1309. Frimodt-Moller, N., Epersen, F., Skinhoj, P. and Rosdahl, V.T. (1997). Clin. Microbiol. Infect. 3: 297-305. 30 Harbath, S., Rutschmann, 0., Sudre, P. and Pittet, D. (1998). Arch. Intern. Med. 158: 182-189. Steinberg, J.P., Clark, C.C. and Hackman, B.O. (1996). Clin. Infect. Dis. 23: 255-259. 35 Field, J., Nikawa, J.-I., Broek, D., MacDonald, B., Rodgers, L., Wilson, I.A., Lemer, R.A., and Wigler, M. (1988). Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol. Cell. Biol. 8: 2159-2165. 40 Kreiswirth, BN., Lofdahl, S., Belley, MJ., O'Reilly, M., Shlievert, PM., Bergdoll, MS. and Novicks, RP. (1983) Nature 305: 709-712.
WO 00/32825 PCT/IB99/02040 93 Schenk, S. and Laddaga, RA. (1992) FEMS Microbiology Letters 94: 133-138. Cohen, M.L. (1992) Science 257, 1050-1055. 5 Example 11. Growth of Enterococcus bacteriophage 182 and purification of genomic DNA. The Enterococcus propagating strain (PS) (Enterococcus sp. Group D, Felix d'Herelle Reference Centre #HER 1080) was used as host to propagate its respective 10 phage 182 (Felix d'Herelle Reference Centre #HER 80). Two rounds of plaque purification of phage 182 were performed on soft agar essentially as described in Sambrook et al. (1989). Briefly, the Enterococcus sp. PS strain was grown overnight at 37*C in Tryptic Soy Broth [TSB: 17 g Bacto tryptone, 3 g Bacto soytone, 2.5 g Bacto dextrose, 5 g Sodium chloride, and 2.5 g Dipotassium phosphate per liter 15 (Difco Laboratories (#0370-17-3)]. The culture was then diluted 20 fold in TSB and incubated at 37*C until the OD, 4 = 0.2 (early log phase) with constant agitation. In order to obtain single plaques, phage 182 was subjected to 10 fold serial dilutions using the phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCI and 0.1% Gelatin (w/v)) and 10 1 of each dilution was used to infect 0.5 ml of the bacterial cell 20 suspension. After incubation at 15 min at 37*C, 2 ml of melted soft agar (TSB supplemented with 0.6% agar) was added to the mixture and poured onto the surface of 100 mm Trytic Soy Agar plates [TSA: 15 g Tryptone peptone, 5 g Soytone peptone, 5 g Sodium chloride and 15 g of Agar per liter (Difco Laboratories #0369 17)]. After overnight incubation at 37*C, a single plaque was isolated, resuspended in 25 1 ml of phage buffer by end over end rotation for 2 hrs at room temperature, and the phage suspension was diluted and used for a second infection as described above. After overnight incubation at 37*C, a single plaque was isolated and used as a stock for all subsequent manipulations. The propagation procedure for bacteriophage 182 was modified from the agar 30 layer method of Swanstarm and Adams (1951). Briefly, the Enterococcus sp. PS strain was grown to stationary phase overnight at 37*C in TSB. The culture was then diluted 20 fold in TSB and incubated at 37*C until the A 5 4 = 0.2. The suspension (15x10 7 Bacteria) was then mixed with 15x10 5 plaque forming units (pfu) to give a WO 00/32825 PCT/IB99/02040 94 ratio of 100-bacteria/pfu. After incubation of 15 min at 37*C, 7.5 ml of melted soft agar (TSB plus 0.6% agar) were added to the mixture and poured onto the surface of 150 mm TSA plates and incubated 16 hrs at 37*C. To collect the plate lysate, 20 ml of TSB were added to each plate and the soft agar layer was collected by scrapping off 5 with a clean microscope slide followed by vigorous shaking of the agar suspension for 5 min to break up the agar. The mixture was then centrifuged for 10 min at 4,000 rpm (2,830 xg) using a JA-10 rotor (Beckman) and the supernatant fluid (lysate) is collected and subjected to a treatment with 10 tg /ml of DNase I and RNase A for 30 min at 37*C. To precipitate the phage particles, the phage suspension was adjusted to 10 10% (w/v) of PEG 8000 and 0.5 M of NaCI followed by incubation at 4*C for 16 hrs. The phage was recovered by centrifugation at 4,000 rpm (3,500 xg) for 20 min at 4*C on a GS-6R table top centrifuge (Beckman). The pellet was resuspended with 2 ml of phage buffer (1 mM MgSO 4 , 5 mM MgCl 2 , 80 mM NaCl and 0.1% Gelatin). The phage suspension was extracted with 1 volume of chloroform and further purified by 15 centrifugation on a cesium chloride step gradient as described in Sambrook et al. (1989), using a TLS 55 rotor and centrifuged in an Optima TLX ultracentrifuge (Beckman) for 2 hrs at 28,000 rpm (67,000 xg) at 4*C. Banded phage was collected and ultracentrifuged again on an isopycnic cesium chloride gradient (1.45 g/ml) at 40,000 rpm (64,000 xg) for 24 hrs at 4*C using a TLV rotor (Beckman). The phages 20 were harvested and dialyzed for 4 hrs at room temperature against 4 L of dialysis buffer consisting of 10 mM NaCl, 50 mM Tris-HCl [pH 8] and 10 mM MgCl 2 . Phage DNA was prepared from the phage suspension by adding 20 mM EDTA, 50 g/ml Proteinase K and 0.5% SDS and incubating for 1 hr at 65*C, followed by successive extractions with 1 volume of phenol, 1 volume of phenol-chloroform and 1 volume of 25 chloroform. The DNA was then dialyzed overnight at 4*C against 4 L of TE (10 mM Tris-HCl [pH 8.0], 1mM EDTA). Example 12. DNA sequencing of the Bacteriophage 182 genome. Four micrograms of phage DNA was diluted in 200 pl of TE (10 mM Tris, 30 [pH 8.0], 1 mM EDTA) in a 1.5 ml eppendorf tube and sonication was performed (550 Sonic Dismembrator, Fisher Scientific). Samples were sonicated under an amplitude of 3 ptm with bursts of 5 s spaced by 15 s cooling in ice/water for 3 to 4 WO 00/32825 PCT/IB99/02040 95 cycles. The sonicated DNA was then size fractionated by electrophoresis on 1% agarose gels utilizing TAE (1 x TAE is: 40 mM Tris-acetate, 1 mM EDTA [pH 8.0]) as the running buffer. Fractions ranging from 1 to 2 kbp were excised from the agarose gel and purified using a commercial DNA extraction system according to the 5 instructions of the manufacturer (Qiagen), with a final elution of 50 pl of 1 mM Tris [pH 8.5]. The ends of the sonicated DNA fragments were repaired with a combination of T4 DNA polymerase and the Klenow fragment ofE. coli DNA polymerase I, as follows. Reactions were performed in a reaction mixture (final volume, 100 pl) 10 containing sonicated phage DNA, 10 mM Tris-HCl [pH 8.0], 50 mM NaCl, 10 mM MgC 2 , 1 mM DTT, 50 pig/ml BSA, 100 pM of each dNTP and 15 units of T4 DNA polymerase (New England Biolabs) for 20 min at 12*C followed by addition of 12.5 units of the Klenow large fragment of DNA polymerase I(New England Biolabs) for 15 min at room temperature. The reaction was stopped by two phenol/chloroform 15 extractions and the DNA was precipitated with ethanol and the final DNA pellet resuspended in 20 pl of H 2 0. Blunt-ended DNA fragments were cloned by ligation directly into the Hinc II site of the pKSII+ vector (New England Biolabs) dephosphorylated by treatment with calf intestinal alkaline phosphatase (New England Biolabs). A typical ligation reaction 20 contained 100 ng of vector DNA, 2 to 5 pl of repaired sonicated phage DNA (50-100 ng) in a final volume of 20 p.1 containing 800 units of T4 DNA ligase (New England Biolabs) and was incubated overnight at 16*C. Transformation and selection of bacterial clones containing recombinant plasmids was performed in E. coli DH 1 0P according to standard procedures (Sambrook et al., 1989). 25 Recombinant clones were picked from agar plates into 96-well plates containing 100 pl LB and 100 pg/ml ampicillin and incubated at 37"C. The presence of phage DNA insert was confirmed by PCR amplification using T3 and T7 primers flanking the Hinc II cloning site of the pKS vector. PCR amplification of the potential foreign inserts was performed in a 15 pL reaction volume containing 10 mM Tris (pH 30 8.3), 50 mM KCI, 1.5 mM MgCl 2 , 0.02% gelatin, 1 pM primer, 187.5 p.M each dNTP, and 0.75 units Taq polymerase (BRL). The thermocycling parameters were as follows: 2 min initial denaturation at 94*C for 2 min, followed by 20 cycles of 30 sec WO 00/32825 PCT/IB99/02040 96 denaturation at 94*C, 30 sec annealing at 58'C, and 2 min extension at 72*C, followed by a single extension step at 72'C for 10 min. Clones with insert sizes of 1 to 2 kbp were selected and plasmid DNA was prepared from the selected clones using the QIAprep T M spin miniprep kit (Qiagen). 5 The nucleotide sequence of the extremities of each recombinant clone was determined using an ABI 377-36 automated sequencer with two types of chemistry: ABI prism Big DyeTM primer cycle sequencing (21M13 primer: #403055)(M13REV primer: #403056) or ABI prism Big DyeTM terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). To ensure co-linearity of the sequence data and 10 the genome, all regions of the phage genome were sequenced at least once from both directions on two separate clones. In areas that this criteria was not initially met, a sequencing primer was selected and phage DNA was used directly as sequencing template employing ABI prism BigDyeTM terminator cycle sequencing ready reaction kit. 15 Example 13. Bioinformatic management of primary nucleotide sequence. Sequence contigs were assembled using SequencherTM 3.1 software (GeneCodes). To close contig gaps, sequencing primers were selected near the edge of the contigs. Phage DNA was used directly as sequencing template employing ABI 20 prism BigDyeTM terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). The complete sequence of Enterococcus bacteriophage 182 is shown in Table 21. A software program was used on the assembled sequence of bacteriophage 182 to identify all putative ORFs larger than 33 codons. The software scans the primary 25 nucleotide sequence starting at nucleotide #1 for an appropriate start codon. Three possible selections can be made for defining the nature of the start codon; I) selection of ATG, II) selection of ATG or GTG, and III) selection of either ATG, GTG, TTG, CTG, ATT, ATC, and ATA. This latter initiation codon set corresponds to the one reported by the NCBI(http://www.ncbi.nlm.nih.-Rov/htbin 30 post/Taxonomv/wprintec?mode=c) for the bacterial genetic code. When an appropriate start codon is encountered, a counting mechanism is employed to count the number of codons (groups of three nucleotides) between this start codon and the WO 00/32825 PCT/IB99/02040 97 next stop codon downstream of it. If a threshold value of 33 is reached, or exceeded, then the sequence encompassed by these two codons is defined as an ORF. This procedure is repeated, each time starting at the next nucleotide following the previous stop codon found, in order to identify all the other putative ORFs. The scan is 5 performed on all three reading frames of both DNA strands of the phage sequence. The predicted ORFs for bacteriophage 182 are listed in Tables 22 & 23. Sequence homology searches for each ORF were carried out using an implementation of BLAST programs. Downloaded public databases used for sequence analysis include: 10 (i) non-redundant GenBank (ftp://ncbi.nlm.nih.gov/blast/db/nr.Z), ii) Swissprot (ftp://ncbi.nlm.nih.gov/blast/db/swissprot.Z); iii) vector (ftp://ncbi.nlm.nih.gov/blast/db/vector.Z); iv) pdbaa databases (ftp://ncbi.nlm.nih.gov/blast/db/pdbaa.Z); v) staphylococcus aureus NCTC 8325 (ftp://ftp.genome.ou.edu/pub/staph/staph 15 lk.fa); vi) streptococcus pyrogenes (ftp://ftp.tigr.org/pub/data/s_pneumoniae/gsp.contigs. 112197.Z); vii) PRODOM (ft://ft.toulouse.inra.fr/pub/prodom/current release/prodom99.1.forblast.2z); 20 viii) DOMO (ft://ftp.infobiogen.fr/pub/db/domo/); ix) TREMBL (ftp://www.expasy.ch/databases/sptrnrdb/fasta/) The results of the homology searches performed on the ORFs of bacteriophage 182 are shown in Tables 24 & 26. 25 Example 14. Sub-Cloning of Bacteriophage 182 ORFs. Preparation of the shuttle expression vector Expression preferably utilizes a shuttle expression vector which is arranged such that expression of the exogenous bacteriophage 182 ORF sequence is inducible. For example, the plasmid pND50 replicates in E. coli, E. faecalis, and S. aureus 30 (Yamagishi, J., Kojima, T., Oyamada, Y., Fujimoto, K., Hattori, H., Nakamura, S., and Inoue, M. 1996. Antimocrob. Agents Chemother. 40, 1157-1163). This plasmid can be modified by conventional techniques to insert the inducible arsenite promoter, derived from the shuttle vector pTO02 1, in which the firefly luciferase (lucFF) WO 00/32825 PCT/IB99/02040 98 expression is controlled by the ars promoter/operator from a S. aureus plasmid (Tauriainen, S., Karp, M., Chang, W and Virta, M. (1997). Recombinant luminescent bacteria for measuring bioavailable arsenite and antimonite. Apple. Environ. Microbiol. 63:4456-4461). This modified shuttle vector will contain the ars promoter, arsR gene 5 and a cloning site for introduction of individual phage ORFs downstream from a shine-delgamo sequence. Other inducible regulatory sequences can be utilized instead of the arsenite inducible system. An example is a nisin-inducible system The nisA promoter activity is dependent on the proteins NisR and NisK, which constitute a two-component signal 10 transduction system that responds to the extracellular inducer nisin. The nisin sensitivity and inducer concentration required for maximal induction varies among the strains, but is functional in Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcusfaecalis, and Bacillus subtilis. Significant induction of the nisA promoter (10- to 60-fold induction) can be obtained in all of the 15 species. A vector containing this promoter was published as Eichenbaum Z, Federle MJ, Marra D, de Vos WM, Kuipers OP, Kleerebezem M, and Scott JR (1998) Appl Environ Microbiol 64, 2763-2769. Other vectors, e.g., plasmids, can also be utilized which will allow replication and transciption in Enterococcus. Alternatively, a constitutive promoter can be used (e.g,, the p-lactamase 20 promoter is constitutive in E.faecalis - see ref. 1) to drive expression of the introduced ORF, and compare cell growth to control bacterial cells containing the parental vector lacking any introduced phage ORF. Recombinant plasmids are introduced into E. faecalis strain FA2-2 by electroporation, as previously described (Yamagishi, J., Kojima, T., Oyamada, Y., Fujimoto, K., Hattori, H., Nakamura, S., 25 and Inoue, M. 1996. Antimicrob. Agents Chemother. 40, 1157-1163). Cloning of ORFs with a Shine-Dalgarno sequence ORFs with a Shine-Dalgamo sequence are selected for functional analysis of bacterial killing. Each ORF, from initiation codon to last codon (excluding the stop codon), will be amplified by PCR from phage genomic DNA. For PCR amplification 30 of ORFs, each sense strand primer starts at the initiation codon and is preceded by a restriction site and each antisense strand starts at the last codon (excluding the stop codon) and is preceded by a different restriction site. The PCR product of each ORF will be gel purified and digested with the restriction enzymes with sites contained on WO 00/32825 PCT/IB99/02040 99 the PCR oligonucleotides. The digested PCR product is then gel purified using the Qiagen kit, ligated into the modified shuttle vector, and used to transform bacterial strain DH1Op. Recombinant clones are then picked and their insert sizes confirmed by PCR analysis using primers flanking the cloning site as well as restriction digestion. 5 The sequence fidelity of cloned ORFs will be verified by DNA sequencing using the same primers as used for PCR. In the cases that the verification of ORFs can not be achieved by one path of sequencing using primers flanking the cloning site internal primers will be selected and used for sequencing. Recombinant plasmids will be introduced into E. faecalis strain FA2-2 by electroporation, as previously described 10 (Yamagishi, J., Kojima, T., Oyamada, Y., Fujimoto, K., Hattori, H., Nakamura, S., and Inoue, M. 1996. Antimicrob. Agents Chemother. 40, 1157-1163). Induction of gene expression from the ars promoter. If an inducible promoter is used, e.g., the ars promoter, induction can be assessed, for example, in either of the two methods. 15 1. Screening on agar plates The functional identification of killer ORFs can be performed by spreading an aliquot of E. faecalis transformed cells containing phage 182 ORF onto agar plates containing different concentrations of sodium arsenite (0; 2.5; 5; and 7.5 pM). The plates are incubated overnight at 37*C, after which a growth inhibition of the ORF 20 transformants on plates that contain arsenite are compared to plates without arsenite. 2. Quantification of growth inhibition in liquid medium Cells containing different recombinant plasmids can be grown for overnight at 37*C in LB medium supplemented with the appropriate antibiotic selection. These are then diluted to the mid log phase (OD 540 =.2) with fresh media containing antibiotic 25 and transferred to 96-well microtitration plates (100 pil/well). Inducer is then added at different final concentrations (ranging from 2.5 to 10 pLM) and the culture incubated for an additional 2 h at 37 0 C. The effect of expression of the phage 182 ORFs on bacterial cell growth is then monitored by measuring the ODS 4 0 and comparing the rate of growth to the culture not containing inducer. As positive controls for growth 30 inhibition, the kilA gene of phage lambda (Reisinger, GR., Rietsch, A., Lubitz, W. and Blasi, U. 1993 Virology #193: 1033-1036), and the holin/lysin genes of the Sthaphylococcus aureus phage Twort (Loessner, MJ., Gaeng, S., Wendlinger, G., WO 00/32825 PCT/IB99/02040 100 Maier, SK. and Scherer, S. 1998. FEMS Microbiology Letters #162:265-274) were subcloned into the ars inducible vector. An aliquot of the induced and uninduced culture can also be plated out on agar plates containing an appropriate antibiotic selection but lacking inducer. Following incubation overnight at 37 0 C, the number of 5 colonies is counted. Any ORF showing bacteriostatic activity will show a lower, but detectable, number of colonies on the agar plates when grown in the presence of inducer as compared to when grown in the absence of inducer. Any ORF showing bacteriocidal activity will show no colonies on the agar plates, when grown in the presence of inducer as compared to when grown in the absence of inducer. 10 REFERENCES 1. Cohen, M.L. (1992). Science 257, 1050-1055. 2. Tenover, F.C. and McGowan Jr., J.E. (1998). Bacterial Infections of Humans. Epidemiology and Control.(A.S. Evans and P.S. Brachman, eds.) Plenum Medical 15 Book Company, New York, N.Y. pp. 83-93. 3. Rusterholtz, K., and Pohlschroder, M. (1999). Cell 96, 469-470. 4. Neu, H.C. (1992). Science 257, 1064-1073. 5. Murray, B.E. (1990). Clin. Microbiol. Rev. 3, 46-65. 6. Gray, B.M. (1998). Bacterial Infections of Humans. Epidemiology and 20 Control.(A.S. Evans and P.S. Brachman, eds.) Plenum Medical Book Company, New York, N.Y. pp. 673 - 711. * Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989). Molecular cloning: A laboratory Manual. Cold Spring Harbor Laboratory, New York. Cold Spring Harbor Laboratory Press. 25 7. Ausubel, F.M. et al. (1994) Current Protocols in Molecular Biolo&v. John Wiley & Sons, Secaucus, N.J. 8. Rost B,1 and Sander C. (1996). Ann. Rev. Biophy. Biomol. Struct. 25, 113-136. 9. Garvey, K.J., Saedi, M.S., and Ito, J. (1985). Gene 40, 311-316. 10. Pickett, G.G. and Peabody, D.S. (1993). Nucl. Acids Res. 21, 4621-4626. 30 11. Gutidrrez, J., Vinos, J., Prieto, I., Mendez, E., Hermoso, J., and Salas, M. (1986). Virology 155, 474-483. 12. Yoshikawa, H., Garvey, K.J., and Ito, J. (1985). Gene 37, 125-130. 13. Martin, A.C., Lopez, R., Garcia, P. (1998). J Bacteriol 180, 210-217.
WO 00/32825 PCT/IB99/02040 101 14. Steiner, M., Lubitz, W., Blasi, U. (1993). J. Bacteriol. 175, 1038-1042. * Durfee, T., Becherer, K., Chen, P.-L., Yeh, S.-H., Yang, Y., Kilburn, A.E., Lee, W.-H., and Elledge, S.J. (1993). Genes Dev. 7, 555-569. * Qiu, H., Garcia-Barrio, M.T., and Hinnebusch, A.G. (1998). Mol Cell Biol. 18, 5 2697-2711. * Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura ,Y., and Miki, Y. (1998). Genes, Chromosomes & Cancer 21, 217-222. * Endo, T.A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor 10 N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., and Yoshimura, A. (1997). Nature 387, 921-924. * Karimova, G., Pidoux, J., Ullmann, A., Ladant, D. (1998) Proc. Natl. Acad. Sci. 95, 5752-5756. * Sopta, M., Carthew, R.W., and Greenblatt, J. (1995) J. Biol. Chem. 260, 10353 15 10369. * Qin, J., Fenyo, D., Zhao, Y., Hall, W.W., Chao, D.M., Wilson, C.J., Young, R.A. and Chait, B.T. (1997). Anal. Chem. 69, 3995-4001. * Swanstrum, M. and Adams, M.H. (1951). Proc. Soc. Exptl. Biol. Med. 78, 372 375. 20 Example 15. Growth of Streptococcus bacteriophage Dp-1 and purification of genomic DNA. The Streptococcus pneumoniae R6 propagating strain (PS) (Tomasz, 1966) was used as host to propagate its respective phage Dp-1 (McDonnell et al., 25 1975). (Alternatively, Streptococcus (Diplococcus) pneumoniae R36A could be used. Strain R36A is available from ATCC as #11733 or 27336. Streptococcus pneumoniae is also available from Felix d'Herelle Reference Center in Quebec, Canada as catalog number HER 1054. Other S. pneumoniae strains are also available from ATCC.) Two rounds of plaque purification of phage Dp-1 were performed on soft agar 30 essentially as described in Sambrook et al. (1989). Briefly, the Streptococcus R6 PS strain was grown overnight at 37*C in K-Cat media [K-Cat: 10 g Bacto casitone, 5 g Bacto tryptone, 1 g Yeast extract, 5g Potassium chloride, 0.2% Glucose, 30mM Potassium phosphate buffer [pH 8] and 250,000 Units Catalase per liter (Boehringer Mannheim #10683600). The culture was then diluted 20 fold in K-CAT and WO 00/32825 PCT/IB99/02040 102 incubated at 37"C until the OD 540 = 0.2 (early log phase) with constant agitation. In order to obtain single plaques, Dp- 1 phage was subjected to 10-fold serial dilutions using the phage buffer (100 mM Tris-HCI [pH 7.5], 100 mM NaCl and 10 mM MgCl 2 )and 10 pl of each dilution was used to infect 0.5 ml of the cell suspension. 5 After incubation of 15 min at 37*C, 2 ml of melted soft agar (K-CAT supplemented with 0.8% of agar) were added to the mixture and poured onto the surface of 100 mm K-CAT agar plates [K-CAT supplemented with 1.2 % of agar]. After solidification of the soft agar layer, an additional 5 ml of melted soft agar was added to visualize distinct plaques (Ronda et al., 1978). After overnight incubation at 37"C, a single 10 plaque was isolated, resuspended in 1 ml of phage buffer by end over end rotation for 2 hrs at room temperature, and the phage suspension was diluted and used for a second infection as described above. After overnight incubation at 37 0 C, a single plaque was isolated and used as a stock for all subsequent manipulations. The propagation procedure for bacteriophage Dp--1 was modified from the 15 agar layer method of Swanst6rm and Adams (1951). Briefly, the R6 strain of Streptococcus pneumoniae was grown to stationary phase overnight at 37"C in K CAT. The culture was then diluted 20 fold in K-CAT and incubated at 37*C until the
OD
540 = 0.2. The suspension (15x10 7 Bacteria) was then mixed with 15x10 5 plaque forming units (pfu) to give a ratio of 100-bacteria/pfu. After incubation of 15 min at 20 37*C, 7.5 ml of melted soft agar (K-CAT plus 0.8% agar) were added to the mixture and poured onto the surface of 150 mm K-CAT agar plates and incubated 16 hrs at 37*C. After solidification of the soft agar layer, 7.5 ml of melted soft agar were added to each plate. To collect the plate lysate, 20 ml of K-CAT media were added to each plate and the soft agar layers were collected by scrapping off with a clean microscope 25 slide followed by vigorous shaking of the agar suspension for 5 min to break up the agar. The mixture was then centrifuged for 10 min at 4,000 rpm (2,830 xg) using a JA-10 rotor (Beckman) and the supernatant (lysate) was collected and subjected to a treatment with 10 pg /ml of DNase I and RNase A for 30 min at 37"C. To precipitate the phage particles, the phage suspension was adjusted to 10% (w/v) of PEG 8000 and 30 0.5 M of NaCl followed by incubation at 4*C for 16 hrs. The phage was recovered by centrifugation at 4,000 rpm (3,500 xg) for 20 min at 4 0 C on a GS-6R table top centrifuge (Beckman). The pellet was resuspended with 2 ml of phage buffer (100 mM Tris-HCl [pH 7.5], 100 mM NaCl and 10 mM MgCl 2 ). The phage suspension was extracted with 1 volume of chloroform and further purified by centrifugation on a 35 cesium chloride step gradient as described in Sambrook et al. (1989), using a TLS-5-5 rotor and centrifuged in an Optima TLX ultracentrifuge (Beckman) for 2 hrs at 28,000 rpm (67,000 xg) at 4*C. Banded phage was collected and ultracentrifuged again on an WO 00/32825 PCT/IB99/02040 103 isopycnic cesium chloride gradient (1.45 g/ml) at 40,000 rpm (64,000 xg) for 24 hrs at 4"C using a TLV rotor (Beckman). The phage was harvested and dialyzed for 4 hrs at room temperature against 4 L of dialysis buffer consisting of 10 mM NaCl, 50 mM Tris-HCI [pH 8] and 10 mM MgCl2. Phage DNA was prepared from the phage 5 suspension by adding 20 mM EDTA, 50 pg/ml Proteinase K and 0.5% SDS and incubating for 1 hr at 65*C, followed by successive extractions with 1 volume of phenol, 1 volume of phenol-chloroform and 1 volume of chloroform. The DNA was then dialyzed overnight at 4*C against 4 L of TE (10 mM Tris-HCl [pH 8.0], 1mM EDTA). 10 Example 16. DNA sequencing of the Bacteriophage Dp-1 Renome. Four micrograms of phage DNA was diluted in 200 pl of TE (10 mM Tris, [pH 8.0], 1 mM EDTA) in a 1.5 ml eppendorf tube and sonication was performed (550 Sonic Dismembrator, Fisher Scientific). Samples were sonicated under an 15 amplitude of 3 pm with bursts of 5 sec spaced by 15 sec cooling in ice/water for 3 to 4 cycles. The sonicated DNA was then size fractionated by electrophoresis on 1% agarose gels utilizing TAE (1 x TAE is: 40 mM Tris-acetate, 1 mM EDTA [pH 8.0]) as the running buffer. Fractions ranging from 1 to 2 kbp were excised from the agarose gel and purified using a commercial DNA extraction system according to the 20 instructions of the manufacturer (Qiagen), with a final elution of 50 pl of 1 mM Tris [pH 8.5]. The ends of the sonicated DNA fragments were repaired with a combination of T4 DNA polymerase and the Klenow fragment ofE. coli DNA polymerase I, as follows. Reactions were performed in a reaction mixture (final volume, 100 pl) 25 containing sonicated phage DNA, 10 mM Tris-HCI [pH 8.0], 50 mM NaCl, 10 mM MgCl 2 , 1 mM DTT, 50 pg/ml BSA, 100 pM of each dNTP and 15 units of T4 DNA polymerase (New England Biolabs) for 20 min at 12*C followed by addition of 12.5 units of the Klenow large fragment of DNA polymerase I (New England Biolabs) for 15 min at room temperature. The reaction was stopped by two phenol/chloroform 30 extractions and the DNA was precipitated with ethanol and the final DNA pellet resuspended in 20 pl of H 2 0. Blunt-ended DNA fragments were cloned by ligation directly into the Hinc II site of the pKSII+ vector (New England Biolabs) dephosphorylated by treatment with calf intestinal alkaline phosphatase (New England Biolabs). A typical ligation 35 reaction contained 100 ng of vector DNA, 2 to 5 p1 of repaired sonicated phage DNA (50-100 ng) in a final volume of 20 pl containing 800 units of T4 DNA ligase (New England Biolabs) and was incubated overnight at 16*C. Transformation and selection WO 00/32825 PCT/IB99/02040 104 of bacterial clones containing recombinant plasmids was performed in E. coli DH 10P according to standard procedures (Sambrook et al., 1989). Recombinant clones were picked from agar plates into 96-well plates containing 100 pl LB and 100 pg/ml ampicillin and incubated at 37*C. The presence 5 of phage DNA insert was confirmed by PCR amplification using T3 and T7 primers flanking the Hinc II cloning site of the pKS vector. PCR amplification of the potential foreign inserts was performed in a 15 pl reaction volume containing 10 mM Tris (pH 8.3), 50 mM KCl, 1.5 mM MgCl 2 , 0.02% gelatin, 1 pM primer, 187.5 ptM each dNTP, and 0.75 units Taq polymerase (BRL). The thermocycling parameters were as 10 follows: 2 min initial denaturation at 94'C for 2 min, followed by 20 cycles of 30 sec denaturation at 94*C, 30 sec annealing at 58'C, and 2 min extension at 72*C, followed by a single extension step at 72*C for 10 min. Clones with insert sizes of 1 to 2 kbp were selected and plasmid DNA was prepared from the selected clones using the QIAprep T M spin miniprep kit (Qiagen). 15 The nucleotide sequence of the extremities of each recombinant clone was determined using an ABI 377-36 automated sequencer with two types of chemistry: ABI prism Big Dye TM primer cycle sequencing (21M13 primer: #403055)(M13REV primer: #403056) or ABI prism Big DyeTm terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). To ensure co-linearity of the sequence data and 20 the genome, all regions of the phage genome were sequenced at least once from both directions on two separate clones. In areas that this criteria was not initially met, a sequencing primer was selected and phage DNA was used directly as sequencing template employing ABI prism Big DyeTM terminator cycle sequencing ready reaction kit. 25 Example 17. Bioinformatic management of primary nucleotide sequence. Sequence contigs were assembled using SequencherTM 3.1 software (GeneCodes). To close contig gaps, sequencing primers were selected near the edge of the contigs. Phage DNA was used directly as sequencing template employing ABI 30 prism BigDyeTM terminator cycle sequencing ready reaction kit (Applied Biosystems; #4303152). The complete sequence of Streptococcus bacteriophage Dp-1 is shown in Table 28. A software program was used on the assembled sequence of bacteriophage Dp-l to identify all putative ORFs larger than 33 codons. The software scans the 35 primary nucleotide sequence starting at nucleotide #1 for an appropriate start codoir Three possible selections can be made for defining the nature of the start codon; I) selection of ATG, II) selection of ATG or GTG, and III) selection of either ATG, WO 00/32825 PCT/IB99/02040 105 GTG, TTG, CTG, ATT, ATC, and ATA. This latter initiation codon set corresponds to the one reported by the NCBI(http://www.ncbi.nlm.nih.gov/htbin post/Taxonomy/wprintec?mode=c) for the bacterial genetic code. When an appropriate start codon is encountered, a counting mechanism is employed to count 5 the number of codons (groups of three nucleotides) between this start codon and the next stop codon downstream of it. If a threshold value of 33 is reached, or exceeded, then the sequence encompassed by these two codons is defined as an ORF. This procedure is repeated, each time starting at the next nucleotide following the previous stop codon found, in order to identify all the other putative ORFs. The scan is 10 performed on all three reading frames of both DNA strands of the phage sequence. The predicted ORFs for bacteriophage Dp-1 are listed in Tables 29 and 30, and Fig. 6. Sequence homology searches for each ORF were carried out using an implementation of BLAST programs. Downloaded public databases used for sequence analysis include: 15 (i) non-redundant GenBank (ftp://ncbi.nlm.nih.gov/blast/db/nr.Z), ii) Swissprot (ftp://ncbi.nlm.nih.gov/blast/db/swissprot.Z); iii) vector (ftp://ncbi.nlm.nih.gov/blast/db/vector.Z); iv) pdbaa databases (ftp://ncbi.nlm.nih.gov/blast/db/pdbaa.Z); v) staphylococcus aureus NCTC 8325 20 (ftp://ftp.genome.ou.edu/pub/staph/staph-1k.fa); vi) streptococcus pyogenes (ftp://ftp.tigr.org/pub/data/s_pneumoniae/gsp.contigs. 112197.Z); vii) PRODOM (fip://ftp.toulouse.inra.fr/pub/prodom/current release/prodom99.1.forblast. iz); 25 viii) DOMO (ftp://ftp.infobiogen.fr/pub/db/domo/); ix) TREMBL (ftp://www.expasy.ch/databases/sptr-nrdb/fasta/) The results of the homology searches performed on the ORFs of bacteriophage Dp-1 are shown in Table 31. 30 Example 18. Sub-Cloning of Bacteriophage Dp-1 ORFs. Preparation of the shuttle expression vector Expression preferably utilizes a shuttle expression vector which is arranged such that expression of the exogenous bacteriophage Dp- 1 ORF sequence is inducible. 35 For example, the plasmid pLSE4 replicates in E. coli, and S. pneumoniae (Diazand Garcia, 1990). This plasmid can be modified by conventional techniques to insert the inducible arsenite promoter, derived from the shuttle vector pT002 1, in which the WO 00/32825 PCT/IB99/02040 106 firefly luciferase (lucFF) expression is controlled by the ars promoter/operator from a S. aureus plasmid (Tauriainen, S., Karp, M., Chang, W and Virta, M. (1997). Recombinant luminescent bacteria for measuring bioavailable arsenite and antimonite. Apple. Environ. Microbiol. 63:4456-4461). This modified shuttle vector will contain 5 the ars promoter, arsR gene and a cloning site for introduction of individual phage ORFs downstream from a shine-dalgarno sequence. Other inducible regulatory sequences can be utilized instead of the arsenite inducible system. An example is a nisin-inducible system The nisA promoter activity is dependent on the proteins NisR and NisK, which constitute a two-component signal 10 transduction system that responds to the extracellular inducer nisin. The nisin sensitivity and inducer concentration required for maximal induction varies among the strains, but is functional in Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcusfaecalis, and Bacillus subtilis. Significant induction of the nisA promoter (10- to 60-fold induction) can be obtained in all of the 15 species. A vector containing this promoter was published as Eichenbaum Z, Federle MJ, Marra D, de Vos WM, Kuipers OP, Kleerebezem M, and Scott JR (1998) Appl Environ Microbiol 64, 2763-2769. Other vectors, e.g., plasmids, can also be utilized which will allow replication and transcription in Streptococcus. Alternatively, a constitutive promoter can be used to drive expression 20 of the introduced ORF, and compare cell growth to control bacterial cells containing the parental vector lacking any introduced phage ORF. Recombinant plasmids are introduced into S. pneumoniae R6 as previously described (Diaz and Garcia, 1990) Cloning of ORFs with a Shine-Dalgarno sequence 25 ORFs with a Shine-Dalgarno sequence are selected for functional analysis of bacterial killing. Each ORF, from initiation codon to last codon (excluding the stop codon), will be amplified by PCR from phage genomic DNA. For PCR amplification of ORFs, each sense strand primer starts at the initiation codon and is preceded by a restriction site and each antisense strand starts at the last codon (excluding the stop 30 codon) and is preceded by a different restriction site. The PCR product of each ORF will be gel purified and digested with the restriction enzymes with sites contained on the PCR oligonucleotides. The digested PCR product is then gel purified using the Qiagen kit, ligated into the modified shuttle vector, and used to transform bacterial strain DH10P. Recombinant clones are then picked and their insert sizes confirmed 35 by PCR analysis using primers flanking the cloning site as well as restriction digestion. The sequence fidelity of cloned ORFs will be verified by DNA sequencing using the same primers as used for PCR. In the cases that the verification of ORFs can not be achieved by one path of sequencing using primers flanking the cloning site WO 00/32825 PCT/IB99/02040 107 internal primers will be selected and used for sequencing. Recombinant plasmids will be introduced into S. pneumoniae R6 as previously described (Diaz and Garcia, 1990). Induction of gene expression from the ars promoter. If an inducible promoter is used, e.g., the ars promoter, induction can be 5 assessed, for example, in either of the two methods. 1. Screening on agar plates The functional identification of killer ORFs can be performed by spreading an aliquot of S. pneumoniae transformed cells containing phage Dp-1 ORFs onto agar plates containing different concentrations of sodium arsenite (0; 2.5; 5; and 7.5 pM). 10 The plates are incubated overnight at 37 0 C, after which a growth inhibition of the ORF transformants on plates that contain arsenite are compared to plates without arsenite. 2. Ouantification of growth inhibition in liquid medium Cells containing different recombinant plasmids can be grown for overnight at 15 37*C in LB medium supplemented with the appropriate antibiotic selection. These are then diluted to the mid log phase (OD 5 40 =.2) with fresh media containing antibiotic and transferred to 96-well microtitration plates (100 pil/well). Inducer is then added at different final concentrations (ranging from 2.5 to 10 pLM) and the culture incubated for an additional 2 hrs at 37*C. The effect of expression of the phage Dp-1 ORFs on 20 bacterial cell growth is then monitored by measuring the OD, 40 and comparing the rate of growth to the culture not containing inducer. [As positive controls for growth inhibition, the kilA gene of phage lambda (Reisinger, GR., Rietsch, A., Lubitz, W. and Blasi, U. 1993 Virology #193: 1033-1036), and the holin/lysin genes of the Sthaphylococcus aureus phage Twort (Loessner, MJ., Gaeng, S., Wendlinger, G., 25 Maier, SK. and Scherer, S. 1998. FEMS Microbiology Letters #162:265-274) can be subcloned into the ars inducible vector. An aliquot of the induced and uninduced culture can also be plated out on agar plates containing an appropriate antibiotic selection but lacking inducer. Following incubation overnight at 37*C, the number of colonies is counted. Any ORF showing bacteriostatic activity will show a lower, but 30 detectable, number of colonies on the agar plates when grown in the presence of inducer as compared to when grown in the absence of inducer. Any ORF showing full bacteriocidal activity will show no colonies on the agar plates, when grown in the presence of inducer as compared to when grown in the absence of inducer. 35 REFERENCES 15. Cohen, M.L. (1992) Science 257, 1050-1055.
WO 00/32825 PCT/IB99/02040 108 16. Tenover, F.C. and McGowan Jr., J.E. (1998) Bacterial Infections of Humans. Epidemiology and Control.(A.S. Evans and P.S. Brachman, eds.) Plenum Medical Book Company, New York, N.Y. pp. 83-93. 5 17. Rusterholtz, K., and Pohlschroder, M. (1999) Cell 96, 469-470. 18. Klugman, K.P. (1990) Clin. Microbiol. Rev. 3, 171-196. 19. Fenoll, A., Martin Bourgon, C., Munoz, R., Vicioso, D., Casal, J. (1991) Rev. 10 Infect. Disease 13, 56-60. 20. Jorgensen, J.H., Doern, G. V., Maher, L. A., Howell, A. W., Redding, J. S. (1990) Antimicrob. Agents Chemother. 34, 2075-2080. 15 21. Neu, H.C. (1992) Science 257, 1064-1073. 0 Hsueh, P. R., Wu, J. J., Hsiue, T. R. (1996) J Formos Med Assoc5, 364-371. * Garcia, P., Martin, A.C., and Lopez, R. (1997) Microbial Drug Res. 3, 165-176. 20 * Martin, A.C., Lopez, R., and Garcia, P. (1996) J. Virol. 70, 3678-3687. 0 Sheehan, M.M., Garcia, J.L., Lopez, R., and Garcia, P. (1997) Mol. Microbiol. 25, 717-725. 25 * Kodaira, M., Biswas, S.B., and Kornberg, A. (1983) Mol. Gen. Genet. 192, 80-96. * Maki, S. and Kornberg, A. (1988) J. Biol. Chem.263, 6547-6554. 30 * Tsuchihashi Z, Kornberg A. (1990) Proc. Natl. Acad. Sci. USA. 87, 2516-2520. 0 Lee, S.H. and Walker, J.R. (1987) Proc Natl Acad Sci USA 84, 2713-2717. 0 Smidt, C.R., Steinberg, F.M., Rucker, R. (1991) Proc Soc Exp Biol Med 197, 19 35 26. * Frank, D.W, (1997) Mol Microbiol. 26, 621-629. * Nardese, V., Gutlich, M., Brambilla, A., Carbone, M.L.(1996) Biochem Biophys Res Commun 218, 273-279. 40 * Mancini, R., Saracino, F., Buscemi, G., Fischer, M., Schramek, N., Bracher, A., Bacher, A., Gutlich, M., Carbone, M.L. (1999) Biochem Biophys Res Commun 255,521-527. 45 9 Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989) Molecular cloning -A laboratory Manual. Cold Spring Harbor Laboratory, New York. Cold' Spring Harbor Laboratory Press.
WO 00/32825 PCT/IB99/02040 109 22. Ausubel, F.M. et al. (1994) Current Protocols in Molecular BioloUv. John Wiley & Sons, Secaucus, N.J. 23. Rost B,1 and Sander C. (1996) Ann. Rev. Biophy. Biomol. Struct. 25, 113-136. 5 24. Garvey, K.J., Saedi, M.S., and Ito, J. (1985) Gene 40, 311-316. 25. Pickett, G.G. and Peabody, D.S. (1993) Nucl. Acids Res. 21, 4621-4626. 10 26. Guti6rrez, J., Vinos, J., Prieto, I., Mendez, E., Hermoso, J., and Salas, M. (1986) Virology 155, 474-483. 27. Yoshikawa, H., Garvey, K.J., and Ito, J. (1985) Gene 37, 125-130. 15 28. Martin, A.C., Lopez, R., Garcia, P. (1998) J Bacteriol 180, 210-217. 29. Steiner, M., Lubitz, W., Blasi, U. (1993) J. Bacteriol. 175, 1038-1042. * Durfee, T., Becherer, K., Chen, P.-L., Yeh, S.-H., Yang, Y., Kilburn, A.E., Lee, 20 W.-H., and Elledge, S.J. (1993). Genes Dev. 7, 555-569. * Qiu, H., Garcia-Barrio, M.T., and Hinnebusch, A.G. (1998) Mol Cell Biol. 18, 2697-2711. 25 * Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura ,Y., and Miki, Y. (1998) Genes, Chromosomes & Cancer 21, 217-222. * Endo, T.A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., 30 Leonor N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., and Yoshimura, A. (1997) Nature 387, 921-924. " Karimova, G., Pidoux, J., Ullmann, A., Ladant, D. (1998) Proc. Natl. Acad. Sci. 95, 5752-5756. 35 e Sopta, M., Carthew, R.W., and Greenblatt, J. (1995) J. Biol. Chem. 260, 10353 10369. * Qin, J., Fenyo, D., Zhao, Y., Hall, W.W., Chao, D.M., Wilson, C.J., Young, R.A. 40 and Chait, B.T. (1997) Anal. Chem. 69, 3995-4001. e Tomasz, A. (1966) Journal of Bacteriology 91, 1050-1061. " McDonnell, M., Ronda, LC and Tomasz, A. (1975) Virology 63, 577-582. 45 e Ronda C., Lopez, R., Tomasz, A. and Portoles A. (1978) 26, 221-225.
WO 00/32825 PCT/IB99/02040 110 0 Swanstr6m, M. and Adams, M.H. (1951) Proc. Soc. Exptl. Biol. Med. 78, 372 375. Diaz E and Garcia JL. (1990) Gene 90, 163-167. 5 9 Tauriainen, S., Karp, M., Chang, W and Virta, M. (1997). Recombinant luminescent bacteria for measuring bioavailable arsenite and antimonite. Apple. Environ. Microbiol. 63:4456-4461. All patents and publications mentioned in the specification are indicative of 10 the levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually. One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, 15 as well as those inherent therein. The specific methods and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art which are encompassed within the spirit of the invention are defined by the scope of the claims. 20 It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. For example, those skilled in the art will recognize that the invention may suitably be practiced using a variety of different bacteria, bacteriophage, and sequencing methods within the general descriptions 25 provided. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms "comprising," "consisting essentially of' and "consisting of' may be replaced with 30 either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is not intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should 35 be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that-such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
WO 00/32825 PCT/IB99/02040 l11 In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group. For example, 5 if there are alternatives A, B, and C, all of the following possibilities are included: A separately, B separately, C separately, A and B, A and C, B and C, and A and B and C. Thus, for example, for the bacteria and phage specified herein, the embodiments expressly include any subset or subgroup of those bacteria and/or phage. While each such subset or subgroup could be listed separately, for the sake of brevity, such a 10 listing is replaced by the present description. Thus, additional embodiments are within the scope of the invention and within the following claims.
WO 00/32825 PCT/IB99/02040 112 Table 1 Phages against human and animal pathogenic bacteria 5 I. Pathogen Phage name 11. Cat Origin/reference name alo Acinetobacter A3/2 Felix d'Herelle Reference calcoaceticus A10/45 CentreQuebecQuebec A36 B9GP BPP BS46 E13 E14 531 Ap3 J. Bacteriol 1984. 157: 179-183 P78 J. Gen. Microbiol 1986.132: 2633-2636 Acinetobacter Felix d'Herelle Reference haemolyticus Centre,Quebec,Quebec Acinetobacter Felix d'Herelle Reference johnsonii Centre.Quebec,Quebec Acinetobacter sp. BP1 J.Virol. 1968.2:716-722 G4, HP2, HP3 & Can.J.Microbiol.1966.12:1023-1030 & HP4 J.Virol.1974.13:46-52 & Arch.Virol. 1994.135:345-354 Al, A4, A9 & Arch.Virol.1994.135:345-354 196 HP1 Can.J.Microbiol.1966.12:1023-1030 A19, A23, A29, J.Microsc (Paris) 1973.16:215-224 & A31, A33, A34, CR.Hebdo Seances Acad.Sci.Ser D.Sci A3759 & 2845 Natur(Paris)278:1907-1909 & Arch.Virol.1994.135:345-354 & Rev.Can.Biol. 1970.29:317-320 Actinobacillus FEMS Microbiol Lett 1994. 119:329-337 actinomycetecomitans WO 00/32825 PCT/IB99/02040 113 Infec. Immun. 1982. 35: 343-349 Mol.Gen.Genet 1998.258: 323-325 Aa(p247 Oral Micriol. Immunol 1997.12: 40-46 Actinomyces viscosus 43146-B 1 The American Type Culture Collection Infect.Immun. 1985.48:228-233 Infect.Immun. 1988.56:54-59 Plasmid 1997.37:141-153 Aeromonas hydrophila PM2** & PM3 FEMS Microbiol.Lett. 1990.57:277-282 Aehl Felix d'Herelle Reference Aeh2 Centre,Quebec,Quebec PM4 PM5 PM6 T7-ah WO 00/32825 PCT/IB99/02040 114 Aeromonas 3 Felix d'Herelle Reference salmonicida 25 Centre,Quebec,Quebec 29 31 32 40RR 2
.
8 t 43 51 56 59.1 65 Asp37 55R.1 Can. J. Microbiol. 1983. 29: 1458-1461 Alteromonas espejiana PM2** 27025-B , The American Type Culture Collection Asticacaulis Felix d'Herelle Reference biprosthecum Centre,Quebec,Quebec Asticcacaulis 15261-B1 The American Type Culture Collection excentricus 15261-B2 15261-B3 #Ac2l 4Ac24 Azotobacter vinelandii 12518-HI The American Type Culture Collection 125 18-B4 125 18-135 A14 12518-B9 A21 12518-BIO A31 13705-BI A41 PAVI Azotobacter sp. Virology 1972.49:439452 Bacteroidesfragilis Bf- 1 Rev. Infect. Dis. 1979. 1: 325-336 B40-8 FEMS Microbiol. Lett. 1991. 66: 61-67 HSP40 Appi. Environ. Microbiol. 1989. 55: 2696 2701 phiAl Zentralbl.bakteriol. 1972.222:57-63 Bdellovibrio MAC-i J. Gen. Microbiol. 1987. 133: 3065-3070 bacteriovorus Bdellovibrio sp. VL- I J.Virol. 1973.12:1522-1533 Bordetella 214 Zh.Mikrobiol.Epidemiol.Immuno. 1987.5:9 brochiseptica 13 WO 00/32825 PCT/IB99/02040 115 Bordetella Felix d'Herelle Reference parapertussis Centre,Quebec,Quebec Mol. Gen. Mikrobiol. Virusol. 1988.4: 22-25 Zh.Mikrobiol.Epidemiol.Immuno. 1987.5:9 13 41405 Zh.Mikrobiol.Epidemiol.Immuno. 1987.5:9 13 Brucella abortus Felix d'Herelle Reference Centre,Quebec,Quebec 23448-B1 The American Type Culture Collection 23448-B2 23448-B3 17385-Bl 17385-B2 10/I 24/11 212/XV BK-2, TB & Zh.Mikrobiol.Epidemiol.Immunobiol.1983.2: Fi** 48-52 R/c & R/O Dev. Biol. Stand. 1984.56: 55-62 Brucella canis R/c Dev. Biol. Stand. 1984.56: 55-62 Brucella melitensis BK-2 23456-B1 The American Type Culture Collection Brucella suis Wb Zentralbl.Veterinarmed. 1975.22:866-867 WO 00/32825 PCT/IB99/02040 116 Fi** & TB Zh.Mikrobiol.Epidemiol.Immunobiol.1983.2: 48-52 Brucella sp. Can. J. Vet. Res. 1989.53: 319-325 Res. Vet. Sci. 1988. 44: 45-49 R Zh.Milcrtobiol.Epidemiol.Immunobiol. 1983.2: 48 Campylobacter coli 43133-B1 The American Type Culture Collection 43 134-BI1 Campylobacter coli 18 43135-B1 The American Type Culture Collection (Cont'd) 19 43136-Bi 20 Campylobacterjejuni 1 35918-BI The American Type Culture Collection 2 35919-Bl 3 35920-Bl1 4 35921-Bl 5 35918-B2 6 35920-B2 7 35922-132 8 35923-BI 9 35924-Bl 10 35925-BI 11 35925-B2 12 35922-B2 13 35924-B2 14 35922-B3 17 43133-Bl 18 43134-BI 19 43135-Bl 20 43136-Bl Campylobacter HP 1 J. Med. Microbiol.1993. 38: 245-249 (Helicobacter) pylori Chlamydia psittaci Chpl* I. Gen. Virol. 1989. 70: 3381-3390 Clostridium CAK- 1 J.Bacteriol. 1993.175:3838-3843 acetobutvicum ________ __________________________ WO 00/32825 PCT/IB99/02040 117 Clostridium botulinum Nucleic Acids Res.1990.18:1291 Bioch.Biophys.res.Commun.1990.171.1304 1311 Microbiol.immunol. 1981.25:915-927 J.Vet.Med.Sci. 1992.54:675-684 CEOp &CE y Clostridium difficile 41 & 56 J. Clini.Microbiol. 1985.21:251-254 WO 00/32825 PCT/IB99/02040 118 Clostridium Rev.Can.Biol. 1977.36:205-215 perfringens FEMS Microbiol.Lett. 1990.54:323-326 Clostridium 8074-B 1 The American Type Culture Collection sporogenes 59 17886-B1 70 17886-B3 71 17886-B4 72S 17886-B5 72L 17886-B6 Clostridium tetani A & B Rev.Can.Biol.1978.37:43-46 Corynebacterium Vopr.Virusol. 1986.31:577-584 diphteriae Corynebacterium NN 12319-B1 The American Type Culture Collection pseudotuberculosis Corynebacterium sp DLC 2921/49 12052-B1 The American Type Culture Collection WO 00/32825 PCT/IB99/02040 119 Enterococcus faecalis 42 19948-B1 The American Type Culture Collection Enterococcusfaecium 19950-B 1 The American Type Culture Collection 19953-b2 19953-B1 124 133 WO 00/32825 PCT/IB99/02040 120 Escherichia coli 11303-B14 The American Type Culture Collection 11303-BlO 11303-B21 8677-B1 11303-B13 13706-B4 Escherichia coli 15766-B1 The American Type Culture Collection (Cont'd) 15766-B1 1242-B5 15669-B2 15767-BI 11303-B16 27-65-B1 25065-B2 C204 15669-BI El 15597-BI fl** 21816-B1 f2** 23724-B9 FCZ 15593-Bl fd** 25404-B 1 29746-BI 23631-B1 25868-B1 25298-B1 25298-B2 11303-B37 11303-B24 Ifl** 11303-B26 11303-B27 11303-B28 11303-B29 11303-B30 11303-B33 11303-B31 11303-B25 11303-B35 MS2** 11303-B34 MU9 11303-B36 Mu-I 11303-B32 Ox6 13706-B5 P1** 11303-BI P4 sidi** 11303-B2 11303-B3 R17** 11303-B4 ZlK/1 35060-B1 ZJ/2 35060-B2 35060-B3 11303-B5 11303-B6 11303-B7 11303-B38 12141-B1 WO 00/32825 PCT/IB99/02040 121 Escherichia coli 11303-B20 The American Type Culture Collection (Cont'd) 11303-B17 11303-B15 11303-B1l 547 11303-B18 Uvi 13706-B2 UV47 23724-B2 UV375 23724-BI a3** 23724-B3 x *23724-B4 X C-17 23724-B5 X sus P-3 23724-B6 X sus R-5 23724-B7 X sus J-6 23724-B8 X sus 0-8 35860-B1 X sus A-11 13706-B3 kind- 15597-B2 #92 13706-BI #R 49696-B1 #V-1 #X174** $Xcs70am-3 G4** & K** Biochim.Biophysica Acta.1992.1130:277-288 BF23** J.Bacteriol. 1977.129:265-275 Mul J.Ultrastruct.Res. 1966.14:441-448 Hp17 J.Mol.Biol. 1991.218:705-721 K3** & Ox2** FEBS Lett.1987.215:145-150 Rbl8**, Rb5l & J.Bacteriol.1990.172:180-186 Rb69** H1**, H3, H8, Mol.Gen.Genet. 1990.221:491-494 K9, K18 & Oxl Ml**, TuIa** & J.Mol.Biol. 1987.196:165-174 TuIb** KIO0______ J.Bacteriol. 1979.140:680-686 Qsr' J.Bacteriol. 1985.162:256-262 B278 J.Gen.Microbiol.1988.134:1333-1338 phi 80** FEMS Microbiol.Left.1994.119:71-76 phi m173 Genetika 1985.21:673-675 tf- 1 J.Gen.Microbiol. 1987.133:953-960 P4 & phiR73 Mol.Microbiol.1995.18:201-208 12-2 J.Gen.Microbiol. 1982.128:2797-2804 PRD1 Virology 1990.177:445-451 K3hx Mol.Gen.Genet.1987.206:110-115 933J**& Infect.Immunity.1986.53:135-140 933W** H19-B** J.Bacteriol. 1987.169:4308-4312 Tcp-l I1 Zentralbnl.Bakteriol.Mikrobiol.Hyg. 1988.270: 41-51 WO 00/32825 PCT/IB99/02040 122 N4** Vet.Microbiol.1992.30:203-212 Phi 80 trp Ann.Inst.Pasteur. 1971.120:121-125 Obeta I J.Bacteriol. 1978.133:172-177 P1CM J.Gen.Microbiol.1978.107:73-83 PA-2** J.Bacteriol. 1990.172:1660-1662 186** Mol.Gen.Genet. 1982.187:87-95 186.IX.B Mol.Microbiol. 1992.6:2629-2642 21** Virology 1983.129:484-489 P4** MicrobiolRev. 1993.57:683-702 82** J.Biol.Chem. 1987.262:11721-11725 PSP3 J.Bacteriol. 1996.178:5668-5675 HK022** Nucleic Acids Res. 1994.22:354-356 D108** Nucleic Acids Res. 1986.14:3813-3825 Escherichia coli Rb49 J.Mol.Biol.1997.267:237-249 (Cont'd) Ike** J.Mol.Biol. 1985.181:27-39 P22dis Mol.Gen.Genet. 1978.166:233-243 N15** J.Bacteriol. 1996.178:1484-1486 Ifl** Proc.R.Soc.Lond.B.Biol.Sci. 1991.245:23-30 Stx2Phi-I & Infect.Immun. 1998.66:4100-4107 Stx2Phi-II 18 Virology 1987.156:122-126 X J.Gen.Microbiol.1981.126:389-396 AC3 Mol.Microbiol. 1991.5:715-725 WO 00/32825 PCT/IB99/02040 123 BW- 1 Felix d'Herelle Reference C-1 Centre,Quebec,Quebec E920g Esc-7-11 H19J Haiti HK243 Ia K20 K30
KL
3 M Mu** 0103 0157:H7 PID Pt1 PilHa PR64FS PR772 SS4 p4Q kvir** 928 09-1 92 Haemophilus HPl** Nucleic Acids Res. 1996.24:2360-2368 influenzae S2** Gene 1997. 196: 139-144 Halobacterium S45 Felix d'Herelle Reference cutirubrum Centre,Quebec,Quebec Halobacterium Felix d'Herelle Reference halobium Centre,Quebec,Quebec Can.J.Microbiol. 1982.28:916-921 Halobacterium Biol.Chem.Hoppe Seyler 1994.375:747-757 salinarium WO 00/32825 PCT/IB99/02040 124 Klebsiella oxytoca tf- I J.Gen.Microbiol. 1987.133:953-960 Klebsiella pneumoniae 60 23356-B1 The American Type Culture Collection 92 23357-B1 K19Q Felix d'Herelle Reference Centre,Quebec,Quebec FC3-1 & FC3-9 Can.J.Microbiol. 1991.37:270-275 FC3-10 FEMS Microbiol.Lett. 1991.67:291-297 Klebsiella sp. K1l** Mol.Gen.Genet. 1990.221:283-286 Leptospira sp. LEJ, LE3 & LE4 Res.Microbiol.1990.141:1131-1138 Listeria 243 23074-B 1 The American Type Culture Collection monocytogenes 197,C1313 & Appl.Environ.Microbiol. 1997.63:3374-3377 9425 H387 & H387-A Appl.Environ.Microbiol.1993.59:2914-2917 5775,6223 APMIS.1993.01:160-167 & 12682 ____________________ 2389, 2671, Intervirology 1994.37:31-35 & 4211 & 2685 Zentralbl.Bakteriol.Mikrobiol.Hyg.1986.261: 2-28 4b,4ab, 4g & 3c Ann.Microbiol (Paris) 1977.128:185-198 A 118, A500 & Mol.Microbiol. 1995.16:1231-1241-992 A511** 1, 3, 4, 5, 6, 7, 8, Ann.Microbiol. (Paris) 1979.130B:179-189 9,10,11, 14,15, 16, 17, 19 & 20 1/2a, 1/2b, 3c, Clin.Invest.Med. 1984.7:229-232 4ab, 6a & 6b #LMUP35 Felix d'Herelle Reference 2685 Centre,Quebec,Quebec Listeria innocua 4211 Felix d'Herelle Reference Centre,Quebec,Quebec Micrococcus luteus 4698-B1 The American Type Culture Collection 4698-B4 N3 4698-2 N4 4698-B3 N8 Micrococcus luteus N17 Can.J.Microbiol. 1979.25:1027-1035 Mycobacterium BK-3 27203-B1 The American Type Culture Collection smegmatis Bol** 27204-B1 Bo 6 27205-BI Bo 611 27205-B2 Bo 6111 27205-B3 Mc-2 607-B6 Mc-4 607-B7 NN 11727-B1 Phagus lacticola 11759-B1 RI 607-B1 WO 00/32825 PCT/IB99/02040 125 HER 317 Felix d'Herelle Refrence HER 330 Centre,Quebec,Quebec HER 333 HER 335 HER 334 HER 331 HER 316 Legendre Leo Roy Sedge Mol.Microbiol. 1993.7:395-405 J.Mol.Biol. 1998.279:143-164 Proc.Natl.Acad.Sci USA. 1988.84:2833-2837 Mol.Biol.Rep. 1981.30:11-15 Proc.Natl.Acad.Sci.USA 1997.94:10961 10966 29M, 31M, 122, Arch.Virol.1993.133:39-49 & 154, 37, 29D, 46, Am.Rev.Respir.Dis. 1975.112:17-22 139,110, 141, 74D, AGI & DS6A Mycobacterium 23052-B1 The American Type Culture Collection fortuitum 27207-B 1 Bo 4 27207-B2 Bo 7 WO 00/32825 PCT/IB99/02040 126 Mycobacterium leprae Ann.Microbiol. (Paris) 1982.133:93-97 Mycobacterium 25618-B1 The American Type Culture Collection tuberculosis 25618-B2 DS6A 4243-B1 110, 139 & 33D Arch.Virol.1993.133:39-49 AG1,GS4E, The Biology of Mycobacteria.Academic BG1, Press,Toronto 1982 (Ratledge & Stanford) PH & BK1 1982.309-351 Mycobacterium sp Phagus pellegrini 11760-B1 The American Type Collection Culture NN 11761-B1 BI 23239-BI WO 00/32825 PCT/IB99/02040 127 TM4, ph60, Microbiology 1995.141:1173-1181 ph72, PhAE39, phAE40 & Bxbl C2 Experentia 1969.25:1112-1113 18 & 115 J.Gen.Virol.1987.68:949-956 63 Gruzlica 1968.36:617-622 phlei & J.Gen.Virol.1975.29:235-238 butyricum MyF3P-59a Z.Allg.Mikrobiol.1968.8:29-37 Bo2a J.Gen.Virol. 1973.20:75-87 D4,D28 & D32 J.Exptl.Med.1966.123:327-340 HC J.Bacteriol. 1963.86:608-609 Mycobacterium B5 15483-BI The American Type Culture Collection vaccae Mycobacterium phlei 11728-B1 The American Type Culture Collection 11758-B1 NN 27086-B2 Bo 2 27086-B 1 Bo 2h Bo 3 Mycoplasma MAV1** Infect.Immunity. 1995.63:4016-4023 arthritidis Mycoplasma hyorhinis Hr-1 Arch.Virol. 1983.77:81-85 Mycoplasma Br-1 Arch.Virol. 1983.75:1-15 pneumonae Mycoplasma pulmonis Plasmid 1995. 33: 41-49 Mycoplasma sp. J.Gen.Microbiol. 1985:131:3117-3126 J. Virol.1986.59:584-590 Gene 1994. 141: 1-8 WO 00/32825 PCT/IB99/02040 128 Microbios 1990. 64: 111-125 Infection& Immunity 1995. 63: 4016-4023 Med.Biol.1982.60:116-120 MV-L2 & Arch.Virol.1979.61:289-296 Acta.Virol. 1978.22:443-450 J.Gen.Virol.1979.42:315-322 Virology 1973.55:118-126 WO 00/32825 PCT/IB99/02040 129 Science 1971.173:725-727 Neisseria perflava J.Clin.Microbiol.1976. 4:87-91 Nocardia erythrypolis pC J.Gen.Virol. 1974.23:247-254 pEC J.Bacteriol. 1976.126:1104-1107 Pasteurella multocida B225 Arch.Exp.Veterinarmed. 1981.35:433-436 B939a Am.J.Vet.Res.1978.39:1565-1566 Nos.115, 32, 967 Vet.Med.Nauki. 1977.14:33-36 & 1075 Propionibacterium NN 29399-BI The Amecan Type Collection Culture acnes WO 00/32825 PCT/IB99/02040 130 Pseudomonas 12175-B 1 The American Type Culture Collection aeruginosa 2 12175-B2 2A 12175-B3 2B 12175-B4 11 14205-B1 16 14206-B1 24 14207-B1 27 14208-B1 44 14209-B 1 73 14210-BI 95 14211-B1 109 14212-B1 113 14213-B1 249 14214-BI B3 15692-B1 Hoff 2 14203-B1 Hoff 3 14204-B1 Pa 12055-B1 Pb 12055-B2 PB-1 15692-B3 Pc 12055-B3 Pf 25102-BI pp7** 15692-B2 Felix d'Herelle Reference Centre,Quebec,Quebec 7 & 31 Pf3** J.Virol. 1983.47:221-223 p-MC Can.J.Microbiol. 1969.15:1179-1186 Pfl** J.Mol.Biol. 1991.218:349-364 PR4** J.Gen.Virol. 1979.43:583-592 A7 J.Bacteriol.1992.174:2407-2411 KFI J.Biochem.1983.93:61-71 _CTX** Mol.Microbiol.1993.4:1703-1709 f2** J.Virol.1977.24:135-141 WO 00/32825 PCT/IB99/02040 131 pKZ, 21, pNZ, dd( PMN17, PTB80, 68, PB-i, E79, 16, 109, 352, 1214, F8, 71, 337, M4, pC17, SL2, B17, Li-24, <pmnP78, PS17**, 91, 73, M6, Li-2, 7, ymnF82, PTB2, PTB20, PTB42, pKF77, 31, PTB21, 119x, (pPLS27, B3, 258, Hwl2, PM57, PM62, PM105, 148, PM681, 198, 218, 222, 242, 246, PC131, pC11, SL5, D3112**, Jbl9, F7, PM69, PM13, PM61, PM 113, (p240, 249 & 269 WO 00/32825 PCT/IB99/02040 132 Pseudomonas 297, 309, 318, Arch.Virol.1993.131:141-151 aeruginosa 11, (Cont'd) WO 00/32825 PCT/IB99/02040 133 Pseudomonas cepacia Felix d'Herelle Reference Centre,Quebec,Quebec Pseudomonasfragi 27362-B1 The American Type Culture Collection 27363 B1 WY Pseudomonas #6 Felix d'Herelle Reference phaseolicola Centre,Quebec,Quebec Pseudomonas putida gh-I 12633-B1 The American Type Culture Collection Pseudomonas syringae 40492-B1 The American Type Culture Collection 21781-B1 #-6 Pseudomonas sp. PPs-G3 49780-B1 The American Type Culture Collection Salmonella bareilly Sab 2 Felix d'Herelle Reference Centre,Quebec,Quebec Salmonella enteritidis 1, 2,3 & 6 Epidemiol.Infect.1995.114:227-236 2a, 3a, 4a, 5a, 6a, Vet.Med.Nauki.1975.12:55-60 7a, 8a, 9a, 15, 19, 20 &21** Salmonella newington Epsilon 34 J.Struct.Biol. 1995.115:283-289 Salmonella newport 27869-B1 The American Type Culture Collection 27869-B2 16-19 Felix d'Herelle Reference Centre,Quebec,Quebec Salmonella paratyphi 19940-B 1 The American Type Culture Collection 12176-B1 Paratyphoid A Jersey Felix d'Herelle Reference Centre,Quebec,Quebec Salmonella SasLI, SaL2, Sal Indian J.Med.Res. 1997.105:47-52 senftenberg 3, SaL4, SaL5 & SasL6 Salmonella P22** 19585-B1 The American Type Culture Collection typhimurium SL-1 40282 MB78** J.Virol. 1982.41: 1038-1043 SEl J.Gen.Microbiol.1986.132:1035-1-41 LT2 Virology 1971.45:835-636 ES18** Virology 1970.42:621-632 L** J.Virol.1985.56:1034-1036 WO 00/32825 PCT/IB99/02040 134 P1CM clr-100 Mol.Gen.Genet.1975.138:1 13-126 F22 Genet.Res. 1986.48:139-143 Fels 1 J.Gen.Virol.1978.38:263-272 Fels 2 Genet.Res.1986.48:139-143 Px Mol.Gen.Genet.1970.108:184-202 Plkc Virology 1974.60:503-514 A3 &A4 J.Bacteriol. 1987.169:1003-1009 HT Genet.Res. 1976.27:315-322 Salmonella IRA J.Basic Microbiol. 1990.30:707-716 typhimurium Mud1 Mol.Gen.Genet. 1986.202:327-330 (Cont'd) P22 (cir4-1, cir5- Mol.Gen.Genet. 1984.198:105-109 1 & cir6-1) BF23** Mol.Gen.Genet. 1976.147:195-202 Kbl J.Bacteriol.1974.117:907-908 P221dis J.Gen.Virol. 1978.41:367-376 PRD1** Virology 1990.177:445-451 122** J.Gen.Microbiol. 1982.128:2797-2804 tf- 1 J.Gen.Microbiol. 1987.133:953-960 X** J.Gen.Microbiol. 1981.126:389-396 Salmonella 8 19937-BI The American Type Culture Collection typhosa/typhi 23 19938-B1 25 19939-BI 46 19942-Bl 53 19943-BI 163 19946-B1 175 19947-BI Vii 27870-B 1 ViVI 27870-B2 01 Felix d'Herelle Refrence Centre,Quebec,Quebec ViII Chung Hua Liu Hsing Ping H.T.C.1992.13:288 j2 J.Gen.Microbiol. 1983.129:3395-33400 Salmonella sp. P3 25957-B1 The American Type Culture Collection P4** 25957-B2 P9a 25957-B3 P9c 25957-B4 PlO 25957-B5 102 19945-BI Chi (x) 9842-B1 R34 97541 MG40 Virology 1968.34:521-530 P14 Microb.Pathog.1990.8:393-402 PSP3 Virology 1992.188:414 Ike** Zentralbl.Bakteriol. 1976.234:294-304 P27 & 9NA J.Virol.1986.12:921-931 Sphaerotilus natans SN1 Appl.Environ.Microbiol. 1979.37:1025-1030 WO 00/32825 PCT/IB99/02040 135 Shigella dysenteriae 23351-B1 The American Type Culture Collection P2 11456b 0-80 11456a-Bl Shigellaflexeneri D20 12661-Bl The American Type Culture Collection SflI** Mol.Microbiol. 1997.26:939-950 SfV** Gene 1997.22:217-227 Sf6** Mol.Microbiol. 1995.18:201-208 SfX Gene 1993.129:99-101 Shigella sonnei C16** Ufa Mol..Biol (Mosk) 1977.11:323-331 Shigella sp 37 23354-B1 The American Type Culture Collection Spiroplasma citri SpV 1 Plasmid 1993.29:193-205 Spiroplasma sp. SpV1-R8A2B Nucleic Acids Res. 1990.18:1293 SpV3 Isr.J.Med.Sci. 1987.23:429-433 Sp V4 J.Bacteriol. 1987.169:4950-4961 Staphylococcus albus Staphylococci & Staphylococcal Infections. 1997. Voll:503-508 (KargerBasel) WO 00/32825 PCT/IB99/02040 136 Staphylococcus aureus 27702-B 1 The American Type Culture Collection 27703-B1 27704-B 1 23360-B1 23361-B1 15 27705-BI 17 27712-B1 29 27690-BI 42D** 27691-B1 42E 27692-B1 47 27693-B1 52 27694-B1 52A 27695-BI 53 27696-Bl 54 27697-B1 55 27698-BI 71 27699-B1 75 27693-B2 77 27700-B1 79 27701-BI 80 27706-BI 81 27707-BI 83A 27708-B1 84 33742 85** 33741-B1 88 15565 92 19685-B1 5504' 11987-Bl K 11988-BI P1 15752-Bl P14 UC18 WO 00/32825 PCT/IB99/02040 137 HER 101 Felix d'Herelle Reference HER 239 Centre,Quebec,Quebec HER 283 HER 49 Twort** #11** J.Bacteriol. 1988.170:2409-2411 413** & 442** J.Gen..Microbiol.1989.135:1679-1697 L54a** J.Bcteriol. 1986.166:385-391 80a** Can.J.Microbiol. 1996.43:612-616 94,95 & 96 J.Clin.Microbiol. 1988.26:2395-2401 p13 1,A 3 & A 5 Staphylococci & Staphylococcal Infections. 1997. Voll:503-508 (KargerBasel) Phi PVL** Gene 1998.215:57-67 Staphylococcus BaSTC2 Felix d'Herelle Reference carnosus Centre,Quebec,Quebec Staphylococcus la, 2b, 3a, 4b, Can.J.Microbiol. 1988.34:1358-1361 epidermidis 5a, 6b, 7b, 8c, 9a, 10a, 1lb,12a & 13b 41, 63, 11811, Res.Virol.1994.145:111-121 138, 245, 336, 392 & 550 Staphylococcus 1154A, 1405, Res.Virol.1990.141: 625-635 & saprophyticus 1314, 1139 & Res.Virol.1994.145:111-121 1259 Staphylococcus sp. Phi 812, Phi 131, Virology 1998.246:241-252 SK311 & U16 Streptococcusfaecalis VD13 HER44 Felix d'Herelle Reference Centre,Quebec,Quebec Streptococcus faecium PEl Zentralbl.Bakteriol. 1975.231:421-425 Streptococcus oralis Cp-1** & Cp- FEMS Microbiol.Lett.1989.65:187-192 7** WO 00/32825 PCT/IB99/02040 138 Streptococcus Cp-1** HER223 Felix d'Herelle Reference pneumoniae Centre,Quebec,Quebec Cp-1**, Cp-5**, J.Virol.1981.40:551-559 & Cp-7**, Cp-9**, Eur.J.Biochem.1979.101:59-64 & o-1 & o-2 Microbial Drug Resistance 1997.3:165-176 HB-623 & HB- J.Virol. 1990.64:5149-5155 746 EJ -1** J.Bacteriol. 1992.174:5516-5525 Dp-2 & Dp-4 J.Virol.1978.26:221-225 Dp-1 Virology 1975.63:577-582 o-3 & o-8 J.Virol. 1976.19:659-667 304 J.Bacteriol.1980.141:1298-1304 HB-1,HB-2, J.Bacteriol. 1979.138:618-624 HB-3**, HB-4, HB-5 & HB-6 Streptococcus T12** Mol. Microbiology. 1997#23:719-728 pyogenes A-1 12202-B1 The American Type Culture Collection A-6 12203-Bl A-25 12204-BI Kjem 14918 Streptococcus I HER 339 Felix d'Herelle Refrence sp.lEnterococcus 182 HER 80 Centre,Quebec,Quebec VD1884 HER 323 1A 12169-BI The American Type Culture Collection 1B 12170-BI NN 21597-B1 42 19948-BI 118 19951-B2 120 19952-BI Veillonella rodentium N2 Antonie Van Leeuwenhoek 1989.56:263-271 Vibrio cholerae Psi 92 Intervirology 1993.36:237-244 VCB-1,2,3 & 4 J.Infetion 1998.36:131 CP-T1** J.Virol. 1984.51:163-169 VSK FEMS Microbiol.Lett.1996.145:17-22 Phil38 J.Virol.1986.57:960-967 Phil49 J.Virol.1985.140:217-223 Fs-2** Microbiology 1998.144:1901-1906 WO 00/32825 PCT/IB99/02040 139 e4 Felix d'Herelle Reference e5 Centre,Quebec,Quebec X29 K 13 14 16 24 32 57 Vibrio cholerae 138 14100-B 1 The American Type Culture Collection (Cont'd) 145 14100-B2 149 14100-B30 163 14100-B4 N-4 51352-Bl S-5 51352-B2 S-20 51352-B3 M-4 51352-B4 D-10 51352-B5 I 51352-b6 II 51352-B7 III 51352-B8 IV 51352-B9 V 51352-BlO Vibrio costicola UTAK Felix d'Herelle Reference Centre,Quebec,Quebec Vibrio eltor e 4 J.Gen.Virol. 1987.68:1411-1416 Vibrio natrigens ntl,nt6 Felix d'Herelle Reference Centre,Quebec,Quebec Vibrio KVP40** Felix d'Herelle Reference parahaemolyticus VF33 Centre,Quebec,Quebec VPl #60 4HAWI-5 $PEL8C-1 Vibrio sp. a3a Felix d'Herelle Reference Centre,Quebec,Quebec NN 11985-B1 The American Type Culture Collection phl 51582-BI Phil49 J.Virol. 1987.61:3999-4006 Veillonella rodentium N2 Antonie V.Leeuwenhoek. 1989.56:263-271 WO 00/32825 PCT/IB99/02040 140 Yersinia enterocolitica 1 Felix d'Herelle Reference 2 Centre,Quebec,Quebec 3 4 5 6 7 8 9 4YeO3-12 I, IV & VIII Zentralbl.Bakteriol.Mikrobiol.Hyg.1982.253:1 02 Yersinia pestis R 23208-B 1 The American Type Culture Collection S 11593-BI Y 23053-B1 II Zh.Mikrobiol.Epidemiol.Immunobiol. 1990.11 :9 Yersinia PST** 23207-B 1 The American Type Culture Collection pseudotuberculosis Yersinia sp. RD2 Mol.Gen.Mikrobiol.Virusol.1990.8:18-21 xxxx) WO 00/32825 PCT/IB99/02040 141 Table 2 >Bacteriophage 77, complete genome sequence, 41708 nucleotides 1 gatcaaaata cttggggaac ggttagggag taaacttcgc gataatttta aaaattcatg 61 tataaccccc ctcttataac cattttaagg caggtgatga aatggagatt atagtcgatg 121 aaaatttagt gcttaaagaa aaagaaaggc tacaagtatt atataaagac atacctagca 181 ataaattaaa agtagttgat ggtttaatta ttcaagcagc aaggctacgt gtaatgcttg 241 attacatgtg ggaagacata aaagaaaaag gtgattatga tttatttact caatctgaaa 301 aggcgccacc atatgaaagg gaaagaccag tagccaaact atttaatgct agagatgctg 361 catatcaaaa aataatcaaa caattatcgg atttattgcc cgaagagaaa gaagacacag 421 aaacgccatc tgatgattac ctatgattag taataaatac gttgatgaat atataaattt 481 gtggaaacaa ggaaagataa ttttaaataa agaaagaatt gatctcttta attatctaca 541 aaaacatata tattcacgag atgatgtata ttttgatgaa cagaaaatcg aggattgtat 601 caaatttatt gaaaaatggt attttccaac attaccattt caaaggttta tcatagctaa 661 tatatttctt atagataaaa atacagatga agctttcttt acagaatttg ctattttcat 721 gggacgtgga ggcgggaaaa acggtctaat aagtgctatt agtgattttc tttctacgcc 781 cttacacgga gttaaagaat atcacatctc cattgttgct aatagtgaag atcaagcaaa 841 aacatcgttt gatgaaatca gaaccgtttt aatggataac aaacgaaata agacgggtaa 901 aacgccaaaa gctccttatg aagttagtaa agcaaaaata ataaaccgtg caactaaatc 961 ggttattcga tataacacat caaacacaaa aaccaaagac ggtggacgtg aggggtgtgt 1021 tatttttgat gaaattcatt atttctttgg tcctgaaatg gtaaacgtca aacgtggtgg 1081 attaggtaaa aagaaaaata gaagaacgtt ttatataagt actgatggtt ttgttagaga 1141 gggttatatc gatgcaatga agcacaaaat tgcaagtgta ttaagtggca aggttaaaaa 1201 tagtagattg tttgcttttt attgtaagtt agacgatcca aaagaagttg atgacagaca 1261 gacgtgggaa aaggcgaacc caatgttaca taaaccgtta tcagaatacg ctaaaacact 1321 gctaagcacg attgaagaag aatataacga tttaccattc aaccgttcaa ataagcccga 1381 attcatgact aagcgaatga atttgcctga agttgacctt gaaaaagtaa tagcaccatg 1441 gaaagaaata ctagcgacta atagagagat accaaattta gataatcaaa tgtgtattgg 1501 tggtttagac tttgcaaaca ttcgagattt tgcaagtgta gggctattat tccgaaaaaa 1561 cgatgattac atttggttag gacattcgtt tgtaagacaa gggtttttgg atgatgtcaa 1621 attagaacct cctattaaag aatgggaaaa aatgggatta ttgaccattg tcgatgatga 1681 tgtcattgaa attgaatata tagttgattg gtttttaaag gctagagaaa aatatgggct 1741 tgaaaaagtc atagctgata attatagaac tgatattgta agacgtgcgt ttgaggatgc 1801 tggcataaaa cttgaagtac ttagaaatcc aaaagcaata catggattac ttgcaccacg 1861 tatcgataca atgtttgcga aacataacgt aatatatgga gacaatcctt tgatgcgttg 1921 gtttactaat aatgttgctg taaaaatcaa gccggatgga aataaagagt atatcaaaaa 1981 agatgaagtc agacgtaaaa cggatggatt catggctttt gttcacgcat tatatagagc 2041 agacgatata gtagacaaag acatgtctaa agcgcttgat gcattaatga gtatagattt 2101 ctaatagagg aggtgagaca tgagtattct agaaaagata tttaaaacta ggaaagatat 2161 aacatatatg cttgatttag atatgataga agatctatca caacaagcgt atgtgaaacg 2221 tttagcgatt gatagttgta ttgaatttgt tgcgcgagct gtcgctcaaa gtcattttaa 2281 agtattggaa ggtaatagaa ttcaaaagaa tgatgtttac tacaagttaa atataaaacc 2341 aaatactgac ttatcaagcg atagtttttg gcaacaagtt atatataaac taatttatga 2401 taacgaggtt ttaatcgtag taagtgacag caaagaatta cttatcgcag atagctttta 2461 cagagaagag tacgctttgt atgatgatat attcaaagat gtaacggtta aagattatac 2521 ttatcaacgt actttcacaa tgcaagaggt catatattta aagtacaaca acaataaagt 2581 gacacacttt gtagaaagtc tattcgaaga ttacgggaaa atattcggaa gaatgatagg 2641 tgcacaatta aaaaactatc aaataagagg gattttgaaa tctgcctcta gcgcatatga 2701 cgaaaagaat atagaaaaat tacaagcgtt cacaaataaa ttattcaata cttttaataa 2761 aaatcaacta gcaatcgcgc ctttgataga aggttttgat tatgaggaat tatctaatgg 2821 tggtaagaat agtaacatgc ctttttctga attgagtgag ctaatgagag atgcaataaa 2881 aaatgttgcg ttgatgattg gtatacctcc aggtttgatt tacggagaaa cagctgattt 2941 ggaaaaaaac acgcttgtat ttgagaagtt ctgtttaaca cctttattaa aaaagattca 3001 gaacgaatta aacgcgaaac tcataacaca aagcatgtat ttgaaagata caagaataga 3061 aattgtcggt gtgaataaaa aagacccact tcaatatgct gaagcaattg acaaacttgt 3121 aagttctggt tcatttacaa ggaatgaggt gcggattatg ttaggtgaag aaccatcaga 3181 caatcctgaa ttagacgaat acctgattac taaaaactac gaaaaagcta acagtggtga 3241 aaatgatgaa aaagaaaaag atgaaaacac tttgaaaggt ggtgatgaag atgaaagcgg 3301 agattaaagg cgtcatcgtt tccaacgaag ataaatgggt ttacgaaatg cttggtatgg 3361 attcgacttg tcctaaagat gttttaacac aactagaatt tagtgatgaa gatgttgata 3421 ttataattaa ctcaaatggt ggtaacctag tagctggtag tgaaatatat acacatttaa 3481 gagctcataa aggcaaagtg aatgttcgta tcacagcaat agcagcaagt gcggcatcgc 3541 ttatcgcaat ggctggtgac cacatcgaaa tgagtccggt tgctagaatg atgattcaca WO 00/32825 PCT/IB99/02040 142 3601 atccttcaag tattgcgcaa ggagaagtga aagatctaaa tcatgctgca gaaacattag 3661 aacatgttgg tcaaataatg gctgaggcat atgcggttag agctggtaaa aacaaacaag 3721 aacttataga aatgatggct aaggaaacgt ggctaaatgc tgatgaagcc attgaacaag 3781 gttttgcgga tagtaaaatg tttgaaaacg acaatatgca aattgtagca agcgatacac 3841 aagtgttatc gaaagatgta ttaaatcgtg taacagcttt ggtaagtaaa acgccagagg 3901 ttaacattga tattgacgca atagcaaata aagtaattga aaaaataaat atgaaagaaa 3961 aggaatcaga aatcgatgtt gcagatagta aattatcagc aaatggattt tcaagattcc 4021 ttttttaata caaaaatagg aggtcataaa atgactataa atttatcgga aacattcgca 4081 aatgcgaaaa acgaatttat taatgcagta aacaacggtg aaccgcaaga aagacaaaat 4141 gaattgtacg gtgacatgat taaccaacta tttgaagaaa ctaaattaca agcaaaagca 4201 gaagctgaaa gagtttctag tttacctaaa tcagcacaaa ctttgagtgc aaaccaaaga 4261 aatttcttta tggatatcaa taagagtgtt ggatataaag aagaaaaact tttaccagaa 4321 gaaacaattg atagaatctt cgaagattta acaacgaatc atccattatt agctgactta 4381 ggtattaaaa atgctggttt gcgtttgaag ttcttaaaat ccgaaacttc tggcgtggct 4441 gtttggggta aaatctatgg tgaaattaaa ggtcaattag atgctgcgtt cagtgaagaa 4501 acagcaattc aaaataaatt gacagcgttt gttgttttac caaaagattt aaatgatttt 4561 ggtcctgcgt ggattgaaag atttgttcgt gttcaaatcg aagaagcatt tgcagtggcg 4621 cttgaaactg cgttcttaaa aggtactggt aaagaccaac cgattggctt aaaccgtcaa 4681 gtacaaaaag gtgtatcggt aactgatggt gcttatccag agaaagaaga acaaggtacg 4741 cttacatttg ctaatccgcg cgctacggtt aatgaattga cgcaagtgtt taaataccac 4801 tcaactaacg agaaaggtaa atcagtagcg gttaaaggta atgtaacaat ggttgttaat 4861 ccgtccgatg cttttgaggt tcaagcacag tatacacatt taaatgcaaa tggcgtatat 4921 gttactgctt taccatttaa tttgaatgtt attgagtcta cagttcaaga agcaggtaag 4981 gttttaacgt acgttaaagg tctatatgat ggttatttag ctggtggtat taatgttcag 5041 aaatttaaag aaacacttgc gttagatgat atggatttat acactgcaaa acaatttgct 5101 tacggcaaag cgaaagataa taaagttgct gctgtttgga aattagattt aaaaggacat 5161 aaaccagctt tagaagatac cgaagaaaca ctataaaatt ttatgaggtg ataaaatggt 5221 gaaatttaaa gttgttagag aatttaaaga catagagcac aatcaacaca agtacaaagt 5281 aggggagttg tatccagctg aagggtataa caatcctcgt gttgaattgt tgacaaatca 5341 aatcaaaaat aagtacgaca aagtttatat cgtaccttta gataagctga caaaacaaga 5401 attattagaa ctatgcgaat cattacaaaa aaaagcgtct agttcaatgg ttaaaagtga 5461 aatcatcgac ttattgaatg gtgaagacaa tgacgattga tgatttgctt gtcaaattta 5521 aatcacttga aaagattgac cataattcag aggatgagta cttaaagcag ttgttaaaaa 5581 tgtcgtacga gcgtataaaa aatcagtgcg gagtttttga attagagaat ttaataggtc 5641 aagaattgat acttatacgc gctagatatg cttatcaaga tttattagaa cacttcaacg 5701 acaattacag acctgaaata atagattttt cgttatctct aatggaggta tcagaagatg 5761 aagaaagtgt ttaagaaacc tagaattaca actaaacgtt taaatacgcg tgttcatttt 5821 tataagtata ctgaaaataa tggtccagaa gctggagaaa aagaagaaaa attattatat 5881 agctgttggg cgagtattga tggtgtctgg ttacgtgaat tagaacaagc tatctcaaac 5941 ggaacgcaaa atgacattaa attgtatatt cgtgatccgc aaggtgatta tttacccagt 6001 gaagaacatt atcttgaaat tgaatcaaga tatttcaaaa atcgtttgaa tataaagcaa 6061 gtatcaccag atttggataa taaagacttt attatgattc gcggaggata tagttcatga 6121 gtgtgaaagt gacaggtgat aaagcattag aaagagaatt agaaaaacat tttggcataa 6181 aagagatggt aaaagttcaa gataaggcgt taatagctgg tgctaaggta attgttgaag 6241 aaataaaaaa acaactcaaa ccttcagaag actcaggagc actgattagt gagattggtc 6301 gtactgaacc tgaatggata aaggggaaac gtactgttac aattaggtgg cgtgggcctt 6361 ttgaacgatt tagaatagta catttaattg aaaatggtca tgttgagaaa aagtcaggaa 6421 aatttgtaaa acctaaagct atgggtggga ttaatagagc aataagacaa gggcaaaata 6481 agtattttga gacgctaaaa agggagttga aaaaattgtg attgatattt tgtacaaagt 6541 tcatgaagtg attagtcaag acagaattat tagagagcac gtaaatatca ataatattaa 6601 gttcaataaa taccctaatg taaaagatac tgatgtacct tttattgtta ttgacgatat 6661 cgacgaccca atacctacaa cttatactga cggagatgag tgtgcatata gttatattgt 6721 ccaaatagat gtttttgtta agtacaatga tgaatataat gcgagaatca taagaaataa 6781 gatatctaat cgcattcaaa agttattatg gtctgaacta aaaatgggaa atgtttcaaa 6841 tggaaaaccg gaatatatag aagaatttaa aacatataga agctctcgcg tttacgaggg 6901 cattttttat aaggaggaaa attaaatggc agtaaaacat gcaagtgcgc caaaggcgta 6961 tattaacatt actggtttag gtttcgctaa attaacgaaa gaaggcgcgg aattaaaata 7021 tagtgatatt acaaaaacaa gaggattaca aaaaattggt gttgaaactg gtggagaact 7081 aaaaacagct tatgctgatg gcggtccaat tgaatcaggg aatacagacg gagaaggtaa 7141 aatctcatta caaatgcatg cgttccctaa agagattcgc aaaattgttt ttaatgaaga 7201 ttatgatgaa gatggcgttt acgaagagaa acaaggtaaa caaaacaatt acgtagctgt 7261 atggttcaga caagagcgta aagacggtac atttagaaca gttttattac ctaaagttat 7321 gtttacaaat cctaaaatcg atggagaaac ggctgagaaa gattgggatt tctcaagtga 7381 agaggttgaa ggtgaggcac ttttcccttt agttgataat aaaaagtcag tacgtaagta 7441 tatctttgat tcagctaaca tgacaaatca tgatggagac ggtgaaaaag gcgaagaggc 7501 tttcttaaag aaaattttag gcgaagaata tactggaaac gtgacagagg gtaacgaaga 7561 aactttgtaa caaaaccggc ttcatcggaa actgcggtaa agtcggttaa tataccagat 7621 agcattaaaa cacttaaagt tggcgacaca tacgatttaa atgttgtagt agagccatct WO 00/32825 PCT/IB99/02040 143 7681 aatcaaagta agttattgaa atacacaaca gatcaaacga atattgtatc aatcaatagt 7741 gatggtcaag ttactgcgga agcacaaggc attgctacgg ttaaagcaac agttggtaat 7801 atgagtgaca ctataacaat aaatgtagaa gcataagagg gggcaacccc tctattttat 7861 ttgaaaataa ggagagtatt ataaaatggc aaaattaaaa cgtaacatta ttcaattagt 7921 agaagatcca aaagcaaatg aaattaaatt acaaacgtac ttaacaccac acttcatttc 7981 atttgaaatt gtatacgaag caatggattt aatcgatgat attgaggacg aaaatagcac 8041 gatgaagcca agagaaatcg ctgacagatt gatggatatg gttgtaaaaa tttacgataa 8101 ccaattcaca gttaaagacc taaaagaacg tatgcatgca cctgatggaa tgaatgcact 8161 tcgtgaacaa gtgattttca ttactcaagg tcaacaaact gaggaaacta gaaattttat 8221 ccagaacatg aaataaagcc tgaagattta acatataaag caatgttgaa aaatatggat 8281 actctcatga tggacttaat tgaaaatggt aaagacgcta acgaagtttt aaaaatgcca 8341 tttcattatg tgctttccat atatcaaaat aaaaataatg acatttctga agaaaaagca 8401 gaggctttaa ttgatgcatt ttaaccttaa ccgtttggtt agggttattt ttttgaactt 8461 ttttagaaag gaggtaaaaa atgggagaaa gaataaaagg tttatctata ggtttggatt 8521 tagatgcagc aaatttaaat agatcatttg cagaaatcaa acgaaacttt aaaactttaa 8581 attctgactt aaaattaaca ggcaacaact tcaaatatac cgaaaaatca actgatagtt 8641 acaaacaaag gattaaagaa cttgatggaa ctatcacagg ttataagaaa aacgttgatg 8701 atttagccaa gcaatatgac aaggtatctc aagaacaggg cgaaaacagt gcagaagctc 8761 aaaagttacg acaagaatat aacaaacaag caaatgagct gaattattta gaaagagaat 8821 tacaaaaaac atcagccgaa tttgaagagt tcaaaaaagc tcaagttgaa gctcaaagaa 8881 tggcagaaag tggctgggga aaaaccagta aagtttttga aagtatggga cctaaattaa 8941 caaaaatggg tgatggttta aaatccattg gtaaaggttt gatgattggt gtaactgcac 9001 ctgttttagg tattgcagca gcatcaggaa aagcttttgc agaagttgat aaaggtttag 9061 atactgttac tcaagcaaca ggcgcaacag gcagtgaatt aaaaaaattg cagaactcat 9121 ttaaagatgt ttatggcaat tttccagcag atgctgaaac tgttggtgga gttttaggag 9181 aagttaatac aaggttaggt tttacaggta aagaacttga aaatgccaca gagtcattct 9241 tgaaattcag tcatataaca ggttctgacg gtgtgcaagc cgtacagtta attacccgtg 9301 caatgggcga tgcaggtatc gaagcaagtg aatatcaaag tgttttggat atggtagcaa 9361 aagcggcgca agctagtggg ataagtgttg atacattagc tgatagtatt actaaatacg 9421 gcgctccaat gagagctatg ggctttgaga tgaaagaatc aattgcttta ttctctcaat 9481 gggaaaagtc aggcgttaat actgaaatag cattcagtgg tttgaaaaaa gctatatcaa 9541 attggggtaa agctggtaaa aacccaagag aagaatttaa gaagacatta gcagaaattg 9601 aaaagacgcc ggatatagct agcgcaacaa gtttagcgat tgaagcattt ggtgcaaagg 9661 caggtcctga tttagcagac gctattaaag gtggtcgctt tagttatcaa gaatttttaa 9721 aaactattga agattcccaa ggcacagtaa accaaacatt taaagattct gaaagtggct 9781 ccgaaagatt taaagtagca atgaataaat taaaattagt aggtgctgat gtatgggctt 9841 ctattgaaag tgcgtttgct cccgtaatgg aagaattaat caaaaagcta tctatagcgg 9901 ttgattggtt ttccaattta agtgatggtt ctaaaagatc aattgttatt ttcagtggta 9961 ttgctgctgc aattggtcct gtagtttttg ggttaggtgc atttataagt acaattggca 10021 atgcagtaac tgtattagct ccattgttag ctagtattgc aaaggctggt ggattgatta 10081 gttttttatc gactaaagta cctatattag gaactgtctt cacagcttta actggtccaa 10141 ttggcattgt attaggtgta ttggctggtt tagcagtcgc atttacaatt gcttataaga 10201 aatctgaaac atttagaaat tttgttaatg gtgcaattga aagtgttaaa caaacattta 10261 gtaattttat tcaatttatt caacctttcg ttgattctgt taaaaacatc tttaaacaag 10321 cgatatcagc aatagttgat ttcgcaaaag atatttggag tcaaatcaat ggattcttta 10381 atgaaaacgg aatttccatt gttcaagcac ttcaaaatat atgcaacttt attaaagcga 10441 tatttgaatt tattttaaat tttgtaatta aaccaattat gttcgcgatt tggcaagtga 10501 tgcaatttat ttggccggcg gttaaagcct tgattgtcag tacttgggag aacataaaag 10561 gtgtaataca aggtgcttta aatatcatac ttggcttgat taagttcttc tcaagtttat 10621 tcgttggtga ttggcgagga gtttgggacg ccgttgtgat gattcttaaa ggagcagttc 10681 aattaatttg gaatttagtt caattatggt ttgtaggtaa aatacttggt gttgttaggt 10741 actttggcgg gttgctaaaa ggattgatag caggaatttg ggacgtaata agaagtatat 10801 tcagtaaatc tttatcagca atttggaatg caacaaaaag tatttttgga tttttattta 10861 atagcgtaaa atcaattttc acaaatatga aaaattggtt atctaatact tggagcagta 10921 tccgtacgaa tacaatagga aaagcgcagt cattatttag tggcgtcaaa tcaaaattta 10981 ctaatttatg gaatgcgacg aaagaaattt ttagtaattt aagaaattgg atgtcaaata 11041 tttggaattc cattaaagat aatacggtag gaattgcaag ccgtttatgg agtaaggtac 11101 gtggaatttt cacaaatatg cgcgatggct tgagttccat tatagataag attaaaagtc 11161 atatcggcgg tatggtaagc gctattaaaa aaggacttaa taaattaatc gacggtttaa 11221 actgggtcgg tggtaagttg ggaatggata aaatacctaa gttacacact ggtacagagc 11281 acacacatac tactacaaga ttagttaaga acggtaagat tgcacgtgac acattcgcta 11341 cagttgggga taagggacgc ggaaatggtc caaatggttt tagaaatgaa atgattgaat 11401 tccctaacgg taaacgtgta atcacaccta atacagatac taccgcttat ttacctaaag 11461 gcicaaaagt atacaacggt gcacaaactt attcaatgtt aaacggaacg cttccaagat 11521 ttagtttagg tactatgtgg aaagatatta aatctggtgc atcatcggca tttaactgga 11581 caaaagataa aataggtaaa ggtaccaaat ggcttggcga taaagttggc gatgttttag 11641 attttatgga aaatccaggc aaacttttaa attatatact tgaagctttt ggaattgatt 11701 tcaattcttt aactaaaggt atgggaattg caggcgacat aacaaaagct gcatggtcta WO 00/32825 PCT/IB99/02040 144 11761 agattaagaa aagtgctact gattggataa aagaaaattt agaagctatg ggcggtggcg 11821 atttagtcgg cggaatatta gaccctgaca aaattaatta tcattatgga cgtaccgcag 11881 cttataccgc tgcaactgga agaccatttc atgaaggtgt cgattttcca tttgtatatc 11941 aagaagttag aacgccgatg ggtggcagac ttacaagaat gccatttatg tctggtggtt 12001 atggtaatta tgtaaaaatt actagtggcg ttatcgatat gctatttgcg catttgaaaa 12061 actttagcaa atcaccacct agtggcacga tggtaaagcc cggtgatgtt gttggtttaa 12121 ctggtaatac cggatttagt acaggaccac atttacattt tgaaatgagg agaaatggac 12181 gacattttga ccctgaacca tatttaagga atgctaagaa aaaaggaaga ttatcaatag 12241 gtggtggcgg tgctacttct ggaagtggcg caacttatgc cagtcgagta atccgacaag 12301 cgcaaagtat tttaggtggt cgttataaag gtaaatggat tcatgaccaa atgatgcgcg 12361 ttgcaaaacg tgaaagtaac taccagtcaa atgcagtgaa taactgggat ataaatgctc 12421 aaagaggaga cccatcaaga ggattattcc aaatcatcgg ctcaactttt agagcaaacg 12481 ctaaacgtgg atatactaac tttaataatc cagtacatca aggtatctca gcaatgcagt 12541 acattgttag acgatatggt tggggtggtt ttaaacgtgc tggtgattac gcatatgcta 12601 caggtggaaa agtttttgat ggttggtata acttaggtga agacggtcat ccagaatgga 12661 ttattccaac agatccagct cgtagaaatg atgcaatgaa gattttgcat tatgcagcag 12721 cagaagtaag agggaaaaaa gcgagtaaaa ataagcgtcc tagccaatta tcagacttaa 12781 acgggtttga tgatcctagc ttattattga aaatgattga acaacagcaa caacaaatag 12841 ctttattact gaaaatagca caatctaacg atgtgattgc agataaagat tatcagccga 12901 ttattgacga atacgctttt gataaaaagg tgaacgcgtc tatagaaaag cgagaaaggc 12961 aagaatcaac aaaagtaaag tttagaaaag gaggaattgc tattcaatga tagacactat 13021 taaagtgaac aacaaaacaa ttccttggtt gtatgtcgaa agagggtttg aaataccctc 13081 ttttaattat gttttaaaaa cagaaaatgt agatggacgt tcggggtcta tatataaagg 13141 gcgtaggctt gaatcttata gttttgatat acctttggtg gtacgtaatg actatttatc 13201 tcacaacggc attaaaacac atgatgacgt cttgaatgaa ttagtaaagt tttttaacta 13261 cgaggaacaa gttaaattac aattcaaatc taaagattgg tactggaacg cttatttcga 13321 aggaccaata aagctgcaca aagaatttac aatacctgtt aagttcacta tcaaagtagt 13381 actaacagac ccttacaaat attcagtaac aggaaataaa aatactgcga tttcagacca 13441 agtttcagtt gtaaatagtg ggactgctga cactccttta attgttgaag cccgagcaat 13501 taaaccatct agttacttta tgattactaa aaatgatgaa gattatttta tggttggtga 13561 tgatgaggta accaaagaag ttaaggatta catgcctcct gtttatcata gtgagtttcg 13621 tgatttcaaa ggttggacta agatgattac tgaagatatt ccaagtaatg acttaggtgg 13681 taaggtcggc ggtgactttg tgatatccaa tcttggcgaa ggatataaag caactaattt 13741 tcctgatgca aaaggttggg ttggtgctgg cacgaaacga gggctcccta aagcgatgac 13801 agattttcaa attacctata aatgtattgt tgaacaaaaa ggtaaaggtg ccggaagaac 13861 agcacaacat atttatgata gtgatggtaa gttacttgct tctattggtt atgaaaataa 13921 atatcatgat agaaaaatag gacatattgt tgttacgttg tataaccaaa aaggagaccc 13981 caaaaagata tacgactatc agaataaacc gataatgtat aacttggaca gaatcgttgt 14041 ttatatgcgg ctcagaagag taggtaataa attttctatt aaaacttgga aatttgatca 14101 cattaaagac ccagatagac gtaaacctat tgatatggat gagaaagagt ggatagatgg 14161 cggtaagttt tatcagcgtc cagcttctat catagctgtc tatagtgcga agtataacgg 14221 ttataagtgg atggagatga atgggttagg ttcattcaat acggagattc taccgaaacc 14281 gaaaggcgca agggatgtca ttatacaaaa aggtgattta gtaaaaatag atatgcaagc 14341 aaaaagtgtt gtcatcaatg aggaaccaat gttgagcgag aaatcgtttg gaagtaatta 14401 tttcaatgtt gattctgggt acagtgaatt aatcatacaa cctgaaaacg tctttgatac 14461 gacggttaaa tggcaagata gatatttata gaaaggagat gagagtgtga tacatgtttt 14521 agattttaac gacaagatta tagatttcct ttctactgat gacccttcct tagttagagc 14581 gattcataaa cgtaatgtta atgacaattc agaaatgctt gaactgctca tatcatcaga 14641 aagagctgaa aagttccgtg aacgacatcg tgttattata agggattcaa acaaacaatg 14701 gcgtgaattt attattaact gggttcaaga tacgatggac ggctacacag agatagaatg 14761 tatagcgtct tatcttgctg atataacaac agctaaaccg tatgcaccag gcaaatttga 14821 gaaaaagaca acttcagaag cattgaaaga tgtgttgagc gatacaggtt gggaagtttc 14881 tgaacaaacc gaatacgatg gcttacgtac tacgtcatgg acttcttatc aaactagata 14941 tgaagtttta aagcaattat gtacaaccta taaaatggtt ttagattttt atattgagct 15001 tagctctaat accgtcaaag gtagatatgt agtactcaaa aagaaaaaca gcttattcaa 15061 aggtaaagaa attgaatatg gtaaagattt agtcgggtta actaggaaga ttgatatgtc 15121 agaaatcaaa acagcattaa ttgctgtggg acctgaaaat gacaaaggga agcgtttaga 15181 gctagttgtg acagatgacg aagcgcaaag tcaattcaac ctacctatgc gctatatttg 15241 ggggatatat gaaccacaat cagatgatca aaatatgaat gaaacacgat taagttcttt 15301 agccaaaaca gagttaaata aacgtaagtc ggcagttatg tcatatgaga ttacttctac 15361 tgatttggaa gttacgtatc cgcacgagat tatatcaatt ggcgatacag tcagagtaaa 15421 acatagagat tttaacccgc cattgtatgt agaggcagaa gttattgctg aagaatataa 15481 cataatttca gaaaatagca catatacatt cggtcaacct aaagagttca aagaatcaga 15541 attacgagaa gagtttaaca agcgattgaa cataatacat caaaagttaa acgataatat 15601 tagcaatatc aacactatag ttaaagatgt tgtagatggt gaattagaat actttgaacg 15661 caaaatacac aaaagtgata caccgccaga aaatccagtc aatgatatgc tttggtatga 15721 tacaagtaac cctgatgttg ctgtcttgcg tagatattgg aatggtcgat ggattgaagc 15781 aacaccaaat gatgttgaaa aattaggtgg tataacaaga gagaaagcgc tattcagtga WO 00/32825 PCT/IB99/02040 145 15841 attaaacaat atttttatta atttatctat acaacacgct agtcttttgt cagaagctac 15901 agaattactg aatagcgagt acttagtaga taatgatttg aaagcggact tacaagcaag 15961 tttagacgct gtgattgatg tttataatca aattaaaaat aatttagaat ctatgacacc 16021 cgaaactgca acgattggtc ggttggtaga tacacaagct ttatttcttg agtatagaaa 16081 gaaattacaa gatgtttata cagatgtaga agatgtcaaa atcgccattt cagatagatt 16141 taaattatta cagtcacaat acactgatga aaaatataaa gaagcgttgg aaataatagc 16201 aacaaaattt ggtttaacgg tgaatgaaga tttgcagtta gtcggagaac ctaatgttgt 16261 taaatcagct attgaagcag ctagagaatc cacaaaagaa caattacgtg actatgtaaa 16321 aacatcggac tataaaacag acaaagacgg tattgttgaa cgtttagata ctgctgaagc 16381 tgagagaacg actttaaaag gtgaaatcaa agataaagtt acgttaaacg aatatcgaaa 16441 cggattggaa gaacaaaaac aatatactga tgaccagtta agtgatttgt ccaataatcc 16501 tgagattaaa gcaagtattg aacaagcaaa tcaagaagcg caagaagctt taaaatcata 16561 cattgatgct caagatgatc ttaaagagaa ggaatcgcaa gcgtatgctg atggtaaaat 16621 ttcggaagaa gagcaacgcg ctatacaaga tgctcaagct aaacttgaag aggcaaaaca 16681 aaacgcagaa ctaaaggcta gaaacgctga aaagaaagct aatgcttata cagacaacaa 16741 ggtcaaagaa agcacagatg cacagaggaa aacattgact cgctatggtt ctcaaattat 16801 acaaaatggt aaggaaatca aattaagaac tactaaagaa gagtttaatg caaccaatcg 16861 tacactttca aatatattaa acgagattgt tcaaaatgtt acagatggaa caacaatcag 16921 atatgatgat aacggagtgg ctcaagcttt gaatgtgggg ccacgtggta ttagattaaa 16981 tgctgataaa attgatatta acggtaatag agaaataaac cttcttatcc aaaatatgcg 17041 agataaagta gataaaaccg atattgtcaa cagtcttaat ttatcaagag agggtcttga 17101 tatcaatgtt aatagaattg gaattaaagg cggtgacaat aacagatatg ttcaaataca 17161 gaatgattct attgaactag gtggtattgt gcaacgtact tggagaggga aacgttcaac 17221 agacgatatt tttacgcgac tgaaagacgg tcacctaaga tttagaaata acaccgctgg 17281 cggttcactt tatatgtcac attttggtat ttcgacttat attgatggtg aaggtgaaga 17341 cggtggttca tctggtacga ttcaatggtg ggataaaact tacagtgata gtggcatgaa 17401 tggtataaca atcaattcct atggtggtgt cgttgcacta acgtcagata ataatcgggt 17461 tgttctggag tcttacgctt catcgaatat caaaagcaaa caggcaccgg tgtatttata 17521 tccaaacaca gacaaagtgc ctggattaaa ccgatttgca ttcacgctgt ctaatgcaga 17581 taatgcttat tcgagtgacg gttatattat gtttggttct gatgagaact atgattacgg 17641 tgcgggtatc aggttttcta aagaaagaaa taaaggtctt gttcaaattg ttaatggacg 17701 atatgcaaca ggtggagata caacaatcga agcagggtat ggcaaattta atatgctgaa 17761 acgacgtgat ggtaataggt atattcatat acagagtaca gacctactgt ctgtaggttc 17821 agatgatgca ggagatagga tagcttctaa ctcaatttat agacgtactt attcggccgc 17881 agctaatttg catattactt ctgctggcac aattgggcgt tcgacatcag cgcgtaaata 17941 caagttatct atcgaaaatc aatataacga tagagatgaa caactggaac attcaaaagc 18001 tattcttaac ttacctatta gaacgtggtt tgataaagct gagtctgaaa ttttagctag 18061 agagctgaga gaagatagaa aattatcgga agacacctat aaacttgata gatacgtagg 18121 tttgattgct gaagaggtgg agaatttagg attaaaagag tttgtcacgt atgatgacaa 18181 aggagaaatt gaaggtatag cgtatgatcg tctatggatt catcttatcc ctgttatcaa 18241 agaacaacaa ctaagaatca agaaattgga ggagtcaaag aatgcaggat aacaaacaag 18301 gattacaagc taatcctgaa tatacaattc attatttatc acaggaaatt atgaggttaa 18361 cacaagaaaa cgcgatgtta aaagcgtata tacaagaaaa taaagaaaat caacaatgtg 18421 ctgaggaaga gtaatcctta gcactatttt tatacaaaaa tttaaggagg tcatttaatt 18481 atggcaaaag aaattatcaa caatacagaa aggtttattt tagtacaaat cgacaaagaa 18541 ggtacagaac gtgtagtata tcaagatttc acaggaagtt ttacaacttc tgaaatggtt 18601 aaccatgctc aagattttaa atctgaagaa aacgctaaga aaattgcgga gacgttaaat 18661 ttgttatatc aattaactaa caaaaaacaa cgtgtgaaag tagttaaaga agtagttgaa 18721 agatcagatt tatctccaga ggtaacagtt aacactgaaa cagtatgaaa agctatgagt 18781 tagatactca tagtctttat tcttttagaa agcgggtgta ctgaattggg gtggttcaaa 18841 aaacacgaac atgaatggcg catcagaagg ttagaagaga atgataaaac aatgctcagc 18901 acactcaacg aaattaaatt aggtcaaaaa acccaagagc aagttaacat taaattagat 18961 aaaaccttag atgctattca aaaagaaaga gaaatagatg aaaagaataa gaaagaaaat 19021 gataagaaca tacgtgatat gaaaatgtgg gtgcttggtt tagttgggac aatatttggg 19081 tcgctaatta tagcattatt gcgtatgctt atgggcatat aagagaggtg attaccatgt 19141 tcggattaaa ttttggagct tcgctgtgga cgtgtttctg gtttggtaag tgtaagtaat 19201 agttaagagt cagtgcttcg gcactggctt tttattttgg ataaaaggag caaacaaatg 19261 gatgcaaaag taataacaag atacatcgta ttgatcttag cattagtaaa tcaattctta 19321 gcgaacaaag gtattagccc aattccagta gacgatgaaa ctatatcatc aataatactt 19381 actgtagtcg ctttatatac aacgtataaa gacaatccaa catctcaaga aggtaaatgg 19441 gcaaatcaaa aattaaagaa atataaagct gaaaataagt atagaaaagc aacagggcaa 19501 gcgccaatta aagaagtaat gacacctacg aatatgaacg acacaaatga tttagggtag 19561 gtggttgata tatgttaatg acaaaaaatc aagcagaaaa atggtttgac aattcattag 19621 ggaaacaatt caacccagat ggttggtatg gatttcagtg ttatgattac gccaatatgt 19681 tctttatgtt agcgacaggc gaaaggctgc aaggtttata tgcttataat atcccgtttg 19741 ataataaagc aaagattgaa aaatatggtc aaataattaa aaactatgac agctttttac 19801 cgcaaaagtt ggatattgtc gttttcccgt caaagtatgg tggcggagct ggacacgttg 19861 aaattgttga gagcgcaaat ttaaatactt tcacatcatt tggtcaaaac tggaacggta WO 00/32825 PCT/IB99/02040 146 19921 aaggttggac taatggcgtt gcgcaacctg gttggggtcc tgaaactgtg acaagacatg 19981 ttcattatta tgacaatcca atgtatttta ttaggttaaa cttccctaac aacttaagcg 20041 ttggcaataa agctaaaggt attattaagc aagcgactac aaaaaaagag gcagtaatta 20101 aacctaaaaa aattatgctt gtagccggtc atggttataa cgatcctgga gcagtaggaa 20161 acggaacaaa cgaacgcgat tttatacgta aatatataac gcctaatatc gctaagtatt 20221 taagacatgc aggacatgaa gttgcattat acggtggctc aagtcaatca caagatatgt 20281 atcaagatac tgcatacggt gttaatgtag gcaataaaaa agattatggc ttatattggg 20341 ttaaatcaca ggggtatgac attgttctag aaatacattt agacgcagca ggagaaagcg 20401 caagtggtgg gcatgttatt atctcaagtc aattcaatgc agatactatt gataaaagta 20461 tacaagatgt tattaaaaat aacttaggac aaataagagg tgtgacacct cgtaatgatt 20521 tactaaatgt taatgtatca gcagaaataa atataaatta tcgtttatct gaattaggtt 20581 ttattactaa taaaaatgat atggattgga ttaagaaaaa ctatgacttg tattctaaat 20641 taatagccgg tgcgattcat ggtaagccta taggtggttt ggtagctggt aatgttaaaa 20701 catcagctaa aaacaaaaaa aatccaccag tgccagcagg ttatacactc gataagaata 20761 atgtccctta taaaaaagaa caaggcaatt acacagtagc taatgttaaa ggtaataatg 20821 taagagacgg ttattcaact aattcaagaa ttacaggggt attacccaac aacacaacaa 20881 ttacgtatga cggtgcatat tgtattaatg gttatagatg gattacttat attgctaata 20941 gtggacaacg tcgttatata gcgacaggag aggtagacaa ggcaggtaat agaataagta 21001 gttttggtaa gtttagcacg atttagtatt tacttagaat aaaaattttg ctacattaat 21061 tatagggaat cttacagtta ttaaataact atttggatgg atgttaatat tcctatacac 21121 tttttaacat ttctctcaag atttaaatgt agataacagg caggtacttc ggtacttgcc 21181 tattttttta tgttatagct agccttcggg ctagtttttt gttatgatgt gttacacatg 21241 catcaactat ttacatctat ccttgttcac ccaagcatgt cactggatgt tttttcttgc 21301 gatagagagc atagttttca tactactccc cgtagtatat atgactttag cattcccgta 21361 taacagttta cggggtgctt ttatgttata attgctttta tatagtagga gtgaactata 21421 tagccgggca gaggccatgt atctgactgt tggtcccaca ggagacatct tccttgtcat 21481 cactcgatac atatatctta acaacataga aatgttacat tcgctataac cgtatcttaa 21541 tcgatacggt tatatttatt cccctacaac caacaaaacc acagatccta ttaatttagg 21601 attgtggtta ttttttgcgt ttttttgggg caaaaaaagg gcagattatt tgaaaaaggg 21661 caaacgcttg tggaaaagct aaaaggttaa aaatgacaaa aaccttgata caacagtgtt 21721 tttggacgct cgtgtacgtt agagaatgac cggtttacca tcatacaagg gtgggattaa 21781 cttgtgttaa aaagccttta atatcagttg ttacaaagga tttgtagcgt ctttaaaaat 21841 aaaaaagggc agaaaaaggg cagatacctt ttagtacaca agtttttcta atttttgctc 21901 taactctctg tccattttct ctgttacatg tgtatacacc tttatagtcg ttttttcatc 21961 tgtatgtcct actcttttca taattgcttt taacgatata ttcatttccg ccaataaact 22021 tatgtgtgta tgccttagtg tgtgagtagt aactttttta tttatattta atgattctgc 22081 agctgaggac aatcgtttgt ttatcctact gccttgcata ggatttcctt ggcaagttgt 22141 gaatataaac cctctatcaa catagcttgg ttcccattgt tgcatctttt tattttctaa 22201 cattattttt ttcaatacat ttgctatcct tgaattgatg gcgatttttc ttcttgaacc 22261 tgcggtctta gtagtatctt tgtgaccaaa tccagcatta catttgattc tgtgaatagt 22321 gccattaata gcgatcgttt tatttttgag gtcaacatct ttaacttgga gagctaataa 22381 ctcacctatg cgcatacctg ttaaagcttg aacttctaca gccccagcaa ctaaaatacg 22441 agctctatac tgcatgttat tatcgttcag tataaaatcg cgtatctgta ttacctgttc 22501 catctctaaa tagttataca ttttcgcttc ttctttttct atatcttcta tcgtcttact 22561 cttctttggt agtgtgacgc tatttaatat gtgttcgttt ggataattgt aaaatttaac 22621 ggcgtattta atagcttctt tcatatgtcc aagttgacgc tttacctgat ttgcagaata 22681 tacgtttgat aatttgttaa taaatgtttg catgtacttt gtatcaattt tgtttaaaag 22741 taaattttga gaactgttct ttttgatgtt tttgattctt gttttcaaat tatcaagcgt 22801 cgttacttta aagccagatg tttttatatg atattcaagc cattcatcta ataacgcgtg 22861 aaaagtcaaa gtttttaatt cgcttgacga cttgttgttt agtttttctt ttattttttc 22921 ttctaaacga aacattgcct ctttttgcga ttgctttgta ttcttattca agacaacact 22981 tacacgtttc catttatctg tatacggatc tttgtatttc tcgtagtatc tatacttcgt 23041 ttcattgttc ttatttttaa atttttcaaa ccacatttta catccctcct caaaattggc 23101 aaaaaataat aagggtaggc gggctaccca tgaaaattgt ataaaaaaag acgcctgtat 23161 aaaatacaga cgccacttat aattataaga ttacatggtt aattaccaaa aatggtaacg 23221 aatatatacg tgttttaaag gataaacctt taatatatta aaattatatc atcttatatc 23281 agggatctgc aatatattat tattaattct atttatcagt aacataatat ccgaagaatc 23341 tattactgga tttttaattt tttggggtaa aacttttctt atgcgaaact tactaatcgg 23401 ctggaaagaa tttatgcaag cgtaactatt accttttaat ttttttacct tatcaattgc 23461 tgatactatg ttattaatgt ttctgtcaat tttatttaat ttattttcaa tttctaaact 23521 atcagatata aattcaataa aataatcttt agtgatgaat tctgtgttgt ttttttggta 23581 ttttttatcg aaaacttctt ttaatatagc tgaattattt tgcgcgctaa ttaaatttaa 23641 aaacaatctt aaataatact cccatttcaa atcaaaattc atctttaaat actttttgtt 23701 ttctttagag gataagggaa taacatttac tatatcctcc gtattagaat catttttatt 23761 catcactatt gcaaagtgtg aattagaaaa ttctttatta acgtttatac cgaaatctac 23821 aaaaactatt tctccttgtt taaactttgg ataaaaacct ttatggtttt tttcaccttc 23881 aaatctcttg agtaaatagt gaatatctga atctaacttt ttaaattttg gatttccaga 23941 agtttttaat ttattaatgc gtttttctat attatgcgtc atcatttctc ctttattctc WO 00/32825 PCT/IB99/02040 147 24001 gctcacactc tcaccaccat tcaacgtcta cacttgtagg cgttttttga ttagtaaaat 24061 cataatgaat cttctttggt taacttatcg ccatctattt tttgtgaaat aaattccaag 24121 tatttacgcg cattatgtga cgataaatct ttaggtaact cataagtgaa tggttgatta 24181 ccactagtta aaacttcata tactatagtt tcttttttta ttttgcaatt agttattttc 24241 attataaact ccttttaaac actgctgaaa tagacgtctt tttcaaataa gcatgattaa 24301 tactttaatt ctttaatcca catatattta aaagtgaggt agtaggtaat aaatataaga 24361 cttaaagtta agattgcttt tttcatgtca atttctcctt tgtttatatt tatattaaag 24421 cgctaaatat acgttattaa tcacaataca actttgccca ttactttaat atcactaaac 24481 gaagcgactt tgatatcatc atacttcgga tttagagata ccaaattaat atagtcttcg 24541 catatatcta cacgcttgat aagacttact ccatctaata caacgagtgc aattgtacca 24601 tctttaatag aatcttcttt cttaataaaa gcgtatgttc cttgttttaa cataggttcc 24661 attgaatcac cattaactaa aatacaaaaa tcagcatttg atggcgtttc gtcttcttta 24721 aaaaatactt cttcatgcaa tatgtcatca tataattctt ctcctatgcc agcaccagtt 24781 gcaccacatg caatatacga tactagttta gactctttat attcatctat agaagtgact 24841 ttattctgtt catctaattg ctcatttgca tagttaagta cgttttcttg gcggggaggt 24901 gtgagttgag aaaatatgtt attgattttt gacattatcg tttcatcttg acgttcttcg 24961 tcaggaactc gataagaatc tacatcatac cccataagcc acgcttcacc gacatttaaa 25021 gttttagata ataagaataa tttatgttgg tctggagaag accttccatt aacatactgg 25081 gataagtgac tttttgacat tttaatattc aattcttttt gaaagggttt cgacttttct 25141 agaatatcta cttgacgcaa gttcctatct ttcataattt gttttaatct ttcagaagtg 25201 ttttgcattg gtaatgcctc cttgaaattc attatatagg aagggaaata aaaatcaata 25261 caaaagttca acttttttaa ctttttgtgt tgacattgtt caaaattggg gttatagtta 25321 ttatagttca aatgtttgaa cttaggaggt gattatttga atactaatac aacttttgat 25381 ttttcgttat tgaacggtaa gatagtcgaa gtgtactcga cacaatttaa ctttgctata 25441 gctttaggtg tatcagaaag aactttgtct ttgaagttga acaacaaagt accatggaaa 25501 acaacagaca ttattaaagc ttgtaagtta ttgggaatac ctataaaaga tgttcacaaa 25561 tattttttta aacagaaagt tcaaatgttt gaacttaata agtaaaggag gcataacaca 25621 tgcaagaacg agaaaaggtt aataaaagta acacatcttc aaatgaagca tcaaaacctt 25681 ttaggacaaa ttgaagctta cgacaaaacg cttaaagaaa taaagtacac tcgagacctt 25741 tacaacaaac acctaagcat gaacaacgaa gacgcattcg ctggtttgga aatggtagag 25801 gatgaaatta ctaaaaagct acgaagtgct atcaaagagt tccaaaaagt agtgaaagcg 25861 ttagacaagc ttaacggtgt tgaaagcgat aacaaagtta ctgatttaac agagtggcgg 25921 aaagtgaatc agtaacattc acttcttaat ataaccacgc ttatcaacat ccacattgag 25981 cagatgtgag cgagagctgg cgatgatatg agccgcgttt aaatacattc gatagtcatt 26041 gcgataaccg tctgctgaat gtgggtgttg aggaaaaagg aggatactca aatgcaagca 26101 ttacaaacat ttaattttaa agagctacca gtaagaacag tagaaattga aaacgaacct 26161 tattttgtag gaaaagatat tgctgagatt ttaggatatg caagatcaaa caatgccatt 26221 agaaatcatg ttgatagcga ggacaagctg acgcaccaat ttagtgcatc aggtcaaaac 26281 agaaatatga tcattatcaa cgaatcagga ttatacagtc taatcttcga tgcttctaaa 26341 caaagcaaaa acgaaaaaat tagagaaacc gctagaaaat tcaaacgctg ggtaacatca 26401 gatgtcctac cagctattcg caaacacggt atatacgcaa cagacaatgt aattgaacaa 26461 acattaaaag atccagacta catcattaca gtgttgactg agtataagaa agaaaaagag 26521 caaaacttac ttttacaaca gcaagtagaa gttaacaaac caaaagtatt attcgctgac 26581 tcggtagctg gtagtgataa ttcaatactt gttggagaac tagcgaaaat acttaaacaa 26641 aacggtgttg atataggaca aaacagattg ttcaaatggt taagaaataa tggatatctc 26701 attaaaaaga gtggagaaag ttataactta ccaactcaaa agagtatgga tctaaaaatc 26761 ttggatatca aaaaacgaat aattaataat ccagatggtt caagtaaagt atcacgtaca 26821 ccaaaagtaa caggcaaagg acaacaatac tttgttaata agtttttagg agaaaaacaa 26881 acatcttaaa aggaggaaca caatggaaca aatcacatta accaaagaag agttgaaaga 26941 aattatagca aaagaagtta gagaggctat aaatggcaag aaaccaatca gttcaggttc 27001 aattttcagt aaagtaagaa tcaataatga cgatttagaa gaaatcaata aaaaactcaa 27061 tttcgcaaaa gatttgtcgc taggaagatt gaggaagctc aatcatccga ttccgctaaa 27121 aaagtatcag catggcttcg aatcaattca tcaaaaagct tatgtacaag atgttcatga 27181 ccatattaga aaattaacat tatcaatttt tggagtgaca cttaattcag acttgagtga 27241 aagtgaatac aacctagcag caaaagttta tcgagaaatc aaaaactatt atttatacat 27301 ctatgaaaag agagtttcag aattaactat cgatgatttc gaataaagga ggaacaacaa 27361 atgttacaaa aatttagaat tgcgaaagaa aaaaataaat taaaactcaa attactcaag 27421 catgctagtt actgtttaga aagaaacaac aaccctgaac tgttgcgagc agttgcagag 27481 ttgttgaaaa aggttagcta aattcaacgg taaggatttg ccctgcctcc acacttagag 27541 tttgagatcc aacaaacaca taagttttag tagggtctag aaaaaatgtt tcgatttcct 27601 cttttgtaac agtttcaatt ccttcatatc ctggaaaaac aattttcttt aaatccgaaa 27661 catgtttttt tgaaccatcc tttaaagtaa ctagaagttt catacttatc acctccttag 27721 gttgataaca acattataca cgaaaggagc ataaacaata tgcaagcatt acaaacaaat 27781 tcgaacatcg gagaaatgtt caatattcaa gaaaaagaaa atggagaaat cgcaatcagc 27841 ggtcgagaac ttcatcaagc attagaagtt aagacagcat ataaagattg gtttccaaga 27901 atgcttaaat acggatttga agaaaataca gattacacag ctatcgctca aaaaagagca 27961 acagctcaag gcaatatgac tcactatatt gaccacgcac tcacactaga cactgcaaaa 28021 gaaatcgcaa tgattcaacg tagtgaacct ggcaaacgtg caagacaata tttcatccaa WO 00/32825 PCT/IB99/02040 148 28081 gttgaaaaag catggaacag cccagaaatg attatgcaac gtgctttaaa aattgctaac 28141 aacacaatca atcaattaga aacaaagatt gcacgtgaca aaccaaaaat tgtatttgca 28201 gatgcagtag ctactactaa gacatcaatt ttagttggag agttagcaaa gatcattaaa 28261 caaaacggta taaacatcgg gcaacgcaga ttgtttgagt ggttacgtca aaacggattc 28321 cttattaaac gcaagggtgt ggattataac atgcctacac agtattcaat ggaacgtgag 28381 ttattcgaaa ttaaagaaac atcaatcaca cattcggacg gtcacacatc aattagtaag 28441 acgccaaaag taacaggtaa aggacaacaa tactttgtta acaagttttt aggagaaaaa 28501 caaacaactt aataggagga attacaaatg aacgcactat acaaaacaac cctcctcatc 28561 acaatggcag ttgtgacgtg gaaggtttgg aagattgaga agcacactag aaaacctgtg 28621 attagtagca gggcgttgag tgactatcta aacaacaaat ctttaaccat accgaaagat 28681 gctgaaaatt ctactgaatc tgctcgtcgc cttttgaagt tcgccgaaca aactattagc 28741 aaataacaac attatacacg aaaggaaaga tagaaatgcc aaaaatcata gtaccaccaa 28801 caccagaaaa cacatataga ggcgaagaaa aatttgtgaa aaagttatac gcaacaccta 28861 cacaaatcca tcaattgttt ggagtatgta gaagtacagt atacaactgg ttgaaatatt 28921 accgcaaaga taatttaggt gtagaaaatt tatacattga ttattcacca acaggcactc 28981 tgattaatat ttctaaattg gaagagtatt tgatcagaaa gcataaaaaa tggtattagg 29041 aggatattaa atgagcaaca tttataaaag ctacctagta gcagtattat gcttcacagt 29101 cttagcgatt gtacttatgc cgtttctata cttcactaca gcatggtcaa ttgcgggatt 29161 cgcaagtatc gcaacattca tgtactacaa agaatgcttt ttcaaagaat aaaaaaactg 29221 ctacttgttg gagcaagtaa cagtatcaaa cacttaagaa aaaattcatg ttcaatataa 29281 aacgaaaaac ggaggaagtc aagatgtatt acgaaatagg cgaaatcata cgcaaaaata 29341 ttcatgttaa cggattcgat tttaagctat tcattttaaa aggtcatatg ggcatatcaa 29401 tacaagttaa agatatgaac aacgtaccaa ttaaacatgc ttatgtcgta gatgagaatg 29461 acttagatat ggcatcagac ttatttaacc aagcaataga tgaatggatt gaagagaaca 29521 cagacgaaca ggacagacta attaacttag tcatgaaatg gtaggaggtc gctatgaagc 29581 agactgtaac ttatatcatt cgtcataggg atatgccaat ttatataact aacaaaccaa 29641 ctgataacaa ttcagatatt agttactcca caaatagaaa tagagctagg gagtttaacg 29701 gtatggaaga agcgagtatc aatatggatt atcacaaagc aatcaagaaa acagtgacag 29761 aaactattga gtacgaggag gtagaacatg actgaggaaa aacaagaacc acaagaaaaa 29821 gtaagcatac tcaaaaaact aaagataaat aatatcgctg agaaaaataa aaggaaattc 29881 tataaatttg cagtatacgg aaaaattggc tcaggaaaaa ccacgtttgc tacaagagat 29941 aaagacgctt tcgtcattga cattaacgaa ggtggaacaa cggttactga cgaaggatca 30001 gacgtagaaa tcgagaacta tcaacacttt gtttatgttg taaatttttt acctcaaatt 30061 ttacaggaga tgagagaaaa cggacaagaa atcaatgttg tagttattga aactattcaa 30121 aaacttagag atatgacatt gaatgatgtg atgaaaaata agtctaaaaa accaacgttt 30181 aatgattggg gagaagttgc tgaacgaatt gtcagtatgt acagattaat aggaaaactt 30241 caagaagaat acaaattcca ctttgttatt acaggtcatg aaggtatcaa caaagataaa 30301 gatgatgaag gtagcactat caaccctact atcactattg aagcgcaaga acaaattaaa 30361 aaagctatta cttctcaaag tgatgtgtta gctagggcaa tgattgaaga atttgatgat 30421 aacggagaaa agaaagctag atatattcta aacgctgaac cttctaatac gtttgaaaca 30481 aagattagac attcaccttc aataacaatt aacaataaga aatttgcaaa tcctagcatt 30541 acggacgtag tagaagcaat tagaaatgga aactaaaaat taattaaaag gacggtattt 30601 aattatgaaa atcacaggac aagcgcaatt tactaaagaa acaaatcaag aaaagtttta 30661 taacggctca gcagggtttc aagctggaga attcacagtg aaagttaaaa atattgaatt 30721 caatgataga gaaaatagat atttcacaat cgtatttgaa aatgatgaag gcaaacaata 30781 taaacataat caatttgtac cgccgtataa atatgatttc caagaaaaac aattgattga 30841 attagttact cgattaggta ttaagttaaa tcttcctagc ttagattttg ataccaatga 30901 tcttattggt aagttttgtc acttggtatt gaaatggaaa ttcaatgaag atgaaggtaa 30961 gtattttacg gatttttcat ttattaaacc ttacaaaaag ggcgatgatg ttgttaacaa 31021 acctattccg aagacagata agcaaaaagc tgaagaaaat aacggggcac aacaacaaac 31081 atcaatgtct caacaaagca atccatttga aagcagtggc caatttggat atgacgacca 31141 agatttagcg ttttaaggtg tggtttaaat gcaatacatt acaagatacc agaaagataa 31201 cgacggtact tattccgtcg ttgctactgg tgttgaactt gaacaaagtc acattgactt 31261 actagaaaac ggatatccac taaaagcaga agtagaggtt ccggacaata aaaaactatc 31321 tatagaacaa cgcaaaaaaa tattcgcaat gtgtagagat atagaacttc actggggcga 31381 accagtagaa tcaactagaa aattattaca aacagaattg gaaattatga aaggttatga 31441 agaaatcagt ctgcgcgact gttctatgaa agttgcaagg gagttaatag aactgattat 31501 agcgtttatg tttcatcatc aaatacctat gagtgtagaa acgagtaagt tgttaagcga 31561 agataaagcg ttattatatt gggctacaat caaccgcaac tgtgtaatat gcggaaagcc 31621 tcacgcagac ctggcacatt atgaagcagt cggcagaggc atgaacagaa acaaaatgaa 31681 ccactatgac aaacatgtat tagcgttatg tcgcgaacat cacaacgagc aacatgcgat 31741 tggcgttaag tcgtttgatg ataaatacca cttgcatgac tcgtggataa aagttgatga 31801 gaggctcaat aaaatgttga aaggagagaa aaaggaatga atagactaag aataataaaa 31861 atagcactcc taatcgtcat cttggcggaa gagattagaa atgctatgca tgctgtaaaa 31921 gtggagaaaa ttttaaaatc tccgtttagt taatacaggt ttttacaaaa gctttaccat 31981 aggcggacaa actaattgag ccttttttga tgtctattac ccaggggctg taatgtaact 32041 ttaatacttc aaattcaatg ccagaaagtt tacttattgt ttctaggttg tgtcctgact 32101 ttaacattct tttaacaaat tctaatcccg aaacaaatct ttgtttttct ataatcttat WO 00/32825 PCT/IB99/02040 149 32161 taaagtgatt taaaaactga ggagcataaa acttattata aattcctttt tttgttaagt 32221 aagacatgtc aaaagtttca tttaaaaccc ctaaccttac taggttatta attgaaattt 32281 cggttgattc tatatctaac ggagagtctt ttattaacgt gtccgatata ttcataccgt 32341 cattctttgg gtttaaaacc gctctatatt taacggcagg atgtacttcg tgattcttta 32401 aatgttttaa aagaatagca tcatttgggg ataattgttt aattatttca acaaatgaat 32461 ggtgggttaa tgagtttttt ctgtcatcca tagatgatgc tattagtttt gcgaacatat 32521 tacttaaagt tttttcacta atgtaaaact ttgaagcttc tagagcagga cctagaagag 32581 aaaattgtgg ttcttgtaaa ttatttttag gtacagaaga tatttctttt ttaaattgtt 32641 ctttgaattt ttcaaattct acttctcttt gataaataac tttatccaca taaaggtgga 32701 atttcccaaa gacaagttcc caagttttag agaatgtttc tacaggccct tttgatgcgc 32761 cttcaataat tttatcaata cctttaccta aaataggatc cataattatt cacccccaat 32821 ctaacgcaat agcgataata aaattatacc agaaaggaga atcaacatga ctgaccaacc 32881 aagttactac tcaataatta cagcaaatgt cagatacgat aaccgactta ctgacagcga 32941 aaagttactt tttgcagaaa taacatcttt aagtaacaaa tacggatact gcacagcaag 33001 taatggttac tttgcaactt tatacaacgt tgttaaggaa actatatctc gtagaatttc 33061 gaaccttacc aactttggtt atctaaaaat cgaaattatc aaagaaggta atgaagttaa 33121 acaaaggaag atgtacccct tgacgcaaac gtcaatacct attgacgcaa aaatcaatac 33181 ccctattgat aattctgtca atacccctat tgacgcaaat gtcaaagaga atattacaag 33241 tattaataat acaagtaata acaatataaa tagaatagat atattgtcgg gcaacccgac 33301 agcatcttct ataccctata aagaaattat cgattactta aacaaaaaag cgggcaagca 33361 ttttaaacac aatacagcta aaacaaaaga ttttattaaa gcaagatgga atcaagattt 33421 taggttggag gattttaaaa aggtgattga tatcaaaaca gctgagtggc taaacacgga 33481 tagcgataaa taccttagac cagaaacact ttttggcagt aaatttgagg ggtacctcaa 33541 tcaaaaaata caaccaactg gcacggatca attggaacgc atgaagtacg acgaaagtta 33601 ttgggattag ggggatatta tgaaaccact attcagcgaa aagataaacg aaagcttgaa 33661 aaaatatcaa cctactcatg tcgaaaaagg attgaaatgt gagagatgtg gaagtgaata 33721 cgacttatat aagtttgctc ctactaaaaa acacccgaat ggttacgagt ataaagacgg 33781 ttgcaaatgt gaaatctatg aggaatataa gcgaaacaag caacggaaga taaacaacat 33841 attcaatcaa tcaaacgtta atccgtcttt aagagatgca acagtcaaaa actacaagcc 33901 acaaaatgaa aaacaagtac acgctaaaca aacagcaata gagtacgtac aaggcttctc 33961 tacaaaagaa ccaaaatcat taatattgca aggttcatac ggaactggta aaagccacct 34021 agcatacgct atcgcaaaag cagtcaaagc taaagggcat acggttgctt ttatgcacat 34081 accaatgttg atggatcgta tcaaagcgac atacaacaaa aatgcagtag agactacaga 34141 cgagctagtc agattgctaa gtgatattga tttacttgta ctagatgata tgggtgtaga 34201 aaacacagag cacactttaa ataaactttt cagcattgtt gataacagag taggtaaaaa 34261 caacatcttt acaactaact ttagtgataa agaactaaat caaaatatga actggcaacg 34321 tataaattcg agaatgaaaa aaagagcaag aaaagtaaga gtaatcggag acgatttcag 34381 ggagcgagat gcatggtaac caaagaattt ttaaaaacta aacttgagtg ttcagatatg 34441 tacgctcaga aactcataga tgaggcacag ggcgatgaaa ataggttgta cgacctattt 34501 atccaaaaac ttgcagaacg tcatacacgc cccgctatcg tcgaatatta aggagtgtta 34561 aaaatgccga aagaaaaata ttacttatac cgagaagatg gcacagaaga tattaaggtc 34621 atcaagtata aagacaacgt aaatgaggtt tattcgctca caggagccca tttcagcgac 34681 gaaaagaaaa ttatgactga tagtgaccta aaacgattca aaggcgctca cgggcttcta 34741 tatgagcaag aattaggttt acaagcaacg atatttgata tttagaggtg gacgatgagt 34801 aaatacaacg ctaagaaagt tgagtacaaa ggaattgtat ttgatagcaa agtagagtgt 34861 gaatattacc aatatttaga aagtaatatg aatggcacta attatgatca tatcgaaata 34921 caaccgaaat tcgaattatt accaaaacta gataaacaac gaaagattga atatattgca 34981 gacttcgcgt tatatctcga tggcaaactg attgaagtta tcgacattaa aggtatgcca 35041 accgaagtag caaaacttaa agctaagatt ttcagacata aatacagaaa cataaaactc 35101 aattggatat gtaaagcgcc taagtataca ggtaaaacat ggattacgta cgaggaatta 35161 attaaagcaa gacgagaacg caaaagagaa atgaagtgat ctaatgcaac aacaagcata 35221 tataaatgca acgattgata taaggatacc tacagaagtt gaatatcagc attttgatga 35281 tgtggataaa gaaaaagaag cgctggcaga ttacttatat aacaatcctg acgaaatact 35341 agagtatgac aatttaaaaa ttagaaacgt aaatgtagag gtggaataaa tgggcagtgt 35401 tgtaatcatt aataataaac catataaatt taacaatttt gaaaaaagaa ataatggcaa 35461 agcgtgggat aaatgctgga attgtttcta aacgtgttag aggttgttgg gagttttcag 35521 aagctttaga cgcgccttat ggcatgcacc taaaagaata tagagaaatg aaacaaatgg 35581 aaaagattaa acaagcgaga ctcgaacgtg aattggaaag agagcgaaag aaagaggctg 35641 agctacgtaa gaagaagcca catttgttta atgtacctca aaaacattca cgtgatccgt 35701 actggttcga tgtcacttat aaccaaatgt tcaagaaatg gagtgaagca taatgagcat 35761 aatcagtaac agaaaagtag atatgaacaa aacgcaagac aacgttaagc aacctgcgca 35821 ttacacatac ggcgacattg aaattataga ttttattgaa caagttacgg cacagtaccc 35881 accacaatta gcattcgcaa taggtaatgc aattaaatac ttgtctagag caccgttaaa 35941 gaatggtcat gaggatttag caaaggcgaa gttttacgtc gatagagtat ttgacttgtg 36001 ggagtgatga ccatgacaga tagcggacgt aaagaatact taaaacattt tttcggctct 36061 aagagatatc tgtatcagga taacgaacga gtggcacata tccatgtagt aaatggcact 36121 tattactttc acggtcatat cgtgccaggt tggcaaggtg tgaaaaagac atttgataca 36181 gcggaagagc ttgaaacata tataaagcaa agtgatttgg aatatgagga acagaagcaa WO 00/32825 PCT/IB99/02040 150 36241 ctaactttat tttaaaaggg cggaaacaat gaaaatcaaa attgaaaaag aaatgaattt 36301 acctgaactt atccaatggg cttgggataa ccccaagtta tcaggtaata aaagattcta 36361 ttcaaatgat gttgagcgca actgttttgt gacttttcat gttgatagca tcttatgtaa 36421 tgtgactgga tatgtatcaa ttaacgataa atttactgtt caagaggaga tataacaatg 36481 aaaatcaaag ttaaaaaaga aatgagatta gatgaattaa ttaaatgggc gcgagaaaat 36541 ccggatctat cacaaggaaa aatatttttt tcaacaggat ttagtgatgg attcgttcgt 36601 tttcatccaa atacaaataa gtgttcgacg tcaagtttta ttccaattga tatccccttc 36661 atagttgata ttgaaaaaga agtaacggaa gagactaagg ttgataggtt gattgaatta 36721 ttcgagattc aagaaggaga ctataactct acactatatg agaacactag tataaaagaa 36781 tgtttatatg gcagatgtgt gcctaccaaa gcattctaca tcttaaacga tgacctaact 36841 atgacgttaa tctggaaaga tggggagttg ctagtatgat gttgaaattt aaagcttggg 36901 ataaagataa aaaagttatg agtattattg acgaaatcga ttttaatagt gggtacattt 36961 tgatttcaac aggttataaa agtttcaatg aagtaaaact attacaatac acaggattta 37021 aagatgtgca cggtgtggag atttatgaag gggatattgt tcaagattgt tattcgagag 37081 aagtaagttt tatcgagttt aaagaaggag ccttttatat aacttttagc aatgtaactg 37141 aattactaag tgaaaatgac gatattattg aaattgttgg aaatattttt gaaaatgaga 37201 tgctattgga ggttatgaga tgacgttcac cttatcagat gaacaatata aaaatctttg 37261 tactaactct aacaagttat tagataaact tcacaaagca ttaaaagatc gtgaagagta 37321 caagaagcaa cgagatgagc ttattgggga tatagcgaag ttacgagatt gtaacaaaga 37381 tctagagaag aaagcaagcg catgggatag gtattgcaag agcgttgaaa aagatttaat 37441 aaacgaattc ggtaacgatg atgaaagagt taaattcgga atggaattaa acaataaaat 37501 ttttatggag gatgacacaa atgaataatc gcgaaaaaat cgaacagtcc gttattagtg 37561 ctagtgcgta taacggtaat gacacagagg ggttgctaaa agagattgag gacgtgtata 37621 agaaagcgca agcgtttgat gaaatacttg agggaatgac aaatgctatt caacattcag 37681 ttaaagaagg tattgaactt gatgaagcag tagggattat ggcaggtcaa gttgtctata 37741 aatatgagga ggaataggaa aatgactaac acattacaag taaaactatt atcaaaaaat 37801 gctagaatgc ccgaacgaaa tcataagacg gatgcaggtt atgacatatt ctcagctgaa 37861 actgtcgtac tcgaaccaca agaaaaagca gtgatcaaaa cagatgtagc tgtgagtata 37921 ccagagggct atgtcggact attaactagt cgtagtggtg taagtagtaa aacgtattta 37981 gtgattgaaa caggcaagat agacgcggga tatcatggca atttagggat taatatcaag 38041 aatgatgaag aacgtgatgg aatacccttt ttatatgatg atatagacgc tgaattagaa 38101 gatggattaa taagcatttt agatataaaa ggtaactatg tacaagatgg aagaggcata 38161 agaagagttt accaaatcaa caaaggcgat aaactagctc aattggttat cgtgcctata 38221 tggacaccgg aactaaagca agtggaggaa ttcgaaagtg tttcagaacg tggagcaaaa 38281 ggcttcggaa gtagcggagt gtaaagacat cttagatcga gttaaggagg ttttggggaa 38341 gtgacgcaat acttagtcac aacattcaaa gattcaacag gacgaccaca tgaacatatt 38401 actgtggcta gagataatca gacgtttaca gttattgagg cagagagtaa agaagaagcg 38461 aaagagaagt acgaggcaca agttaaaaga gatgcagtta ttaaagtggg tcagttgtat 38521 gaaaatataa gggagtgtgg gaaatgacgg atgttaaaat taaaactatt tcaggtggag 38581 tttattttgt aaaaacagct gaaccttttg aaaaatatgt tgaaagaatg acgagtttta 38641 atggttatat ttacgcaagt actataatca agaaaccaac gtatattaaa acagatacga 38701 ttgaatcaat cacacttatt gaggagcatg ggaaatgaat cagctgagaa ttttattaca 38761 tgacggtagt agtttgatat tacatgaaga tgaattattt aacgaaatag tatttgtttt 38821 ggacaatttt agaaatgatg atgactattt aacgatagaa aaagattatg gcagagaact 38881 tgtattgaac aaaggttata tagttgggat caatgttgag gaggcagatg atgattaaca 38941 tacctaaaat gaaattcccg aaaaagtaca ctgaaataat caaaaaatat aaaaataaag 39001 cacctgaaga aaaggctaag attgaagatg attttattaa agaaattaaa gataaagaca 39061 gtgaatttta cagtcctacg atggctaata tgaatgaata tgaattaagg gctatgttaa 39121 gaatgatgcc tagtttaatt gatactggag atgacaatga tgattaaaaa acttaaaaat 39181 atggatgggt tcgacatctt tattgttgga atactgtcat tattcggtat attcgcattg 39241 ctacttgtta tcacattgcc tatctataca gtggctagtt accaacacaa agaattacat 39301 caaggaacta ttacagataa atataacaag agacaagata aagaagacaa gttctatatt 39361 gtattagaca acaaacaagt cattgaaaat tccgacttat tattcaaaaa gaaatttgat 39421 agcgcagata tacaagctag gttaaaagta ggcgataagg tagaagttaa aacaatcggt 39481 tatagaatac actttttaaa tttatatccg gtcttatacg aagtaaagaa ggtagataaa 39541 caatgattaa acaaatacta agactattat tcttactagc aatgtatgag ttaggtaagt 39601 atgtaactga gcaagtgtat attatgatga cggctaatga tgatgtagag gcgccgagtg 39661 attacgtctt tcgagcggag gtgagtgaat aatgagaata tttatttatg atttgatcgt 39721 tttgctgttt gctttcttaa tatccatata tattattgat gatggagtga taataaatgc 39781 attaggaatt tttggtatgt ataaaattat agattccttt tcagaaaata ttataaagag 39841 gtagataaaa atgaacgagc aaataatagg aagcatatat actttagcag gaggtgttgt 39901 gctttattca gttaaagaga tttttaggta ttttacagat tctaact.tac aacgtaaaaa 3 9961 aatcaattta gaacaaatat atccgatata tttagattgt tttaaaaagg ctaaaaagat 40021 gattggagct tatattattc caacagaaca gcatgaattt ttagattttt ttgatattga 40081 agtctttaat aatttagata agcaaagtaa aaaagcgtat gaaaatgtta ttggatttag 40141 acaaatgatt aatttatcaa atagagttaa ggcaatggaa gattttaaga tgagtttcaa 40201 caatgaattt agtacaaatc agattttttt taatccttct tttgttatgg aaacaattgc 40261 tattataaat gaatatcaaa aagatatatc ttatttaaaa aatataatta ataaaatgaa WO 00/32825 PCT/IB99/02040 151 40321 tgaaaataga gcttataatc atattgatag ttttatcact tcagagtacc gacgaaaaat 40381 aaacgattat aatctttatc ttgataaatt tgaagaacag tttagtcaaa agtttaaaat 40441 aaacagaact tcgataaaag aaagaattat tattaattta aacaagagga gatttaaatg 40501 atgtggatta ctatgactat tgtatttgct atattgctat tagtttgtat cagtattaat 40561 agtgatcgtg caagagagat acaagcactt agatatatga atgattatct acttgatgaa 40621 gtagttaaaa ctaaagggta caacgggtta gaagaataca ggattgaatt gaagcgaatg 40681 aataacgata ttaaaaagta atttatatta tcggaggtat tgcattgaat gataaagatt 40741 gagaaacacg atatcaaaaa gcttgaagaa tacattcagc acatcgataa ctatcgaaga 40801 gagttgaaga tgcgagaata tgaattactt gaaagtcatg aaccagataa tgcgggagct 40861 ggcaaaagta atttgccggg taacccgatt gaacgatgtg caataaagaa gtttagtgat 40921 aacaggtaca atacattaag aaatatagtt aacggtgtag atagattgat aggtgaaagt 40981 gatgaggata cgcttgagtt attaaggttt agatattggg attgtcctat tggttgttat 41041 gaatgggaag atatagcaca ttactttggt acaagtaaga caagtatatt acgtagaagg 41101 aatgcactga tcgataagtt agcaaagtat attggttatg tgtagcggac ttttacccta 41161 tgtaagtccg cattaaaaca gtttattatg ttagtatcag attaatattt aaagttatta 41221 aatgctaata cgacgcatga acaagaggcg catcactatg tgatgtgtct ttttatttat 41281 gaggtatgaa catgttcaaa ctaattgtaa atacattact acacatcaag tatagatgag 41341 tcttgatact acttaagtta tataaggtga aacattatga tgactaaaga cgaacgtata 41401 cgattctata agtctaaaga atggcaaata acaagaaaaa gagtgctaga aagagataat 41461 tatgaatgtc aacaatgtaa gagagacggc aagttaacga catatgacaa aagcaagcgt 41521 aagtcgttgg atgtagatca tatattatcg ctagaacatc atccggagtt tgctcatgac 41581 ttaaacaatt tagaaacact gtgtattaaa tgtcacaaca aaaaagaaaa gagatttata 41641 aaaaaagaaa ataaatggaa agacgaaaaa tggtaaatac ccccgggtca aaaaaatcaa 41701 aagcgatc WO 00/32825 PCT/IB99/02040 152 Table 3 Name Position Name Position 1 770RF005 19572..21026 48 770RF052 1762..2013 2 770RF006 3976..5196 49 770RF053 37521..37757 3 770RF007 21871..23076 50 770RF054 22818..23060 4 770RF008 2120..3307 51 770RF055 17546..17788 5 770RF009 31946..32803 52 770RF058 18892..19122 6 770RF010 26092..26889 53 770RF059 34564..34785 7 770RF011 24441..25208 54 770RF064 29574..29795 8 770RF012 29788..30576 55 770RF065 28528..28746 9 770RF013 33620..34399 56 770RF066 27494..27703 10 770RF014 27760..28512 57 770RF069 38341..38547 11 770RF015 3291..4028 58 770RF070 36269..36475 12 770RF016 32867..33610 59 770RF071 40498..40701 13 770RF017 23269..23982 60 770RF072 38735..38938 14 770RF018 31169..31840 61 770RF073 30945..31148 15 770RF019 39851..40501 62 770RF074 38544..38738 16 770RF020 6926..7570 63 770RF075 13673..13870 17 770RF021 37762..38304 64 770RF077 25357..25605 18 770RF022 30605..31156 65 770RF079 29089..29280 19 770RF023 26903..27346 66 770RF080 35204..35389 20 770RF024 10700..11140 67 770RF085 24060..24242 21 770RF025 9707..10147 68 770RF092 39706..39876 22 770RF026 40729..41145 69 770RF094 32226..32393 23 770RF027 6518..6925 70 770RF096 13606..13773 24 770RF028 34795..35199 71 770RF098 7092..7256 25 770RF029 6117..6521 72 770RF102 29051..29212 26 770RF030 36478..36879 73 770RF104 34393..34551 27 770RF031 39151..39546 74 770RF109 18282..18434 28 770RF032 33892..34266 75 770RF112 39543..39692 29 770RF033 5758..6120 76 770RF117 27361..27501 30 770RF034 7886..8236 77 770RF118 38390..38530 31 770RF035 19258..19560 78 770RF120 36059..36199 32 770RF036 36876..37223 79 770RF124 33699..33833 33 770RF037 102..446 80 770RF128 14221..14355 34 770RF038 34908..35219 81 770RF130 15675..15806 35 770RF039 37220..37528 82 770RF133 8414..8542 36 770RF040 41377..41676 83 770RF140 13113..13235 37 770RF041 35454..35753 84 770RF147 7029..7148 38 770RF042 5490..5774 85 770RF149 30668..30787 39 770RF043 29304..29564 86 770RF151 31837..31953 40 770RF044 18481..18768 87 770RF155 30278..30391 41 770RF045 5216..5500 88 770RF157 4044..4157 42 770RF046 25663..25935 89 770RF167 20692..20799 43 770RF047 11159..11425 90 770RF175 35717..35821 44 770RF048 28776..29039 91 770RF176 6836..6940 45 770RF049 36013..36255 92 770RF178 35390..35491 46 770RF050 35753..36007 93 770RF179 8318..8419 47 770RF051 38931..39167 94 770RF182 29268..29564 WO 00/32825 PCT/IB99/02040 153 Table 4 770RF017 sequence 23982 atgacgcataatatagaaaaacgcattaataaattaaaaacttct 1 M T H N I E K R I N K L K T S 23937 ggaaatccaaaatttaaaaagttagattcagatattcactattta 16 G N P K F K K L D S D I H Y L 23892 ctcaagagatttgaaggtgaaaaaaaccataaaggtttttatcca 31 L K R F E G E K N H K G F Y P 23847 aagtttaaacaaggagaaatagtttttgtagatttcggtataaac 46 K F K Q G E I V F V D F G I N 23802 gttaataaagaattttctaattcacactttgcaatagtgatgaat 61 V N K E F S N S H F A I V M N 23757 aaaaatgattctaatacggaggatatagtaaatgttattccctta 76 K N D S N T E D I V N V I P L 23712 tcctctaaagaaaacaaaaagtatttaaagatgaattttgatttg 91 S S K E N K K Y L K M N F D L 23667 aaatgggagtattatttaagattgtttttaaatttaattagcgcg 106 K W E Y Y L R L F L N L I S A 23622 caaaataattcagctatattaaaagaagttttcgataaaaaatac 121 Q N N S A I L K E V F D K K Y 23577 caaaaaaacaacacagaattcatcactaaagattattttattgaa 136 Q K N N T E F I T K D Y F I E 23532 tttatatctgatagtttagaaattgaaaataaattaaataaaatt 151 F I S D S L E I E N K L N K I 23487 gacagaaacattaataacatagtatcagcaattgataaggtaaaa 166 D R N I N N I V S A I D K V K 23442 aaattaaaaggtaatagttacgcttgcataaattctttccagccg 181 K L K G N S Y A C I N S F Q P 23397 attagtaagtttcgcataagaaaagttttaccccaaaaaattaaa 196 I S K F R I R K V L P Q K I K 23352 aatccagtaatagattcttcggatattatgttactgataaataga 211 N P V I D S S D I M L L I N R 23307 attaataataatatattgcagatccctgatataagatga 23269 226 I N N N I L Q I P D I R * WO 00/32825 PCT/IB99/02040 154 Physico-chemical parameters of ORF 770RF017 1 MTHNIEKRIN KLKTSGNPKF KKLDSDIHYL LKRFEGEKNH KGFYPKFKQG EIVFVDFGIN 61 VNKEFSNSHF AIVMNKNDSN TEDIVNVIPL SSKENKKYLK MNFDLKWEYY LRLFLNLISA 121 QNNSAILKEV FDKKYQKNNT EFITKDYFIE FISDSLEIEN KLNKIDRNIN NIVSAIDKVK 181 KLKGNSYACI NSFQPISKFR IRKVLPQKIK NPVIDSSDIM LLINRINNNI LQIPDIR Number of amino acids: 237 Average molecular weight (Daltons): 27887.38 Mean amino acid weight (Daltons): 117.67 Monoisotopic molecular weight (Daltons): 27869.83 Mean amino acid monoisotopic weight (Daltons): 117.59 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d I er in Swissprot d 1 er - in Swissprot Ala A 5 2.11% 7.58% Cys C 1 0.42% 1.66% Asp D 14 5.91% 5.28% Glu E 13 5.49% 6.37% Phe F 16 6.75% 4.09% Gly G 6 2.53% 6.84% His H 4 1.69% 2.24% Ile I 29 12.24 5.81% Lys K 33 13.92 5.95% Leu L 19 8.02% 9.42% Met M 4 1.69% 2.37% Asn N 30 12.66 4.45% lPro P 7 2.95% 4.9% Gln Q 6 2.53% 3.97% Arg _R 8 -3.38% 5.16% Ser S 17 7.17% 7.12% Thr T 5 2.11% 5.67% Val V 11 4.64% 6.58% Trp W 1 0.42% 1.23% Tyr Y 8 3.38% 3.18% Number of acidic (negative) amino acids (ED): 27 11.39% Number of basic (positive) amino acids (KR): 41 17.30% Total charge (KRED): 68 28.69% Net charge (KR - ED): 14 5.91% Theoritical pI: 10.01 Total linear charge density: 0.30 Average hydrophobicity: -5.37 Ratio of hydrophilicity to hydrophobicity: 1.41 Percentage of hydrophilic amino acid: 57.81% Percentage of hydrophobic amino acid: 42.19 0 / Ratio of %hydrophilic to %hydrophobic: 1.37 WO 00/32825 PCT/IB99/02040 155 770RF019 sequence 39851 atgaacgagcaaataataggaagcatatatactttagcaggaggt 1 M N E Q I I G S I Y T L A G G 39896 gttgtgctttattcagttaaagagatttttaggtattttacagat 16 V V L Y S V K E I F R Y F T D 39941 tctaacttacaacgtaaaaaaatcaatttagaacaaatatatccg 31 S N L Q R K K I N L E Q I Y P 39986 atatatttagattgttttaaaaaggctaaaaagatgattggagct 46 I Y L D C F K K A K K M I G A 40031 tatattattccaacagaacagcatgaatttttagatttttttgat 61 Y I I P T E Q H E F L D F F D 40076 attgaagtctttaataatttagataagcaaagtaaaaaagcgtat 76 I E V F N N L D K Q S K K A Y 40121 gaaaatgttattggatttagacaaatgattaatttatcaaataga 91 E N V I G F R Q M I N L S N R 40166 gttaaggcaatggaagattttaagatgagtttcaacaatgaattt 106 V K A M E D F K M S F N N E F 40211 agtacaaatcagattttttttaatccttcttttgttatggaaaca 121 S T N Q I F F N P S F V M E T 40256 attgctattataaatgaatatcaaaaagatatatcttatttaaaa 136 I A I I N E Y Q K D I S Y L K 40301 aatataattaataaaatgaatgaaaatagagcttataatcatatt 151 N I I N K M N E N R A Y N H I 40346 gatagttttatcacttcagagtaccgacgaaaaataaacgattat 166 D S F I T S E Y R R K I N D Y 40391 aatctttatcttgataaatttgaagaacagtttagtcaaaagttt 181 N L Y L D K F E E Q F S Q K F 40436 aaaataaacagaacttcgataaaagaaagaattattattaattta 196 K I N R T S I K E R I I I N L 40481 aacaagaggagatttaaatga 40501 211 N K R R F K * WO 00/32825 PCT/IB99/02040 156 Physico-chemical parameters of ORF 770RF019 1 MNEQIIGSIY TLAGGVVLYS VKEIFRYFTD SNLQRKKINL EQIYPIYLDC FKKAKKMIGA 61 YIIPTEQHEF LDFFDIEVFN NLDKQSKKAY ENVIGFRQMI NLSNRVKAME DFKMSFNNEF 121 STNQIFFNPS FVMETIAIIN EYQKDISYLK NIINKMNENR AYNHIDSFIT SEYRRKINDY 181 NLYLDKFEEQ FSQKFKINRT SIKERIIINL NKRRFK Number of amino acids: 216 Average molecular weight (Daltons): 26026.06 Mean amino acid weight (Daltons): 120.49 Monoisotopic molecular weight (Daltons): 26009.34 Mean amino acid monoisotopic weight (Daltons): 120.41 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d 1 er in Swissprot d I er in Swissprot Ala A 7 3.24% 7.58% Cys C 1 0.46% 1.66% Asp D 10 4.63% 5.28% Glu E 16 7.41% 6.37% Phe F 19 8.80% 4.09% Gly G 5 2.31% 6.84% His H 2 0.93% 2.24% Ile I 28 12.96 5.81% Lys K 22 10.19 5.95% Leu L 12 5.56% 9.42% Met M 7 3.24% 2.37% Asn N 23 10.65 4.45% Pro P 3 1.39% 4.9% Gln Q 10 4.63% 3.97% Arg R 11 5.09% 5.16% Ser S 13 6.02% 7.12% Thr T 7 3.24% 5.67% Val V 7 3.24% 6.58% Trp W 0 0.00% 1.23% Tyr Y 13 6.02% 3.18% Number of acidic (negative) amino acids (ED): 26 12.04% Number of basic (positive) amino acids (KR): 33 15.28% Total charge (KRED): 59 27.31% Net charge (KR - ED): 7 3.24% Theoritical pI: 9.52 Total linear charge density: 0.28 Average hydrophobicity: -4.84 Ratio of hydrophilicity to hydrophobicity: 1.37 Percentage of hydrophilic amino acid: 54.17% Percentage of hydrophobic amino acid: 45.83% Ratio of %hydrophilic to %hydrophobic: 1.18 - WO 00/32825 PCT/IB99/02040 157 770RF043 sequence 29304 atgtattacgaaataggcgaaatcatacgcaaaaatattcatgtt 1 M Y Y E I G E I I R K N I H V 29349 aacggattcgattttaagctattcattttaaaaggtcatatgggc 16 N G F D F K L F I L K G H M G 29394 atatcaatacaagttaaagatatgaacaacgtaccaattaaacat 31 I S I Q V K D M N N V P I K H 29439 gcttatgtcgtagatgagaatgacttagatatggcatcagactta 46 A Y V V D E N D L D M A S D L 29484 tttaaccaagcaatagatgaatggattgaagagaacacagacgaa 61 F N Q A I D E W I E E N T D E 29529 caggacagactaattaacttagtcatgaaatggtag 29564 76 Q D R L I N L V M K W * WO 00/32825 PCT/IB99/02040 158 Physico-chemical parameters of ORF 770RF043 1 MYYEIGEIIR KNIHVNGFDF KLFILKGHMG ISIQVKDMNN VPIKHAYVVD ENDLDMASDL 61 FNQAIDEWIE ENTDEQDRLI NLVMKW Number of amino acids: 86 Average molecular weight (Daltons): 10186.68 Mean amino acid weight (Daltons): 118.45 Monoisotopic molecular weight (Daltons): 10180.02 Mean amino acid monoisotopic weight (Daltons): 118.37 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d I er in Swissprot d 1 er in Swissprot Ala A 3 3.49% 7.58% Cys C 0 0.00% 1.66% Asp D 9 10.47 5.28% Glu E 7 8.14% 6.37% % 11 Phe F 4 4.65% 4.09% Gly G 4 4.65% 6.84% His H 3 3.49% 2.24% Ile I 11 12.79 5.81% Lys K 6 6.98% 5.95% Leu L 6 6.98% 9.42% Met M 5 5.81% 2.37% Asn N 8 9.30% 4.45% Pro P 1 1.16% 4.9% Gln Q 3 3.49% 3.97% Arg R 2 2.33% 5.16% Ser S 2 2.33% 7.12% Thr T 1 1.16% 5.67% Val V 6 6.98% 6.58% Trp W 2 2.33% 1.23% Tyr JY 3 3.49% 3.18% Number of acidic (negative) amino acids (ED): 16 18.60% Number of basic (positive) amino acids (KR): 8 9.30% Total charge (KRED): 24 27.91% Net charge (KR - ED): -8 9.30% Theoritical pI: 4.38 Total linear charge density: 0.30 Average hydrophobicity: -2.80 Ratio of hydrophilicity to hydrophobicity: 1.19 Percentage of hydrophilic amino acid: 48.84% Percentage of hydrophobic amino acid: 51.16% Ratio of %hydrophilic to %hydrophobic: 0.95 WO 00/32825 PCT/IB99/02040 159 770RF102 sequence 29051 atgagcaacatttataaaagctacctagtagcagtattatgcttc 1 M S N I Y K S Y L V A V L C F 29096 acagtcttagcgattgtacttatgccgtttctatacttcactaca 16 T V L A I V L M P F L Y F T T 29141 gcatggtcaattgcgggattcgcaagtatcgcaacattcatgtac 31 A W S I A G F A S I A T F M Y 29186 tacaaagaatgctttttcaaagaataa 29212 46 Y K E C F F K E * WO 00/32825 PCT/IB99/02040 160 Physico-chemical parameters of ORF 770RF102 1 MSNIYKSYLV AVLCFTVLAI VLMPFLYFTT AWSIAGFASI ATFMYYKECF FKE Number of amino acids: 53 Average molecular weight (Daltons): 6155.42 Mean amino acid weight (Daltons): 116.14 Monoisotopic molecular weight (Daltons): 6151.07 Mean amino acid monoisotopic weight (Daltons): 116.06 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d I er in Swissprot d I er in Swissprot Ala A 6 11.32 7.58% Cys C 2 3.77 1.66% Asp D 0 0.00% 5.28% Glu E 2 77 6.37% Phe F 7 13.21 4.09% Gly G 1 1.89 6.84% His H 0 0.00% 2.24% Ile I 4 55 5.81% Lys K 3 5.66% 5.95% Leu L 5 9.43 9.42% Met M 3 5.66% 2.37% Asn N 1 1.89 4.45% Pro P 1 1.89% 4.9% Gln Q 0 0.00 3.97% Arg R 0 0.00% 5.16% Ser S 4 7.55 7.12% % Thr T 4 7.55% 5.67% Val V 4 % 5 6.58% Trp W 1 1.89% 1.23% Tyr Y 5 9%43 3.18% Number of acidic (negative) amino acids (ED): 2 3.77% Number of basic (positive) amino acids (KR): 3 5.66% Total charge (KRED): 5 9.43% Net charge (KR - ED): 1 1.89% Theoritical pI: 8.18 Total linear charge density: 0.13 Average hydrophobicity: 10.81 Ratio of hydrophilicity to hydrophobicity: 0.40 Percentage of hydrophilic amino acid: 28.30% Percentage of hydrophobic amino acid: 71.70% WO 00/32825 PCT/IB99/02040 161 Ratio of %hydrophilic to %hydrophobic: 0.39 WO 00/32825 PCT/IB99/02040 162 770RF104 sequence 34393 atggtaaccaaagaatttttaaaaactaaacttgagtgttcagat 1 M V T K E F L K T K L E C S D 34438 atgtacgctcagaaactcatagatgaggcacagggcgatgaaaat 16 M Y A Q K L I D E A Q G D E N 34483 aggttgtacgacctatttatccaaaaacttgcagaacgtcataca 31 R L Y D L F I Q K L A E R H T 34528 cgccccgctatcgtcgaatattaa 34551 46 R P A I V E Y * WO 00/32825 PCT/IB99/02040 163 Physico-chemical parameters of ORF 770RF104 1 MVTKEFLKTK LECSDMYAQK LIDEAQGDEN RLYDLFIQKL AERHTRPAIV EY Number of amino acids: 52 Average molecular weight (Daltons): 6193.13 Mean amino acid weight (Daltons): 119.10 Monoisotopic molecular weight (Daltons): 6189.12 Mean amino acid monoisotopic weight (Daltons): 119.02 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d I er in Swissprot d I er in Swissprot Ala A 4 7.69 7.58% Cys C 1 1.92% 1.66% 7.69 11.54 Asp D 4 6 5.28% Glu E 6 1 6.37% Phe F 2 3.85 4.09% Gly G 1 1.92% 6.84% His H 1 1.92 2.24% Ile I 3 5.77% 5.81% Lys K 5 9.62 5.95% Leu L 6 11.54 9.42% Met M 2 3.85 2.37% Asn N 1 1.92% 4.45% Pro P 1 1.92 4.9% Gln Q 3 5.77% 3.97% Arg R 3 5.77 5.16% Ser S 1 1.92% 7.12% Thr T 3 77 5.67% Val V 2 3.85% 6.58% Trp W 0 0.00 1.23% Tyr Y 3 5.77% 3.18% Number of acidic (negative) amino acids (ED): 10 19.23% Number of basic (positive) amino acids (KR): 8 15.38% Total charge (KRED): 18 34.62% Net charge (KR - ED): -2 3.85% Theoritical pI: 5.03 Total linear charge density: 0.38 Average hydrophobicity: -5.81 ~ Ratio of hydrophilicity to hydrophobicity: 1.47 Percentage of hydrophilic amino acid: 53.85% Percentage of hydrophobic amino acid: 46.15% WO 00/32825 PCT/IB99/02040 164 Ratio of %hydrophilic to %hydrophobic: 1.17 WO 00/32825 PCT/IB99/02040 165 770RF182 sequence 29268 atgttcaatataaaacgaaaaacggaggaagtcaagatgtattac 1 M F N I K R K T E E V K M Y Y 29313 gaaataggcgaaatcatacgcaaaaatattcatgttaacggattc 16 E I G E I I R K N I H V N G F 29358 gattttaagctattcattttaaaaggtcatatgggcatatcaata 31 D F K L F I L K G H M G I S I 29403 caagttaaagatatgaacaacgtaccaattaaacatgcttatgtc 46 Q V K D M N N V P I K H A Y V 29448 gtagatgagaatgacttagatatggcatcagacttatttaaccaa 61 V D E N D L D M A S D L F N Q 29493 gcaatagatgaatggattgaagagaacacagacgaacaggacaga 76 A I D E W I E E N T D E Q D R 29538 ctaattaacttagtcatgaaatggtag 29564 91 L I N L V M K W * WO 00/32825 PCT/IB99/02040 166 Physico-chemical parameters of ORF 770RF182 1 MFNIKRKTEE VKMYYEIGEI IRKNIHVNGF DFKLFILKGH MGISIQVKDM NNVPIKHAYV 61 VDENDLDMAS DLFNQAIDEW IEENTDEQDR LINLVMKW Number of amino acids: 98 Average molecular weight (Daltons): 11691.50 Mean amino acid weight (Daltons): 119.30 Monoisotopic molecular weight (Daltons): 11683.84 Mean amino acid monoisotopic weight (Daltons): 119.22 Amino acid composition Aci Symbo Numb % Average % Aci Symbo Numb % Average % d I er in Swissprot d 1 er in Swissprot Ala A 3 3.06 7.58% Cys C 0 0.00% 1.66% Asp D 9 9.18 5.28% Glu E 9 9.18% 6.37% Phe F 5 5.10 4.09% Gly G 4 4.08% 6.84% His H 3 06 2.24% Ile I 12 12.24 5.81% Lys K 9 9.18 5.95% Leu L 6 6.12% 9.42% Met M 6 6.12 2.37% Asn N 9 9.18% 4.45% Pro P 1 1.02 4.9% Gln Q 3 3.06% 3.97% Arg R 3 3.06 5.16% Ser S 2 2.04% 7.12% Thr T 2 204 5.67% Val V 7 7.14% 6.58% 1% Trp IW 12 2.04 1.23% Tyr Y 3 13.06% 3.18% Number of acidic (negative) amino acids (ED): 18 18.37% Number of basic (positive) amino acids (KR): 12 12.24% Total charge (KRED): 30 30.61% Net charge (KR - ED): -6 6.12% Theoritical pI: 4.76 Total linear charge density: 0.33 Average hydrophobicity: -3.89 Ratio of hydrophilicity to hydrophobicity: 1.28 WO 00/32825 PCT/IB99/02040 167 Percentage of hydrophilic amino acid: 51.02% Percentage of hydrophobic amino acid: 48.98% Ratio of %hydrophilic to %hydrophobic: 1.04 WO 00/32825 PCT/IB99/02040 168 Table 5 BLASTP 2.0.8 [Jan-05-1999] Query= sid100017|lanI77ORF017 Phage 77 ORF 123269-239821-3 (237 letters) Database: nr 393,678 sequences; 120,452,765 total letters Score E Sequences producing significant alignments: (bits) Value gij4493986|emb|CAB39045.1| (AL034559) predicted using hexExon; ... 41 0.010 gil7306071splP23250IRPI1_YEAST NEGATIVE RAS PROTEIN REGULATOR P... 38 0.053 gil3097044|emb|CAA752991 (Y15035) K1R [Cowpox virus] 38 0.090 gil2l46245|pir||S73794 hypothetical protein H91_orf180 - Mycopl ... 38 0.090 gij83910|pirl|S04682 ribosomal protein varl - yeast (Candida gl... 37 0.15 gil133135|sp|P21358|RMAR_CANGA MITOCHONDRIAL RIBOSOMAL PROTEIN ... 37 0.15 gil2l28843|pir|IH64475 hypothetical protein MJ1409 - Methanococ... 36 0.20 gi|5l070l7|gblAAD39926.11AF126285_2 (AF126285) RNA polymerase [ ... 36 0.35 gil2l46210pir|IS73342 hypothetical protein E07_orf166 - Mycopl ... 35 0.60 Database: swissprot 79,449 sequences; 28,874,452 total letters Score E Sequences producing significant alignments: (bits) Value spIP23250 RPI1_YEAST NEGATIVE RAS PROTEIN REGULATOR PROTEIN. 38 0.014 sp1P21358 RMARCANGA MITOCHONDRIAL RIBOSOMAL PROTEIN VARl. 37 0.040 sp1Q21444 LDLCCAEEL LDLC PROTEIN HOMOLOG. 34 0.35 sp|P27240 RFAYECOLI LIPOPOLYSACCHARIDE CORE BIOSYNTHESIS PROT. 33 0.46 sp|P53192 YGCOYEAST HYPOTHETICAL 27.1 KD PROTEIN IN ALKl-CKBl. 33 0.60 sp1P32908 SMC1_YEAST CHROMOSOME SEGREGATION PROTEIN SMCl (DA-B. 33 0.60 sp|P54683 TAGBDICDI PRESTALK-SPECIFIC PROTEIN TAGB PRECURSOR 32 0.78 sp$Q03100 CYAADICDI ADENYLATE CYCLASE, AGGREGATION SPECIFIC 32 0.78 WO 00/32825 PCT/IB99/02040 169 BLASTP 2.0.8 [Jan-05-1999] Query= sid|100019IlanI77ORF019 Phage 77 ORF139851-4050112 (216 letters) Database: nr 373,355 sequences; 114,214,446 total letters Score E Sequences producing significant alignments: (bits) Value gil3341966ldbjlBAA319321 (AB009866) orf 59 [bacteriophage phi PVL] 437 e-122 gil2689911 (AE000792) B. burgdorferi predicted coding region BB... 38 0.058 gil11715891embICAA645741 (X95275) frameshift (Plasmodium falcip ... 37 0.10 gil4493986|embjCAB39045.1| (AL034559) predicted using hexExon; ... 36 0.23 giJ141257|spIP18019|YPI9_CLOPE HYPOTHETICAL 14.5 KD PROTEIN (OR... 36 0.29 gil133412|spIP27059IRPOBASTLO DNA-DIRECTED RNA POLYMERASE BETA... 35 0.51 giJ3122231|splQ58851|HISX METJA HISTIDINOL DEHYDROGENASE (HDH) ... 35 0.51 gil3649757|emb|CAB11106.1I (Z98547) predicted using hexExon; MA... 34 0.66 gil2688313 (AE001146) sensory transduction histidine kinase, pu ... 34 0.87 Database: swissprot 79,449 sequences; 28,874,452 total letters Score E Sequences producing significant alignments: (bits) Value spIP18019 YPI9_CLOPE HYPOTHETICAL 14.5 KD PROTEIN (ORF9). 36 0.079 spjQ58851 HISXMETJA HISTIDINOL DEHYDROGENASE (EC 1.1.1.23) (H. 35 0.14 spIP27059 RPOBASTLO DNA-DIRECTED RNA POLYMERASE BETA CHAIN (E. 35 0.14 spjQ02224 CENEHUMAN CENTROMERIC PROTEIN E (CENP-E PROTEIN). 34 0.31 sptP04931 ARP PLAFA ASPARAGINE-RICH PROTEIN (AG319) (ARP) (FRA.. 33 0.53 spiP18011 IPABSHIFL 62 KD MEMBRANE ANTIGEN. 32 0.69 sp1P18709 VTA2_XENLA VITELLOGENIN A2 PRECURSOR (VTG A2) [CONTA.. 32 0.90 sp|Q64409 CP3H_CAVPO CYTOCHROME P450 3A17 (EC 1.14.14.1) (CYPI.. 32 0.90 sp1P21358 RMARCANGA MITOCHONDRIAL RIBOSOMAL PROTEIN VAR1. 32 0.90 splQ03945 IPABSHIDY 62 KD MEMBRANE ANTIGEN. 32 1.2 WO 00/32825 PCT/IB99/02040 170 BLASTP 2.0.8 [Jan-05-1999] Query= sid11000431lan177ORF043 Phage 77 ORF129304-2956413 (86 letters) Database: nr 373,355 sequences; 114,214,446 total letters Score E Sequences producing significant alignments: (bits) Value gil3341947ldbjlBAA31913| (AB009866) orf 39 [bacteriophage phi PVL 182 6e-46 gil744518|prf||2014422A FKBP-rapamycin-associated protein [Homo ... 32 0.84 gil1169736|spIP42346|FRAP_RAT FKBP-RAPAMYCIN ASSOCIATED PROTEIN... 32 0.84 gill69735|spjP42345|FRAPHUMAN FKBP-RAPAMYCIN ASSOCIATED PROTE... 32 0.84 gil3282239 (U88966) rapamycin associated protein FRAP2 [Homo sa ... 32 0.84 gi|3875402lembiCAA981221 (Z73906) cDNA EST EMBL:D64544 comes fr ... 31 2.5 gil10847921pir||S54091 hypothetical protein YPRO70w - yeast (Sa... 30 4.2 Database: swissprot 79,449 sequences; 28,874,452 total letters Score E Sequences producing significant alignments: (bits) Value sp1P42345 FRAPHUMAN FKBP-RAPAMYCIN ASSOCIATED PROTEIN (FRAP) . 32 0.24 sp1P42346 FRAPRAT FKBP-RAPAMYCIN ASSOCIATED PROTEIN (FRAP) (R. 32 0.24 spIP34554 YNP1_CAEEL HYPOTHETICAL 42.2 KD PROTEIN T05G5.1 IN C. 28 3.5 spjQ24118 LIODROME LINOTTE PROTEIN. 28 3.5 sp|P80034 ACH2_BOMMO ANTICHYMOTRYPSIN II (ACHY-II). 28 3.5 sp|P22922 A1ATBOMMO ANTITRYPSIN PRECURSOR (AT). 28 3.5 spjQ44363 TRAAAGRT6 CONJUGAL TRANSFER PROTEIN TRAA. 28 3.5 sp|P38255 YBU5_YEAST HYPOTHETICAL 51.3 KD PROTEIN IN PHO5-VPS1. 27 6.0 sp|P55822 SH3BHUMAN SH3BGR PROTEIN (21-GLUTAMIC ACID-RICH PRO. 27 7.9 sp1Q58482 YA82_METJA HYPOTHETICAL PROTEIN MJ1082. 27 7.9 spIP34252 YKK8_YEAST HYPOTHETICAL 52.3 KD PROTEIN IN HAP4-AAT1. 27 7.9 WO 00/32825 PCT/IB99/02040 171 BLASTP 2.0.8 [Jan-05-1999) Query= sidI00102|lan|77ORF102 Phage 77 ORF129051-29212|2 (53 letters) Database: nr 373,355 sequences; 114,214,446 total letters Score E Sequences producing significant alignments: (bits) Value gil3341946ldbj|BAA319121 (AB009866) orf 38 [bacteriophage phi PVL] 96 3e-20 gil43252881gblAAD173151 (AF123593) voltage-dependent sodium cha ... 28 7.1 gil2649684 (AE001040) A. fulgidus predicted coding region AF092 ... 28 9.3 Database: swissprot 79,449 sequences; 28,874,452 total letters Score E Sequences producing significant alignments: (bits) Value spIP42087 HUTMBACSU PUTATIVE HISTIDINE PERMEASE. 26 7.1 sp1P04775 CIN2_RAT SODIUM CHANNEL PROTEIN, BRAIN II ALPHA SUBU ... 26 9.2 spIP42619 YQJFECOLI HYPOTHETICAL 17.2 KD PROTEIN IN EXUR-TDCC... 26 9.2 WO 00/32825 PCT/IB99/02040 172 BLASTP 2.0.8 [Jan-05-1999] Query= sid|100104|lanI77ORF104 Phage 77 ORF134393-3455111 (52 letters) Database: nr 373,355 sequences; 114,214,446 total letters Score E Sequences producing significant alignments: (bits) Value giJ2315523 (AF016452) similar to the leucine-rich domains found... 29 4.2 gil4377168|gb|AAD18990| (AE001666) CT711 hypothetical protein [ ... 29 5.4 gil3882171ldbj|BAA34445| (AB018268) KIAA0725 protein [Homo sapi... 28 9.3 Database: swissprot 79,449 sequences; 28,874,452 total letters Score E Sequences producing significant alignments: (bits) Value splP04879 RRPPVSVIG RNA POLYMERASE ALPHA SUBUNIT (EC 2.7.7.48. 27 5.4 spIP04880 RRPPVSVIM RNA POLYMERASE ALPHA SUBUNIT (EC 2.7.7.48. 27 5.4 spIQ13946 CN7AHUMAN HIGH-AFFINITY CAMP-SPECIFIC 3,5-CYCLIC . 26 7.1 splP35381 ATPADROME ATP SYNTHASE ALPHA CHAIN, MITOCHONDRIAL P. 26 9.3 sp1P54659 MVPBDICDI MAJOR VAULT PROTEIN BETA (MVP-BETA). 26 9.3 spjP40397 YHXC_BACSU HYPOTHETICAL OXIDOREDUCTASE IN APRE-COMK . 26 9.3 WO 00/32825 PCT/IB99/02040 173 BLASTP 2.0.8 [Jan-05-1999] Query= sid11227481lan|770RF182 Phage 77 ORF129268-2956413 (98 letters) Database: nr 393,678 sequences; 120,452,765 total letters Score E Sequences producing significant alignments: (bits) Value gil3341947|dbjlBAA31913.1| (AB009866) orf 39 [bacteriophage phi.. 182 8e-46 gil1084792|pir||S54091 hypothetical protein YPR070w - yeast (Sa.. 35 0.13 gill697361spIP42346|FRAPRAT FKBP-RAPAMYCIN ASSOCIATED PROTEIN.. 32 1.1 gil744518|prfI|2014422A FKBP-rapamycin-associated protein [Homo.. 32 1.1 giJ5051381|emb|CAB44736.1| (AL049653) dJ647M16.2 (FK506 binding.. 32 1.1 gil48267301refINP_004949.lpFRAP1| FK506 binding protein 12-rap.. 32 1.1 giJ3282239 (U88966) rapamycin associated protein FRAP2 [Homo sa.. 32 1.1 Database: swissprot 79,909 sequences; 29,054,478 total letters Score E Sequences producing significant alignments: (bits) Value spIP42345 FRAPHUMAN FKBP-RAPAMYCIN ASSOCIATED PROTEIN (FRAP) . 32 0.29 sp1P42346 FRAPRAT FKBP-RAPAMYCIN ASSOCIATED PROTEIN (FRAP) (R. 32 0.29 spIP40557 YIA5_YEAST PUTATIVE DISULFIDE ISOMERASE YIL005W PREC. 29 3.3 sp1Q24118 LIODROME LINOTTE PROTEIN. 28 4.4 sp1Q44363 TRAAAGRT6 CONJUGAL TRANSFER PROTEIN TRAA. 28 4.4 spIP80034 ACH2_BOMMO ANTICHYMOTRYPSIN II (ACHY-II). 28 4.4 spjP34554 YNP1_CAEEL HYPOTHETICAL 42.2 KD PROTEIN T05G5.1 IN C. 28 4.4 sp|P22922 AlATBOMMO ANTITRYPSIN PRECURSOR (AT). 28 4.4 WO 00/32825 PCT/IB99/02040 174 Table 6 1st 3rd position 2nd position position (5'end) (3' end) U C A G Phe Ser Tyr Cys U Phe Ser Tyr Cys C Leu Ser Stop Stop A Leu Ser Stop Trp G Leu Pro His Arg U Leu Pro His Arg C C Leu Pro Gin Arg A Leu Pro Gin Ara G lie Thr Asn Ser U A lie Thr Asn Ser C Ile Thr Lys Arg A Met Thr Lvs Arq G Val Ala Asp Gly U Val Ala Asp Gly C Val Ala Giu Gly A Val Ala Glu GIv G WO 00/32825 PCT/IB99/02040 175 Table 7 Bacteriophage 3A, complete genome sequence 1 caaacgctag caacgcggat aaatttttca tgaaaggggg tctttatatg aagttaacaa aaaaacagct 71 aaaagaatat atagaagatt acaaaaaatc tgatgacata ttaattaatt tgtatataga aacatatgaa 141 ttttattgtc ggttaagaga tgaacttaaa aatagtgatt taatgataga gcatacaaac aaggctggtg 211 cgagcaatat tattaagaat ccattaagca tagaactgac aaaaacagtt caaacactaa ataacttact 281 caagtctatg ggtttaactg cagcacaaag aaaaaagata gttcaagaag aaggtggatt cggtgactat 351 taaagtttta aatgaacctt caccaaaact attaacaaca tggtatgcag agcaagtcac tcaagggaaa 421 ataaaaacaa gcaaatatgt tagaaaagaa tgtgagagac atcttagata tctagaaaat ggaggtaaat 491 gggtatttga tgaagaatta gcgcatcgtc ctattcgatt tatagaaaag ttttgtaaac cttccaaagg 561 atctaaacgt caacttgtat tacagccatg gcaacatttt attatcggca gtttgtttgg ttgggttcat 631 aaagaaacaa aactgcgcag gtttaaagaa gctttgatat ttatggggcg aaaaaatggt aaaacaacca 701 ctatttctgg ggttgctaac tatgctgtat cacaagatgg agaaaatggt gcagaaattc atttgttagc 771 aaacgtaatg aaacaagcta ggattctatt tgatgaatct aaggcgatga ttaaagctag cccaaagctt 841 gataaaaatt tcagaacatt aagagatgaa atccattatg acgcaacgat atcaaaaatt atgccccaag 911 catcagatag cgataagtta gatggattga atacacacat ggggattttt gatgaaattc atgaatttaa 981 agactataaa ttgatttcag ttataaaaaa ctcaagagct gcaaggttac aacctcttct catctacatt 1051 acgacagcag ggtatcaatt agatggtcca cttgttgata tggtagaagc gggaagagac accttagatc 1121 aaatcataga agacgaaaga actttttatt atttagcatc tttggatgat gacgatgata ttaatgattc 1191 gtcgaactgg ataaaagcaa atcccaactt aggtgtctct ataaatttag atgagatgaa agaagagtgg 1261 gaaaaagcta agagaacacc agctgaacgt ggagatttta taaccaaaag gtttaatatc tttgctaata 1331 atgacgagat gagttttatt gattacccaa cactccaaaa aaataatgaa attgtttctt tagaagagct 1401 ggaaggcaga ccgtgcacga ttggttatga tttatcagaa acagaggact ttacagccgc gtgtgctact 1471 tttgcgttag ataatggtaa agttgcagtt ttatcgcatt catggattcc taagcacaaa gttgaatatt 1541 ctaacgaaaa aataccctat agagaatggg aagaagatgg cttattaaca gtgcaagata agccttatat 1611 tgactaccaa gatgttttaa attggataat taagatgaat gagcattatg tagtagaaaa aattacttat 1681 gatagagcga acgcattcaa actaaatcaa gagttaaaaa attacgggtt tgaaacggaa gaaacaagac 1751 aaggagcttt gaccttgagc cctgcattga aggatttaaa agaaatgttt ttagatggga aaataatatt 1821 taataataat cctttaatga aatggtatat caataetgtt cagttgaaac tagacagaaa cggaaactgg 1891 ttgccgtcta agcaaagcag atatcgtaaa atagatggct ttgcagcatt tttaaacaca tatacagata 1961 ttatgaataa agttgtttct gatagtggtg aaggaaacat agagtttatt agtattaaag acataatgcg 2031 ttaaggaggt gaatgttatc gcaaaagaga atattgtcac acgcataaag aaaaaattga tagacaattg 2101 gattgatcag tcaacttcta agctttatga ctttagccca tggaaaaata gatctttttg gggtgtaatt 2171 aataatacgc ttgaaactaa tgaaacgata ttttcagcta ttacaaagtt atctaattcg atggctagtt 2241 tgcccttgaa aatgtatgaa gattataaag tagttaatac agaagtatct gatttactta cagtgtcacc 2311 gaataattct ctgagcagtt ttgattttat taatcaaatt gaaacaatca gaaatgaaaa aggtaatgca 2381 tatgtgctaa ttgaacgaga catctatcat caaccatcaa agcttttctt attaaatcca gatgttgttg 2451 aaatgttaat tgaaaaccaa tcacgtgaac tttattattc cattcatgct gcaactggaa ataaattgat 2521 tgttcataat atggacatgt tgcattttaa acacatcgtg gcatctaata tggtgcaagg cattagtccg 2591 attgatgtgt tgaagaatac aactgatttt gataatgcag taagaacctt taatcttaca gaaatgcaaa 2661 aacctgattc tttcatgctt aaatatggtt ccaatgtagg taaagaaaaa aggcagcaag tgttagaaga 2731 tttcaaacag tactatgaag aaaacggtgg aatattattc caagagcctg gtgttgaaat cgaaccgtta 2801 cctaaaaaat atgtctccga agatatagtg gcaagcgaga atttaacaag agaaagagta gctaacgttt 2871 ttcaattgcc ctcagtattc ttaaatgcaa gatcaaatac aaatttcgcg aaaaatgaag agttaaacag 2941 attttacttg cagcatacct tattgccaat cgtcaaacag tatgaagaag aatttaatcg gaaactactt 3011 actaaaacag acagagaaaa aaataggtat tttaaattta acgttaaatc ttatttaagg gctgatagtg 3081 caacacaagc agaagtgtac tttaaagcag ttcgtagtgg ttactacact ataaatgaca ttagagagtg 3151 ggaagattta ccaccagttg aaggtggaga taagccgcta ataagcggtg atttataccc aattgacacg 3221 ccacttgaat taagaaaatc tttgaaaggt ggtgataaaa atgtcaatga aagctaagta ttttcaaatg 3291 aaaagaaaat caaaaagtaa aggtgaaate tttatttatg gtgatattgt aagtgataaa tggtttgaaa 3361 gtgatgtaac tgctacagat ttcaaaaata aactagatga actaggagac atcagtgaaa tagatgttca 3431 tataaattca tctggaggca gtgtatttga agggcatgca atatacaata tgctaaaaat gcatcctgca 3501 aaaattaata tctatgtcga tgccttagcg gcatcaattg ctegtgttat cgctatgagt ggtgacacta 3571 tttttatgca caaaaatagt tttttaatga ttcataattc atgggttatg actgtaggta atgcagaaga 3641 gttaagaaag acagcggatt tacttgaaaa aacagatgct gttagtaatt cagcttattt agataaagca 3711 aaagatttag atcaagaaca cttaaaacag atgttagatg cagaaacttg gcttactgca gaagaagcct 3781 tgtctttcgg cttgatagat gaaattttag gagctaatga aataactgct agtatctcta aagagcaata 3851 taagcgtttc gagaacgtcc cagaagattt aaagaaagat gtagacaaaa tcactaaaat cgatgatgta 3921 gatacgtttg aattggttga aacacctaaa gaaagtatgt cactagaaga aaaagaaaaa agagaaaaaa 3991 ttaaacgcga atgcgaaatt ttaaaaatga caatgagtta ttaggaggaa atgaaatgcc gacattatat 4061 gaattaaaac aatccttagg tatgattgga caacaattaa aaaataaaaa tgatgaattg agtcagaaag 4131 caacagaccc aaatattgat atggaagaca tcaaacaact agaaacagaa aaagcaggct tacaacaaag 4201 atttaacatt gttgaaagac aagtaaaaga cattgaagaa aagaaaaag cgaaagttaa agacacagga 4271 gaagcttatc aatctttaaa tgatcatgag aagatggtta aagctaaggc agagttttat cgtcacgcga 4341 ttttaccaaa tgaatttgaa aaaccttcaa tggaggcaca acgtttatta cacgctttac caacaggtaa 4411 tgattcaggt ggtgataagc tcttaccaaa aacactttct aaagaaattg tttcagaacc atttgctaaa 4481 aaccaattac gtgaaaaagc tcgtctaact aacattaaag gtttagagat tccaagagtt tcatatactt 4551 tagacgatga tgacttcatt acagatgtag aaacagcaaa agaattaaaa ttaaaaggtg atacagttaa 4621 attcactact aataaattca aagtatttgc tgcaatttca gatactgtaa ttcatggatc agatgtagat 4691 ttagtaaact gggttgaaaa cgcactacaa tcaggtctag cagctaaaga acgtaaagat gccttagcag WO 00/32825 PCT/IB99/02040 176 4761 taagtcctaa atctggatta gatcacatgt cattttacaa tggatctgtt aaagaagttg agggagcaga 4831 catgtatgat gctattatta acgctttagc agatttacat gaagattacc gtgataacgc aacaatttat 4901 atgcgatatg cggattatgt caaaattatt agtgttcttt caaatggaac aacaaatttc tttgacacac 4971 cagcagaaaa agtatttggc aaaccagtag tatttacaga tgcagcagtt aaacctattg tgggagattt 5041 caattatttt ggaattaact atgatggaac aacttatgac actgataaag atgttaaaaa aggcgaatat 5111 ttgtttgtat taactgcatg gtatgatCag caacgtacat tagacagtgc attcagaatt gcaaaagcaa 5181 aagaaaatac aggttcatta cccagctaag ccccaaaagg ttaatgtaac agctaaggct aaatcagctg 5251 taatatcagc cgaatagggg tgatgaaatg agtttagaag aaattaaatt gtggttgaga attgactata 5321 atttcgaaaa tgatttaatt gaaggtCtca ttcaatcggc taagtctgaa ttactattaa gtggggttcc 5391 agattatgac aaagatgaCt tggaataCCC gcttttttgt acagcgatta gatatatcat tgcaagagat 5461 tatgaaagtc gtgggtactc aaatgaccaa tctagaagca aggtttttaa tgaaaaggga ttgcaaaaaa 5531 tgattctgaa attaaaaaag tggtaggtga tttttaaatg gaatttaatg aatttaaaga tcgcgcatat 5601 ttttttcaat atgtaaataa agggccgtat ccagatgaag aggaaaaaat gaagttgtat agttgctttt 5671 gtaaaatata taatccttct atgaaagata gagaaatttt aaaagcgact gaatcaaagt caggactaac 5741 cataattatg aggtcttcta aaattgaata tctaccacaa acaaatcact tagttaaaat tgacagaggc 5811 ttatattccg ataaattatt caacattaaa gaaataagaa ttgatacacc agatattggc tataatacag 5881 tggttttatc agaaaaatga gtgtagaaat taaagggata cctgaagtgt tgaagaaatt agaatcggta 5951 tacggtaaac aatcaatgca agctaagagt gatagagctt taaatgaagc atctgaattt tttataaagg 6021 ctttaaagaa agaattcgag agttttaaag atacgggtgc tagcatagaa gaaatgacta aatctaagcc 6091 ttatacaaaa gtaggaagtc aagaaagagc tgttttaatt gaatgggtag gccctatgaa tcgcaaaaac 6161 attattcact tgaatgaaca tggttataca agagatggaa aaaaatatac accaagaggt tttggagtta 6231 ttgcaaaaac attagctgct aatgaacgga agtatagaga aattataaaa aaggagttgg ccagataaat 6301 gaatatatta aacaccataa aagaaatttt attatctgat gcagagctcc aaacatatat aaattctaga 6371 atatactatt ataaagtcac tgaaaatgct gaaacttcca aaccttttgt tgttattaca cctatttatg 6441 atttaccttc agacttcatg tctgataaat atcttagtga agaatactta attcaaatag atgtagaatc 6511 ttcaaataat cagaaaacaa ttgatataac aaaacgaata agatatctgt tatatcaaca aaatttaatt 6581 caagcatcta gtcagttaga tgcttatttt gaagaaacta aacgttatgt gatgtcgaga cgttatcaag 6651 gcataccaaa aaatatatat tataaaaatc agcgcatcga ataggtgtgc tttttaattt ttaaggagga 6721 aataagcaat ggcagaagga caaggttctt ataaagtagg ttttaaaaga ttatacgttg gagtttttaa 6791 cccagaagca acaaaagtag ttaaacgcat gacatgggaa gatgaaaaag gtggtacagt tgatctaaat 6861 atcacaggtt tagcaccaga tttagtagat atgtttgcat ctaacaaacg tgtttggatg aaaaaacaag 6931 gtactaatga agttaagtct gacatgagta tttttaatat tccaagtgaa gatcaaata cagttattgg 7001 tcgttctaaa gataaaaatg gtacatcttg ggtaggagag aatacaagag caccatacgt aacagttatt 7071 ggagaatctg aagatggttt aacaggtcaa ccagtgtacg ttgcgctact taaaggtact tttagcttgg 7141 attcaattga atttaaaaca cgaggagaaa aagcagaagc accagagcca acaaaattaa ctggtgactg 7211 gatgaacaga aaagttgatg ttgatggtac tccacaaggt attgtatacg ggtatcatga aggtaaagaa 7281 ggagaagcag aattcttCaa aaaagtattc gttggataca cggacagtga agatcattca gaggattctg 7351 caagttcgtt acccagctaa cccccaaaat gttgaagtag cagttaattc aaaatctgca acagtttcag 7421 cagaataggg gctttcaaaa taaatcaaag gagaataatt tatgactaaa actttaaagg tttataaagg 7491 agacgacgtc gtagcttctg aacaaggtga aggcaaagtg tcagtaactt tatctaattt agaagcggat 7561 acaacttatc caaaaggtac ttaccaagtg gcatgggaag aaaatggtaa agaatctagt aaagttgatg 7631 tacctcaatt caaaaccaat ccaattctag tctcaggcgt atcatttaca cccgaaacta aatcaatcac 7701 ggtaaatgct gatgacaatg ttgaaccaaa cattgcacca agtacagcaa cgaataaaac gttgaaatat 7771 acaagtgaac atccagagtt tgttactgtt gatgagagaa caggagcaat tcacggtgta gctgagggaa 7841 cttcagttat cactgctacg tctactgacg gaagtgacaa gtctggacaa attacagtaa cagtaacaaa 7911 tggataatta tttgagacgc agaatatctg cgtctttttt atttgaataa aaggagctaa tacaatgatt 7981 aaatttgaaa ttaaagaccg taaaacagga aaaacagaga gctatacaaa agaagatgtg acaatgggcg 8051 aagcagaaaa atgctatgag tatttagaat tagtaaatca agagaataaa aaagaagtac ctaacgcaac 8121 aaaaatgaga caaaaagagc gacagttatt agtagattta tttaaagatg aaggattgac tgaagaagat 8191 gttttgaaca agatgagcac taaaacttat acaaaagcct tgaaagatat atttcgagaa atcaatggtg 8261 aagatgaaga agattcagaa actgaaccag aagagatggg aaagacagaa gaacaatctc aataaaagat 8331 attttatcga acattaagaa aatacaacgt ttctgtatgg agcagtatgg gtggacatta actgaagtca 8401 gaaaacagcc gtatgtaaaa cttttagaaa tacttaatga agagaataaa gaagagactg aagaaaaaca 8471 aagtgaacaa aaagtcatta caggtacgga tttaagaaaa ctttttggaa gctagaaagg aggttaatat 8541 gaatgaaaaa gtagaaggca tgaccttgga gctgaaatta gaccatttag gtgtccaaga aggcatgaag 8611 ggtttaaagc gacaattagg tgttgttaat agtgaaatga aagctaatct gtcatcattt gataagtctg 8681 aaaaatcaat ggaaaagtat caggcgagaa ttaaggggtt aaatgataag cttaaagttc aaaaaaagat 8751 gtattctcaa gtagaagatg agcttaaaca agttaacgct aattatcaaa aagctaaatc tagtgtaaaa 8821 gatgttgaga aagcatattt aaagctagta gaagctaata aaaaagaaaa attagctctt gataaatcta 8891 aagaagcctt aaaatcttcg aatacagaac ttaaaaaagc tgaaaatcaa tataaacgta caaatcaacg 8961 taaacaagat gcatatcaaa aacttaaaca gttgagagat gcagaacaaa agcttaagaa tagtaaccaa 9031 gctactactg cacaactaaa aagagcaagt gacgcagtac agaagcagtc cgctaagcat aaagcacttg 9101 ttgaacaata taaacaagaa ggcaatcaag ttcaaaaact aaaagtacaa aatgataatc tttcaaaatc 9171 aaacgaaaaa atagaaaatt cttacgctaa aactaatact aaattaaagc aaacagaaaa agaatttaat 9241 gatttaaata atactattaa gaatcatagc gctaatgtcg caaaagctga aacagctgtt aacaaagaaa 9311 aagctgcttt aaataattta gagcgttcaa tagataaagc ttcatccgaa atgaagactt ttaacaaaga 9381 acaaatgata gctcaaagtc atttcggcaa acttgctagt caagcggatg tcatgtcaaa gaaatttagt 9451 tctattggag ataaaatgac ttccctagga cgtacgatga cgatgggcgt atctacaccg attactttag 9521 ggttaggtgc agcattaaaa acaagtgcag acttcgaagg gcaaatgtct cgagttggag cgattgcaca 9591 agcaagcagt aaagacttaa aaagcatgtc taatcaagcg gttgacttag gcgctaaaac aagtaaaagt 9661 gctaacgaag ttgctaaagg tatggaagaa ttggcagctt taggctttaa tgccaaacaa acaatggagg 9731 ctatgccggg tggtatcagt gcagcagaag caagcggtgc agaaatggct acaactgcaa ctgtaatggc 9801 atcagcaatt aattctttcg gtttaaaagc atctgatgca aaccatgttg ctgatttact tgcgagatca 9871 gctaatgata gtgctgcaga tattcaatac atgggagatg cattaaaata tgcaggtact ccagcaaaag 9941 cattaggagt ttcaatagag gacacttctg cagcaattga agttttatct aactcagggt tagaggggtc 10011 tcaagcaggt actgcattaa gagcttcgtt tattaggcta gctaatccaa gtaaaagtac agctaaggaa WO 00/32825 PCT/IB99/02040 177 10081 atgaaaaaat taggtattca tttgtctgat gctaaaggtc aatttgttgg catgggtgaa ttgattagac 10151 agttccaaga caacatgaaa ggcatgacga gagaacaaaa actagcaaca gtggctacaa tagttggcac 10221 tgaagcagca agtggatttt tagccttgat tgaagcgggt ccagataaaa ttaatageta tagcaaatca 10291 ttgaagaact ctaatggtga aagtaaaaaa gcagctgatt tgatgaaaga caacctcaaa ggtgctctgg 10361 aacaattagg tggcgctttt gaatcgttag caattgaagt tggtaaagat ttaacgccta tgattagagc 10431 aggtgcggaa ggattaacaa aattagttga tggatttaca catcttcctg gttggtttag aaaggcttcg 10501 gtaggtttag cgatttttgg tgcatctatt ggccctgctg ttcttgctgg tggcttatta atacgtgcag 10571 ttggaagcgc ggctaaaggc tatgcatcat taaatagacg cattgctgaa aatacaatac tgtctaatac 10641 caattcaaaa gcaatgaaat ctttaggtct tcaaacctta tttcttggtt ctacaacagg aaaaacgtca 10711 aaaggcttta aaggattagc cggagctatg ttgtttaatt taaaacctat aaatgttttg aaaaattctg 10781 caaagctagc aattttaccg ttcaaacttt tgaaaaacgg tttaggatta gccgcaaaat ccttatttgc 10851 agtaagtgga ggcgcaagat ttgctggtgt agccttaaag tttttaacag gacctatagg tgctacaata 10921 actgctatta caattgcata taaagttttt aaaaccgcat atgatcgtgt ggaatggttc agaaacggta 10991 ttaacggttt aggagaaact ataaagtttt ttggtggcaa aattattggc ggtgctgtta ggaagctagg 11061 agagtttaaa aattatcttg gaagtatagg caaaagcttc aaagaaaagt tttcaaagga tatgaaagat 11131 ggttataaat ctttgagtga cgatgacctt ctgaaagtag gagtcaacaa gtttaaagga tttatgcaaa 11201 ccatgggcac agcttctaaa aaagcatctg atactgtaaa agtgttgggg aaaggtgttt caaaagaaac 11271 agaaaaagct ttagaaaaat acgtacacta ttctgaagag aacaacagaa tcatggaaaa agtacgttta 11341 aactcgggtc aaataacaga agacaaagca aaaaaacttt tgaaaattga agcggattta tctaataacc 11411 ttatagctga aatagaaaaa agaaataaaa aggaactcga aaaaactcaa gaacttattg ataagtatag 11481 tgcgttcgat gaacaagaaa agcaaaacat tttaactaga actaaagaaa aaaatgactt gcgaattaaa 11551 aaagagcaag aactcaatca gaaaatcaaa gaattgaaag aaaaagcttt aagtgatggt cagatttcag 11621 aaaatgaaag aaaagaaatt gaaaagcttg aaaatcaaag acgtgacatc actgttaaag aattgagtaa 11691 gactgaaaaa gagcaagagc gtattttagt aagaatgcaa agaaacagaa atgcttattc aatagacgaa 11761 gcgagcaaag caattaaaga agcagaaaaa gcaagaaaag caagaaaaaa agaagtggac aagcaatatg 11831 aagatgatgt cattgctata aaaaataacg tcaacctttc taagtctgaa aaagataaat tattagctat 11901 tgctgatcaa agacataagg atgaagtaag aaaggcaaaa tctaaaaaag atgctgtagt agacgttgtt 11971 aaaaagcaaa ataaagatat tgataaagag atggatttat ccagtggtcg tgtatataaa aatactgaaa 12041 agtggtggaa tggccttaaa agttggtggt ctaacttcag agaagaccaa aagaagaaaa gtgataagta 12111 cgctaaagaa caagaagaaa cagctcgtag aaacagagaa aatataaaga aatggtttgg aaatgcttgg 12181 gacggcgtaa aaactaaaac tggcgaagct tttagtaaaa tgggcagaaa tgctaatcai tttggcggcg 12251 aaatgaaaaa aatgtggagt ggaatcaaag gaattccaag caaattaagt tcaggttgga gctcagccaa 12321 aagttctgta ggatatcaca ctaaggctat agctaatagt actggtaaat ggtttggaaa agcttggcaa 12391 tctgttaaat cgactacagg aagtatttac aatcaaacta agcaaaagta ttcagatgcc tcagataaag 12461 cttgggcgca ttcaaaatct atttggaaag ggacatcaaa atggtttagc aatgcatata aaagtgcaaa 12531 gggctggcta acggatatgg ctaataaatc gcgctcgaaa tgggataata tttctagtac agcatggtcg 12601 aatgcaaaat ccgtttggaa aggaacatcg aaatggttta gtaactcata caaatcttta aaaggttgga 12671 ctggagatat gtattcaaga gcccacgatc gttttgatgc aatttcaagt tcggcatggt ctaacgctaa 12741 atcagtattt aatggtttta gaaaatggct atcaagaaca tatgaatgga ttagagatat tggtaaagac 12811 atgggaagag ctgcggctga tttaggtaaa aatgttgcta ataaagctat tggcggttta aatagcatga 12881 ttggcggtat taataaaata tctaaagcca ttactgataa aaatctcatc aagccaatac ctacattgtc 12951 tactggtact ttagcaggaa agggtgtagc taccgataat tcgggagcat taacgcaacc gacatttgct 13021 gtattaaatg atagaggttc tggaaacgcc ccaggtggtg gagttcaaga agtaattcac agggctgacg 13091 gaacattcca tgcaccccaa ggacgagatg tggttgttcc actaggagtt ggagatagtg taataaatgc 13161 caatgacact ctgaagttac agcggatggg tgttttgcca aaattccatg gtggtacgaa aaagaaagat 13231 tggctagacc aacttaaagg taatataggt aaaaaagcag gagaatttgg agctacagct aaaaacacag 13301 cgcataatat caaaaaaggt gcagaagaaa tggttgaagc agcaggcgat aaaatcaaag atggtgcatc 13371 ttggttaggc gataaaatcg gcgatgtgtg ggattacgta caacatccag ggaaactagt aaataaagta 13441 atgtcaggtt taaatattaa ttttggaggc ggactaacgc tacagtaaaa attgctaaag gcgcgtactc 13511 attgctcaaa aagaaattaa tagacaaagt aaaatcgtgg tttgaagatt ttggtggtgg aggcgatgga 13581 agctatctat ttgaatatcc aatctggcaa agatttggac gctacacagg tggacttaac tttaatgacg 13651 gtcgtcacta tggtatagac tttggtatgc ctactggaac aaacgtttat gccgttaaag gtggtatagc 13721 agataaggta tggactgatt acggtggcgg taattctata caaattaaga ccggtgctaa cgaatggaac 13791 tggtatatgc atttatctaa gcaattagca agacaaggcc aacgtattaa agctggtcaa ctgataggga 13861 aatcaggtgc tacaggtaat ttcgttagag gagcacactt acatttccaa ttgatgcaag ggtcacatcc 13931 agggaatgat acagctaaag atccagaaaa atggttgaag tcacttaaag gtagtggcgt tcgaagtggt 14001 tcaggtgtta ataaggctgc atctgcttgg gcaggcgata tacgtcgtgc agcaaaacga atgggtgtta 14071 atgttacttc gggtgatgta ggaaatatca ttagcttgat tcaacacgaa tcagaggaa atgcaggtat 14141 aactcaatct agttcgctta gagacatcaa cgttttacag ggcaatccag caaaaggatt gcttcaatat 14211 atcccacaaa catttagaca ttatgctgtt agaggtcaca acaatatata tagtggttac gatcagttat 14281 tagcgttctt taacaacaga tattggcgct cacagtttaa cccaagaggt ggttggtctc caagtggtcc 14351 aagaagatat gcgaatggtg gtttgattac aaagcatcaa cttgctgaag tgggtgaagg agataaacag 14421 gagatggtta tccctttaac tagacgtaaa cgagcaattc aattaactga acaggttatg cgcatcatcg 14491 gtatggatgg caagccaaat aacatcactg taaataatga tacttctaca gttgaaaaat tgttgaaaca 14561 aattgttatg ttaagtgata aaggaaataa attaacagat gcattgattc aaactgtttc ttctcaggat 14631 aataacttag gttctaatga tgcaattaga ggtttagaaa aaatattgtc aaaacaaagt gggcatagag 14701 caaatgcaaa taattatatg ggaggtttga ctaattaatg caatcttttg taaaaatcat agatggttac 14771 aaggaagaag taataacaga ttttaatcag cttatatttt tagatgcaag ggctgaaagt ccaaacacca 14841 atgataacag tgtaactatt aacggagtag atggtatttt accgggcgca attagttttg cgccttttac 14911 attagtatta aggtttggct atgatggtat agatgttata gatttaaatt tatttgagca ttggtttaga 14981 tctgtgttta atcgcagaca tccttattat gttattactt ctcaaatgcc tggtgttaaa tatgcagtga 15051 atacagctaa tgttacatct aatttaaaag atggttcttc aactgaaatt gaagtaagtt taaatgttta 15121 taaagggtat tctgaatcag ttaattggac cgatagcgag ttcttattcg actctaattg gatgtttgaa 15191 aatggaattc ctcttgattt cacacctaaa tatactcata catcaaatca atttactatt tggaacggtt 15261 ctactgatac gataaatcca cgattcaagc acgatttgaa aatattaatt aatttaaatg cgagtggagg 15331 atttgaactg gttaactata caacaggtga tatttttaag tacaacaaaa gtatagataa aaacactgat WO 00/32825 PCT/IB99/02040 178 15401 tttgttttag atggtgtgta tgcatatcga gatataaata gagtgggaat tgatacaaat agaggcatta 15471 taacattagc gccaggtaaa aatgaattta agattaaagg agacatcagt gatattaaaa ctacatttaa 15541 gtttcctttt atttataggt aggtgattta atggattatc atgatcattt atcagtaatg gattttaatg 15611 aattgatttg tgaaaattta ctagatgtag attatggttc ttttaaagaa tattatgaac tgaatgaagc 15681 taggtacatc acttttacag tttatagaac tactcataat agttttgttt tcgatttact aatttgtgaa 15751 aacttcataa tttatcatgg tgaaaaatac acaattaagc agacagcgcc aaaggttgaa ggtgataaag 15821 tttttattga agttacggca tatcacataa tgtatgaatt tcaaaatcac tcagtggaat caaataagct 15891 tgatgacgac agtagcgaaa ctggtaaaac gccagaatac tctttagatg agtacttaag atatggattt 15961 gcaaatcaaa aaacttcggt caaaatgacc tataaaataa ttggaaattt taagcgaaaa gtaccgattg 16031 acgaattagg taacaaaaac ggcttagaat actgtaaaga agcggtagac ctatttggct gtataattta 16101 cccaaatgat acggagatat gtttttattc tcctgaaaca ttttatcaaa gaagcgagaa agtgattcga 16171 tatcaatata atactgatac tgtatctgca actgtcagta cattggaatt aagaacagct ataaaagttt 16241 ttggaaaaaa gtatacagct gaggaaaaga aaaattataa tcctattaga acaactgaca ttaaatattc 16311 aaatggtttt ataaaagaag gtaCttatcg taccgcaaca attgggtcta aagctactat taactttgat 16381 tgcaagtatg gtaatgaaac agttagattt acaataaaaa agggctctca aggtggaata tataagttga 16451 ttttagacgg caagcaaatt aagcaaattt cttgttttgc taagtcggtt cagtctgaaa caatagattt 16521 aataaaaaat attgataaag gcaagcacgt tttagaaatg atatttttag gagaagaccc caaaaataga 16591 attgatatat cttcaaataa aaaagctaag ccttgtatgt atgttggaac tgaaaaatca acagtCttaa 16661 atttaattgc tgacaactca ggtcgcaatc aatacaaagc aattgttgac tacgtcgcag atagtgcaaa 16731 gcagtttggg attcgatatg ctaatacgca aacaaatgaa gatatcgaaa cacaggataa gctgttagaa 16801 tttgcaaaaa agcaaataaa tgatactcct aagactgaat tagatgttaa ttatataggt tatgaaaaaa 16871 tagagccaag agatagcgta ttctttgttc atgaattaat gggatataac actgaattaa aggttgttaa 16941 acttgatagg tcacatccat ttgtaaacgc aatagatgaa gtgtctttca gcaatgaaat aaaggatatg 17011 gtacaaattc aacaagcgct taacagacga gttattgcac aagataatag atataaCtat caagcaaatc 17081 gtataaatca tttatacact agtactttga attctccttt cgagacaatg gatataggga gtgtattaat 17151 ataatggcaa cagaagaagt taaaatcaaa gcgctacttg aaaacgataa acagtacttt ccagctacac 17221 attggaaagc tataaatggg ataccttatg caggcagtag tgatattgat ggattgcctc aagacggtat 17291 catttcggta gatgataaaa ataaattaga taatttaaaa ataggcgaag caggaattat tcaaaatagc 17361 attgtacaga aatccccaaa cggtaaattg tggaaaataa cagttgacga tagtgggaaa cttggtacag 17431 tgctatttta ttagaaagga aggtgcatta tggaaaattt gtatttaata aaggatttgg gagctttagc 17501 aggtcgagat tatagagcta aggaaataca aaacttacaa agaatagagc aatttgcgct tggcttgaca 17571 acagagttta agttgcatca gaaagctaaa acaattcaac acttcgctga gcaaatttat tataatggta 17641 gatcgcaagc agcagtaaac aaatctttac aaagtcaaat taacgcactt gttgtggcac cacgtaataa 17711 cagtgctaat gagattgttc aagctcgagt taatgtaaac ggcgaaacct ttgacacatt aaaagaacat 17781 ttagacgatt gggaaaccca aactcaaatt aataaagagg aaactataag agaattaaat aagaccaaac 17851 aagaaattct tgatatcgag tatcgttttg aacctgataa gcaagaattt ttatttgtga cagaacttgc 17921 acctcttaca aatgcagtaa tgcaatcctt ctggtttgat aatagaacag gcatagtata catgacacaa 17991 gctagaaata atggctatat gctaagtcgt ctaagaccta atggtcaatt tatagacagc tcattgattg 18061 taggtggggg tcatggtaca cataacggtt atagatatat tgatgatgag ttatggattt atagttttat 18131 cttaaatggt aataatgaga atacattagt tcgtttcaag tatacgccta atgtggaaat tagctatggc 18201 aagtatggta tgcaagatgt atttacagga cacccagaaa aaccctacat cacccctgtc ataaatgaaa 18271 aagaaaataa aattctatac agaattgaga gacctagaag tcactgggaa cttgaaaact caatgaatta 18341 tatagagata agaagtttag acgatgttga taaaaatatt gataaagttt tgcataaaat cagtatccct 18411 atgagactaa caaacgaaac ccaaccaatg cagggtgtga cttttgatga aaaatacttg tattggtata 18481 caggagacag taatccaaat aatagaaact atttaacggc tttcgattta gaaacaggag aagaagcgta 18551 tcaggttaat gctgactatg gtggaacact agattcattt cctggcgaat ttgcggaagc agaaggtttg 18621 caaatatact atgacaaaga tagtggtaaa aaagctttga tgctaggtgt tactgtcggt ggtgatggaa 18691 atagaacaca tcgtattttc atgattgggc aaagaggtat tttagaaata cttcactcaa gaggcgttcc 18761 ttttatcatg agtgacacag gtggtagagt taaaccttta ccaatgaggc ctgataaact taagaatctt 18831 gggatgttaa cagagccagg tctttactat ttatacactg atcatacagt tcaaatcgat gatttcccat 18901 taccaagaga atggcgtgat gcaggttggt tcttggaagt taagccacca caaactggcg gtgatgtaat 18971 tcagatattg acgcgtaata gttatgcaag gaatatgatg acttttgaaa gggtgctttc tggaagaact 19041 ggagacattt cggactggaa ttatgtgcct aaaaatagtg gtaaatggga gagagtacct tcattcatca 19111 caaaaatgtc agatattaac atagtaggca tgtcgtttta tttaactacg gatgatacaa aacgttttac 19181 agattttcca actgaacgta aaggggtagc tggttggaac ttatatgtag aagcttcaaa cacaggtggc 19251 tttgttcata ggctagttcg taatagtgtt acagcatctg ctgagatact attgaaaaat tatgatagta 19321 aaacaagttc agggccatgg actttacacg aagggagaat tataagttaa tgagtaattt agagaaatct 19391 gtagctataa atttagaaaa cacagcgcat tatgaaaata tttcaaatct agatataact tttagaacag 19461 gagagagtga ttcttctgtt cttcttttta atatcactaa aaataatcaa ccgttattat tgagtgaaga 19531 aaatatcaaa gcacgaatag cgattcgagg taaaggagtc atggtagttg ctccactaga aatattagat 19601 ccatttaaag gtattttaaa atttcaatta cctaatgatg taattaaacg agatggaagt tatcaagctc 19671 aagtttcggt tgcagaatta ggtaattcag acgtggtagt tgtcgagaga actatcacat ttaacgttga 19741 aaaaagtttg tttagcatga ttccatctga aacaaaatta cactatattg ttgaatttca ggaattagaa 19811 aaaactatta tggatcgtgc gaaagcaatg gacgaggcta taaaaaatgg tgaagattat gcgagtctga 19881 ttgaaaaagc taaagaaaaa ggtctatcag atattcaaat agcaaaatct tcaagtatag atgaattaaa 19951 gcaacttgct aatagccata tatctgattt ggaaaataaa gcgcaagcat attcaagaac attcgatgag 20021 caaaagcgat atatggatga gaaacatgaa gccttcaagc agtcagtgaa tagtggtggt ttagtcacaa 20091 gtggttctac ttcaaattgg caaaaagcta agattactaa agatgatggt aagataatgc agattactgg 20161 atttgatttt aataatccag aacaaagaat aggtgattca acccaattta tttatgtttc gcaagctata 20231 aattatccaa gaggtgttag tactaacggt actgtcgaat atttagtagt aacttcagat tacaagcgta 20301 tgacttatcg accgaacggt acaaataaag tgtttgttaa aagaaaagaa gcgggttcat ggtctgagtg 20371 gtcagaatta gctattaatg attacaatac accttttgaa actgttcaaa gtgccaatc aaaagctaat 20441 atggccgaaa gtaacgctaa attatacgca gatgacaagt ttaataaaag gtattcggtt atttttgatg 20511 gaacagcaaa tggtgtgggc tctacattgt acttaaatga gagtttagac caatttattt tattaatttt 20581 ttatgggact tttccaggtg gtgactttac agagtttggc agtccttttg gaggaggaaa gatttcattg 20651 aatccctcaa atcttccaga tggtgatgga aatggtggag gtgtttatga gtttggatta actaaatcta WO 00/32825 PCT/IB99/02040 179 20721 gtcgtacatc tttaactata tcaaacgatg tctatttcga cttaggaagt caaagaggct ctggtgcgaa 20791 cgcaaataga gggacaatta acaaaattat aggagtgaga aaataatgca aatattagtt aacaagcgta 20861 atgagataat ttcatacgct atcattggtg gctttgaaga aggtattgat attgaaaatt taccagaaaa 20931 tttctctcaa gtttttagac ctaaagcctt taaatattca aatggggaaa tagtttttaa cgaagattat 21001 tcagaagaaa aagatgactt gcatcaacag attgacagtg aagaacaaaa cacagtcgct tctgatgaca 21071 tcttacgaaa aatggttgct agtatgcaga aacaagttgt tcaaagtaca aagttatcga tgcaagttaa 21141 taagcaaaat gcactaatgg caaaacaact tgtgacactt aataaaaaat tagaagaggt taaaggagag 21211 actgaaaatg cttaaattaa tttcaccaac attcgaagat attaaaacat ggtatcaatt gaaagaatat 21281 agtaaagaag atatagcgtg gtatgtagat atggaagtta tagataaaga ggaatatgca attattacag 21351 gagaaaagta tccagaaaat ctagagtcat aggttataat cttatggctt tttaatttga ataaagtggg 21421 tggtgtaatg tttggattta ccaaacgaca cgaacaagat tggcgtttaa cgcgattaga agaaaatgat 21491 aagactatgt ttgaaaaatt cgacagaata gaagacagtc tgagaacgca agaaaaaatt tatgacaagt 21561 tagatagaaa tttcgaagaa ctaaggcgtg acaaagaaga agatgaaaaa aataaagaga aaaatgctaa 21631 aaatattaga gacatcaaga tgtggattct aggattaata gggacgattc taagtacatt tgttatagcc 21701 ttgttaaaaa ctatttttgg catttaaagg aggtgattac catgcttaag ggaattttag gatatagctt 21771 ttggtcgtgt ttctggttta gtaagtgtaa gtaatagtta agagtcagtg cttcggcact ggctttttat 21841 tttggaaaaa aggagcaaac aaatggatgc aaaagtaata acaagataca tcgtattgat cttagcatta 21911 gtaaatcaat tcttagcgaa caaaggtatt agcccgattc cagtagacga tgagaatata tcatcaataa 21981 tacttactgt tgttgcttta tatactacgt ataaagacaa tccaacatct caagaaggta aatgggcaaa 22051 tcaaaagcta aagaaatata aagctgaaaa caagtataga aaagcaacag ggcaagcgcc aattaaagaa 22121 gtaatgacac ctacgaatat gaacgacaca aatgatttag ggtaggtgtt gaccaatgtt gataacaaaa 22191 aaccaagcag aaaaatggtt tgataattca ttagggaagc agttcaatcc tgatttgttt tatggatttc 22261 agtgttacga ttacgcaaat atgtttttta tgatagcaac aggcgaaagg ttacaaggtt tatacgctta 22331 taatattcca tttgataata aagcaaggat tgaaaaatac gggcaaataa ttaaaaacta tgatagcttt 22401 ttaccgcaaa agttggacat tgtcgttttc ccgtcaaagt atggtggcgg agctggacat gttgaaattg 22471 ttgagagcgc taatCtaaaC actttcacat cgtttggcca aaattggaat qgtaaaggtt ggacaaatgg 22541 cgttgcgcaa cctggttggg gtcccgaaac cgttacaaga catgttcatt attacgatga cccaatgtat 22611 tttattagat taaatttccc agataaagta agtgttggag ataaagctaa aagcgttatt aagcaagcaa 22681 ctgccaaaaa gcaagcagta attaaaccta aaaaaattat gcttgtagcc ggtcatggtt ataacgatcc 22751 tggagcagta ggaaacggaa caaacgaacg cgattttata cgtaaatata taacgccaaa tatcgctaag 22821 tatttaagac atgccggtca tgaagtcgca ttatatggtg gctcaagtca atcacaagac atgtatcaag 22891 atacagcata cggtgttaat gtaggtaata aaaaagatta tggcttatat tgggttaaat cacaggggta 22961 tgacattgtt ctagaaatac atttagacgc agcaggagaa agcgcaagtg gtgggcatgt tattatctca 23031 agtcaattca atgcagatac tattgataaa agtatacaag atgttattaa aaataactta ggacaaataa 23101 gaggtgtaac acctcgtaac gatttactaa atgttaacgt atcagcagaa ataaatataa attatcgctt 23171 atctgaatta ggttttatca ctaataaaaa tgatatggat tggattaaga aaaactatga cttgtattct 23241 aaattaatag ccggtgcgat tcatggtaag cctatcggtg gtgtgatatc tagtgaggtt aaaacaccag 23311 ttaaaaacga aaagaatccg ccagtgccag caggttatac acccgataaa aataatgtac cgtataaaaa 23381 agaaactggt tattacacag ttgccaatgt taaaggtaat aacgtaaggg acggctattc aactaattca 23451 agaattactg gtgtattacc taataacgca acaatcaaat atgacggcgc atattgtatc aatggctata 23521 gatggattac ttatattgct aatagtggac aacgtcgtta tattgctaca ggagaggtag acaaggcagg 23591 taatagaata agcagttttg gtaagtttag tgcagtttga taattgtata tgatgaatct taggcaggta 23661 cttcggtact tgcctattat ttaaaattaa taaacagtta atttttacat gaatatatta aattttaaaa 23731 aaacaaacgt ttttagtata taaattattt tgtgttcgta ttgtgtgcta tgattaaaaa gttgttatgg 23801 tcaactatat cgtggtttta tgtttattat caatcaaaat ataaattatt tataatttgt ttggtaatga 23871 acgggttttt ttcgaaataa tagtaaaaaa acacatttgt agatattita aactcggtaa atcttttaat 23941 aaatatttaa ttttattaaa agttaaaaag gtttaatata aaaatgtaat aaaatttata aagaaaggaa 24011 atgattttta tggtcaaaaa aagactatta gctgcaacat tgtcgttagg aataatcact cctattgcta 24081 cttcgtttca tgaatctaaa gctgataaca atattgagaa tattggtgat ggcgctgagg tagtcaaaag 24151 aacagaagat acaagtagcg ataagtgggg ggtcacacaa aatattcagt ttgattttgt taaagataaa 24221 aagtataaca aagacgcttt gattttaaaa atgcaaggtt ttatcaattc aaagactact tattacaatt 24291 acaaaaacac agatcatata aaagcaatga ggtggccttt ccaatacaat attggtctca aaacaaatga 24361 ccccaatgta gatttaataa attatctacc taaaaataaa atagattcag taaatgttag tcaaacatta 24431 ggttataaca taggtggtaa ttttaatagt ggtccatcaa caggaggtaa tggttcattt aattattcaa 24501 aaacaattag ttataataaa ataaaaagta ggtgataaga tgactcaatt tctaggggcg cttcttctta 24571 caggagtttt aggttacata ccatataaat atctaacaat gataggttta gttagtgaaa aaaacaaggt 24641 tatcaatact cctgtattat tgattttttc tattgaaaca tgtttgatat ggttttatag ttttataatt 24711 tttaataatg ttgatttaaa aaatttgaat ttaattcagt tgcttacagg tctaaaagca aatattttgt 24781 ttctatttat ttttgtttta acagtgtttg tatttaatcc tttaattgtt aaatttatta tctggttaat 24851 taatataacc agaaagttta tgaaattgga ttgtataagc ttattagaca aaagagacaa gttgtttaat 24921 aacaacggta aaccagtatt tatagttata aaagactttg aaaacagaat cattgaagag ggtgaactta 24991 aaacctataa ttcagctggt agcgatttcg atttactaga agttgagcga caagatttca aagtatctga 25061 tttaccgtca aacgatgaat tgtatattaa acatacactt gtagacctta aacaacaaat taaattggat 25131 ttatatttaa tgaatgaata ctaatctttt ttcttagctt tttctgataa agtgcttttt aatttttcgc 25201 tggcgcccgg cttttcaaaa cttttgttta ttgggttact acgagtagct tcttgttttt tgtttttatc 25271 cgccataaaa ttctcaccac cattcaacgt ctacacttgt aggcgttttt ttatttagta aagtcataat 25341 gaatcttctt tggttaactt atctccatct attttttgtg aaataaattc caagtattta cgcgcattat 25411 gtgacgataa atctttaggt aactcataag tgaatggttg attaccacta gttaaaactt catatactat 25481 agtttctttt tttattttgc aattagttat tttcattata aacttccttt caaacactgc tgaaatagac 25551 gtcttttata ttaaagcgcc acacaggcgc tgttaatcac aatacaactt tgcccattac tttaatatta_ 25621 ctaaacgaag cgactttgat atcatcatac ttcggattta gagataccaa attaatatag tcttcgcata 25691 tatctacacg cttgataaga cttactccat ctaatacaac gagtgcaatt gtaccatctt taatagaatc 25761 ttctttctta ataaaagcgt atgttccttg ttttaacata ggttccattg aatcaccatt aactaaaata 25831 caaaaatcag catttgatgg cgtttcgtct tctttaaaaa atacttcttc atgcaatatg tcatcatata 25901 attcttctcc tatgccagca ccagttgcac cacatgcaat atacgatact agtttagact ctttatatc 25971 atctatagaa gtgactttat tctgttcttC caattgttca tttgcatagt taagtacgtt ttcttggcgg WO 00/32825 PCT/IB99/02040 180 26041 ggaggtgtga gtttgttgta tatggaagtg atgtcgttat cgtctttgta tgtagtattt gattcactat 26111 acaaatcatt aatcttcaca ttgaagtact cagccaaaat tttggcagtt gataatcgag gttcttcctt 26181 ttcattttcc cattttgata tcttgccttt cgttaatttc attaagtcgg gatatttatt attaagatca 26251 gttgctaatt gttccatagt catattttta tttttttctt agcttcttta aaccttcacc aatacccata 26321 cgaaaccctc cttatataag ataatttcat tataaaagtt tcgaaaacga aacgcaagga aaatattatt 26391 gcaaaagttg ttgaCatCga aacttttatg atgtattctt aaatcaagtt gttacaaacg aaacaaaagg 26461 agggggttca atgacaacta gtgtagcaga taaaccatac ttaaaaataa aaagcttgat tgcacttaaa 26531 ggaactaacc aaaaagaagt tgctaaagca atcggaatga gtagaagttt attgagtata aagataaatc 26601 gaattaatgg cagagatttt acaacttcag aagctaaaaa attagcagat catttaaatg ttaaagttga 26671 tgattttttt taaactttaa gtttcgaaag tgacaactaa ataaaaataa ggaggacact atggaacaaa 26741 taacgttaac caaagaagag ttgaaagaaa ttatagcgaa agaagttaga aatgctataa aaggcgagaa 26811 accaatcagc tcaggtgcaa ttttcagtaa agtaagaatc aataatgacg atttagaaga aatcaataaa 26881 aaactcaatt tcgcaaaaga tttgtcgcta ggaagattga ggaagctcaa tcatccgatt ccgctaaaaa 26951 agtatcagca tggcttcgaa tcaattcatc aaaaagctta tgtacaagat gttcatgacc atattagaaa 27021 attaacatta tcaatttttg gagtgacact taattcagac ttgagtgaaa gtgaatacaa cctagcagca 27091 aaaatttata gagatatcaa aaactattat ttatatatct atgaaaagag agtttcagaa ttaactatcg 27161 atgatttcga atgaaggagg aactacaaat gaaactacta agaaggctat tcaataaaaa acacgaaaac 27231 ttaattgacg tgtggcatgg aaatcaatgg ttaaaagtga aagaaagcaa attaaaaaaa tataaagtgg 27301 tctcggatag agaaggtaag aaatatctaa ttaaataagc gcacttaatt agtgcaagta atcaagtgcg 27371 ctattgcctt acaatcctaa atcttttctg cttttttctt cttcttgtaa tcccaataac acagaagagt 27441 aaatgctgaa atagtcacga gcaacgctat ctttagcgaa tgcaattacg tcatcaccga cttcttgcca 27511 ttcgttatga atcttatgtc tatctagagc tctaggtaat agcgagattg taatatcgtg agcaattttc 27581 tctaaatcca taaatttcaC ctccttccac tgggagataa ctaaattata taacaaaaca acttaaagga 27651 ggaacgacaa atgcaagctc aaaacaaaaa agtcatctat tactactatg acgaagaagg taataggcga 27721 ccattagata ttcaaattaa tgacggatat gaactgatgg tccgatctca tttcatcaac aacaccattg 27791 aagaaatacc atacgtaaat aataacttat atgccttggt tgatggitat gaatttaagt tagattgaat 27861 ttttgagaaa gatattgaaa agctaatttc cccataagat taagagacat actggatgtt ttgttaacga 27931 ctcttttaac ttcgttccaa gttttattgt ctctaatatt atcgagaaat tcatggccag accaagtgat 28001 gtcatcaata atccaagaaa cgaccctgcc ttcgatgaat ttcagatcgc aacaaataaa tttagcttct 28071 tctaatttta aaagtgagta cattactgtt tcaaaatcat atttatcaaa aataatatta tcgttgaaat 28141 tatgtcgagt aagtggttca cctattttct tattagattc tatttctaag agcaagagtc taacgcaatc 28211 gtgattaagt ttcatcctat cacctccata acaggagtat agcagaaagg atcataaaca tcttaaaagg 28281 aggaataaca aatgaacatt caagaagcaa ctaagatagc tacaaaaaat cttgtctcta tgacacggaa 28351 agattggaaa gaaagtcaic gaactaagat attaccaaca aatgatagtt ttttacaatg catcatttca 28421 aatagcgatg ggacaaacct tatcagatat tggcaacctt cagccgatga cctcatggca aatgattggg 28491 aagttataaa cccaactaga gaccaggaat tattgaagca attttagaaa tgctatcaat gatacttttt 28561 aaattgtttt taaactcatt ticaaagtaa acaacagtct tgtctgaaat tgttacatga taaatagtgt 28631 tactagcata cacgccgttt aggaacccag agtttttaag tttatttaaa tcgtatttta catcttcgaa 28701 atgtagtttt tgaaaatact ttgtatgtat atctttagca cttccaaaat tattgcaggt taatttaacc 28771 gaacctaact ttacacattc taaataatct ttgtagagta cggacaagat atattgttgg tctttagtaa 28841 gtgtatcaaa ttcatcagat atcaagggca tgttatcacc tccttaggtt gataacaaca ttatacacga 28911 aaggagcata aacaaatgaa cacaagatca gaaggattgc gtataggcgt cccacaagtt tctagcaaag 28981 ctgatgcttc ttcatcctat ttaacggaaa aggaacgtaa cttaggagcg gaaatattag agcttattaa 29051 aaaaagtgat tacagctact tagaaataaa caaagttttc tatgcattag atagagaact tcaatacagg 29121 gcgaataata acaaacttta acatttatct aaaggagtga tagagatgcc aaaaatcata ataccaccaa 29191 caccagaaaa cacatatcga ggcgaagaaa aatttgtgaa aaagttatac gcaacaccta cacaaatcca 29261 tcaattgttt ggagtatgta gaagtacagt atacaactgg ttgaaatatt accgtgaaga taatttaggt 29331 gtagaaaatt tatacattga ttattcagca acgggaacat tgattaatat ttctaaatta gaagagtatt 29401 tgatcagaaa gcataaaaaa tggtattagg aggattatca aatgagcgac acatataaaa gctacctatt 29471 agcagtgttg tgcttcacgg tcttagcgat tgtactcatg ccgtttctat acttcactac agcatggtca 29541 attgcgggat tcgcaagtat cgcaacattc atattttata aggaatactt ttatgaagaa taaagaaact 29611 gctacttgtt ggagcaagta acagtgcaag atgagcaatt gtcttaaata attatataag gagttattaa 29681 tatgacctta caacaaaaaa tactatcaca ttttgcaaca tatgacaatt tcaattctga tgatgttgtt 29751 gaagtttttg ggatatctaa aacacatgca aaatccacac tttcaagact taagaaaaaa ggaaagattg 29821 aattggaaag ttggggtatc tggcgtgttg ttgaaccgca gttacattta actgttgtag aacgtaagaa 29891 agagatatta gaagaacaat tcgagttatt ggcaagatta aacgaacaaa gtgatgaccc tagagaaata 29961 gaagaacgca tcaagttaat gattcgttta gccaaccaat tttaaggagg agttaatcaa tggcaatatt 30031 agaaggtatt tttgaagaat taaaactatt aaataagaat ttacgtgtgc taaatactga actatcaact 30101 gtagattcat caattgtaca agagaaagtt aaagaagcac caatgccaaa agatgaaaca gctcaactgg 30171 aatcagttga agaagttaag gaaacttctg ctgatttaac taaagattat gttttatcag taggaaaaga 30241 gttccttaaa aaagcagata cttctgataa gaaagaattt agaaataaac ttaacgaact tggtgcggat 30311 aagctatcta ctatcaaaga agagcattat gaaaaaattg ttgattttat gaatgcgaga ataaatgcat 30381 gaagctagat cactcaaata gagctcatgc aaagcttagt gcaagtggag caaaacaatg gctaaactgt 30451 ccaccgagta ttaaggcaag tgaaggtatt gcagataaaa gttcagtttt tgctgaagaa ggtacattcg 30521 ctcatgagtt aagtgagtta tatttcagtc ttaaatatga aggcctaaca cagtttgagt ttaataaagc 30591 ttttcaaaat tataagcgaa atcaatatta cagtgaagag ttgcgcgaat atgttgaaga gtacgtagct 30661 aatgtagaag aaaaatataa cgaagctttg agtagagatg acgatgtaat agctttattt gaaacaaaat 30731 tggatttagg taaatacgtc cctgaatctt ttggtactgg tgatgtcatt atattttcag gtggtgtact 30801 tgaaattatt gaccttaaat acggtaaagg cattgaagtt tcagctatag ataatcctca acttagatta 30871 tatggcttgg gcgcatatga actgcttagt ttaatgtatg acattcatac agttcgcaig actatcatac 30941 aaccacgaat agataacttt tctactgaag agttacCaat atcaagatta cttcaatggg gaaccgattt 31011 tgttaaacca ttagccagac ttgcttataa cggtgaaggt gagtttaaag caggtagtca ttgtagattc 31081 tgtaagataa agcattcatg tagaacacgt gcagaataca tgcaaaatgt gcctcaaaag ccaccacatt 31151 tgttgagtga tgaagagatt gcagaacttt tatataaact gcctgacatc aaaaaatggg ctgatgaagt 31221 agaaaaatat gcactagatc aagcgaaaga aaatgataaa aactattctg gttggaagct tgtagaaggt 31291 cgctcgcgaa gaatgataac tgatacaaat gcaacgcttg aaaagttagt tgaagcaggt tataaacctg WO 00/32825 PCT/IB99/02040 181 31361 aagatattac agaaaccaag ttacttagca ttacgaattt agaaaaatta atcggcaaaa aagcattttc 31431 taaaattgca gaaggcttta tagaaaagcc acaaggtaaa ttaacacttg ctaccgagtc tgataaacga 31501 ccagctataa agcaatctgc tgaagatgat tttgacaaac tataaaaatt aaaaaggacg gtatataaac 31571 atgaaagcaa aagtattaaa taaaactaaa gtgattacag gaaaagtaag agcatcatat gcacatattt 31641 ttgaacctca cagtatgcaa gaagggcaag aagcaaagta ttcaatcagt ttaatcattc ctaaatcaga 31711 tacaagtacg ataaaagcca ttgaacaagC tatagaagct gctaaagaag aaggaaaagt tagtaagttt 31781 ggaggcaaag ttcctgcaaa tctgaaactt ccattacgtg atggagatac tgaaagagaa gatgatgtga 31851 attatcaaga cgcttatttt attaacgcat caagcaaaca agcacctggt attattgacc aaaacaaaat 31921 tagattaacg gattctggaa ctattgtaag tggtgactat attagagctt caatcaattt atttccattc 31991 aacacaaatg gtaataaggg tatcgcagtt ggattgaaca acattcaact tgtagaaaaa ggcgaacctc 32061 ttggcggtgc aagtgcagca gaagatgatt tcgatgaatt agacactgat gatgaggatt tcttataagt 32131 caataggtgg ggtttttagc cccactttaa ttttaaagaa attgaggtgt caagaatttg aaatttatga 32201 atatagatat tgaaacatat agcagtaacg atatttcgaa atgtggtgtc tataaataca cagaagctga 32271 agatttcgaa atcttaatta tagcttattc aatagatggt ggaccgatta gtgcgattga catgactaaa 32341 gtagataatg agcctttcca cgctgattat gagacgttta aaattgctct atttgaccct gctgtaaaaa 32411 agtatgcatt caatgctaat ttcgaaagaa cttgtcttgc taaacatttt aataaacaga tgccacctga 32481 agaatggatt tgcacaatgg ttaattcaat gcgtattggc ttacctgctt cgcttgataa agttggagaa 32551 gttttaagac tacaaaacca aaaagataaa gcaggtaaaa atttaattcg ttatttctct ataccttgta 32621 agccaacaaa agttaatgga ggaagaacaa gaaatttgcc tgaacatgat cttgaaaaat ggcaacaatt 32691 tatagattac tgtattcgag atgtagaagt agaaatgaca attgCtaata aaattaaaga ctttccagta 32761 actgtaattg aacaagcata ttgggttttt gaccaaCata taaacgacag aggtattaag ctttctaaat 32831 cattgatgtt aggagctaat gtgctcgata agcagagtaa agaagaattg cttaaacaag ctaaacatat 32901 aacaggttta gaaaatccta atagtcctac acagttattg gcttggttaa aggatgaaca aggattagat 32971 atacctaatt tacaaaagaa aacggttcag gattacttaa aagtagcaac aggaaaagct aaaaaaatgc 33041 tagaaattag attgcaaatg tctaaaacca gtgtgaaaaa atacaacaaa atgcatgaca tgatgtgcag 33111 tgatgaacgg gtaagaggtc tgtttcaatt ctacggtgcc ggtactggaa gatgggcagg tagaggtgta 33181 caacttcaga atttaacaaa gcattatatt tcagatactg aattagaaat agcaagagat cttattaaag 33251 aacaacgttt tgacgattta gatttattac tcaatgttca tcctcaagac ttattaagtc aattagttag 33321 gacgacattt actgctgaag aaggtaatga actagcagta agtgattttt ctgcaataga ggcaagagtc 33391 atagcatggt atgcaaaaga acaatggcgt ttagatgtgt tcaacacaca cggaaagata tatgaagcat 33461 cggcttctca aatgtttaat gtaccggtag aaagcataac taaaggcgac cctctcagac aaaaaggaaa 33531 agtgtccgaa ttagctttag gctatcaagg tggcgctgga gctttaaaag caatgggtgc attggaaatg 33601 ggcattgaag aaaacgagtt acaaggttta gttgatagtt ggcgtaacgc aaatcctaac atagttaatt 33671 tttggaaggc ttgccaagag gctgcaatta atactgtaaa atcccgaaag acgcatcata cacatggact 33741 tagattttat atgaaaaaag gttttctaat gattgaactg cctagtggaa gagctttagc ttatccaaaa 33811 gctttagttg gtgaaaatag ttggggtagt caagttgttg aatttatggg gttagatctt aaccgtaaat 33881 ggtcaaagtt aaaaacgtat ggtgggaagt tagtcgagaa tattgttcaa gcaactgcaa gggatttact 33951 tgcgatttct atagcaaggc ttgaagcatt aggttttaaa atagttggcc atgtccatga tgaagtaatt 34021 gtagaaatac ctagaggttc aaatggactt aaggaaatcg aaactatcat gaataagcct gttgattggg 34091 caaaaggatt gaatttgaat agtgacgggt ttacttctCC gttttatatg aaggattagg agtgtgattg 34161 catgcaacat caagcttata tcaatgcttc tgttgacatt agaattccta cagaagtcga aagtgttaat 34231 tacaatcaga ttgataaaga aaaagaaaat ttggcggact atttatttaa taatccaggt gaactattaa 34301 aatataacgt tataaatatt aaggttttag atttagaggt ggaatgatgg ctagaagaaa agttataaga 34371 gtgcgtatca aaggaaaact aatgacattg agagaagttt cagaaaaata tcacatatct ccagaacttc 34441 ttagatatag atacaaacat aaaatgcgcg gcgatgaatt attgtgtgga agaaaagact caaaatctaa 34511 agatgaagtt gaatatatgc agagtcaaat aaaagatgaa gaaaaagaga gagaaaaaat cagaaaaaaa 34581 gcgattttga acctatacca acgaaatgtg agagcggaat atgaagaaga aagaaagaga agattgagac 34651 catggcttta tgatggaacg ccacaaaaac attcacgtga tccgtactgg ttcgatgtca cttataacca 34721 aatgttcaag aaatggagtg aagcataatg agcgtaatca gtaacagaaa agtagatatg aacgaagcgc 34791 aagacaatgt taagcaacca gcgcactaca catacggcga cattgaaatt atagatttta tcgaacaggt 34861 tacggcacag tatccacctc aactagcatt cgcaataggt aatgcaataa aatacttgtc tagagcacct 34931 ttaaagaatg gtcatgagga tttagcaaag gcgaagtttt acgtccaaag agcttttgac ttgtgggagt 35001 gatgaccatg acagatagcg catgtaaaga atacttaaac caatttttcg gatctaagag atatctgtat 35071 caggataacg aacgagtggc acatatccat gtagtgaatg gcacttatta ctttcacggg catatcgtac 35141 caggctggca aggcgtgaaa aagacatttg atacagcgga agagctcgaa acatatataa agcaacatgg 35211 tttggaatac gaggaacaga agcaactaac tttattttaa ggagatagaa atgatgaaaa tcaaagttga 35281 aaaaataatg aaaatagacg aattaattaa gtgggcgcga gaaaatccgg agctatcatt tggcagaaaa 35351 tattatacaa cagacaaaaa tgatgaaaac tttatttact tcggtgtttt taaaaattgt tttaaaataa 35421 gcgattttat attagttaat gctactttta gtgtcaaagt tgaagaagaa gtaaccgaag aaactaagtt 35491 tgataggttg tttgaagtgt acgagattCa agaaggagtc tataaatctg catcatatga gaatgctagt 35561 ataaacgaac gtttaaaaaa tgacagaatt tttcttgcta aagcattcta catcttaaac gacgacctaa 35631 ctatgacgtt aatttggaaa gaaggagagt tgattaaata atggaacacg gttcaaaaga atattacgaa 35701 aagcaaagtg aatactggtt tgatgaagca agcaagtttt tgaagcaacg tgatgagctt attggagata 35771 tagctaagtt aagagagtgc aacaaagagc tggagaagaa agcaagtgca tgggataggt attgcaagag 35841 cgttgaaaaa gatttaataa acgaatttgg caaagatggt gaaagagtta aatttggaat ggaattaaac 35911 aataaaattt ttatggagga agacgcaaat gaataaccgc gaacaaatcg aacaatcagt tattagtgct 35981 agcgcgtata acggcaatga cacagaggga ttattaaaag agattgagga cgtgtataag aaagcgcaag 36051 cgtttgatga aatacttgag ggtttaccta atgctatgca agatgcaatc aaagaagata ttggtcttga 36121 tgaagcagta ggaattatga cgggtcaagt tgtctataaa tatgaggagg agcaggaaaa tgactaacat 36191 attacaagtg aaactattat caaaagacgc tagaatgcca gaacgaaatc ataagacgga tgcaggttat 36261 gacatatttt cagctaaaac tgtcgtactt gagccacaag aaaaggcagt gatcaaaaca gatgtagctg 36331 taagcattcc agagggctat gtcggtttat taactagccg tagtggtgta agtagtaaaa cgcatttagt 36401 gattgaaaca ggcaagatag acgcgggata tcatggtaat ttagggatta atatcaagaa tgataatgaa 36471 acgttagaga gtgaggatat gagtaacttt ggtcggagtC cttctggtat agatggaaaa tacaccctaC 36541 tacctgtaac agataaattt ttatgtatga atggtagtta tgtcataaat aaaggcgaca aactagctca 36611 attggttatc gtgcctatat ggacacctga actaaagcaa gtggaggaat tcgagagtgt ttcagaacgt WO 00/32825 PCT/IB99/02040 182 36681 ggagcaaaag gcttcggaag tagcggagtg taaagacata ttagatcgag tcaaggaggt tttggggaag 36751 tgagtgacat gttagaaata tttttcatag ggtttggtgt ttatctattt tgtcgcatag gtattatttt 36821 tctcaagagt aaaaagacta tacacacaaa cctatatgaa atgttgttga ttgctactat ctttgtgaca 36891 tctacatttg ctgataaaca tcaaaagacg catatcttaa tagcattttt agtaatgttt tttatgagta 36961 agctcaaaca agttcaaggg agctatgagg aatgacacaa tacctagtca caacatttaa agattcaaca 37031 ggacgtaagc atacacacat aactaaagct aagagcaatc aaaggtttac agttgttgat gcggagagta 37101 aagaagaagc gaaagagaag tacgaggcac aagttaaaag aaatgcagtt attaaattag ggcagttgtt 37171 tgaaaatata agggagtgtg ggaaatgact aaacaaatac taagattatt attcttacta gcgatgtatg 37241 agctaggcaa gtatgtaact gagcaagtat atattatgat gacggctaat gatgatgcag aggcgccgag 37311 tgactttgaa aaaatcagag ctgaagtttc atggtaatag ctattatcat ttttgaatta attatattaa 37381 tgtgtttagc aatagcactg gaggtgttgt aaatatgtgg attgtcattt caattgtttt atctatattt 37451 ttattgatct tgttaagtag catttctcat aagatgaaaa ccatagaagc attggagtat atgaatgctt 37521 atcttttcaa gcagttagta aaaaataatg gtgttgaagg tatagaagat tatgaaaatg aagttgaacg 37591 aattagaaaa agatttaaaa gctaaagaga ggcgttggct tctctgttct atttaaaata atgaaaggag 37661 ccgaacatgt tagacaaagt cactcaaata gaaacaatta aatatgatcg tgatgtttca tattcttatg 37731 ctgctagtcg tttatctaca cattggacta atcacaatat ggcttggtct gactttatgc agaagctagc 37801 acaaacagtt agaactaaag aagatttaac tgagtacaat aaaatgtcta agtctgaaca agccgatata 37871 aaagatgttg gcggatttgt cggtggttat ttaaaagaag gcaaacgacg tgctggtcaa gtcatgaatc 37941 gttcaatgtt aacacttgat atcgattatg ctgctcaaga tatgactgac atattatcta tgttttatga 38011 ttttgcatat tgtttatatt caacacataa gcatagagag ataagtccaa gactgcgttt agtgattcct 38081 ttaaaacgaa atgtaaatgc agatgagtat gaagctattg ggcgtaaagt cgcagatatc gttggcatgg 38151 attacttcga tgatacaact tatcaaccac ataggttaat gtattggcct tcaactagta acgatgcgga 38221 atttttcttt acCtatgaag atttaccttt gttagaccca gataaaatat taaatgaata tgttgattgg 38291 actgacacat tagaatggcc aacgtcttca agggaagaga gtaagactaa aagattagca gataagcaag 38361 gcgacccaga agaaaagccg ggaattgttg qtgcattttg tagagcctat acgatagaag aagctataga 38431 aacttttatt cctgatttat acgaaaaaca ttctactaac cgttatacct atcatgaagg ttcaactgca 38501 ggtggattgg tgttatacga aaataacaag tttgcctatt ctcatcataa tacggatccc gtaagcggta 38571 tgcttgtgaa cagttttgat ttagtacgca tacacttata tggtgctcaa gatgaagacg ctaaaacaga 38641 tactccggtt aatcgactac ctagttataa agcaatgcag caaagagcgc aaaatgatga agttgttaaa 38711 aagcaattaa ttaacgacaa aatgtctgat gcaatgcagg atttcgatga aatagtaaat agcgatgatg 38781 catggtctga gacgttagaa attacttcga aaggtacttt caaagctagt atcccaaata tagaaattat 38851 attgcgtaat gatccaaatt taaaaggaaa aatagcattt aatgaattta caaaacaaat tgaatgctta 38921 gggaaaatgc catggaataa taattttaaa atacgtcaat ggcaagacgg tgatgatagc agtttaagaa 38991 gttatatcga aaagatttat gacatacacc attcaggcaa aacaaaagat gccattataa gcgtagcaat 39061 gcaaaatgcc tatcatccag taagagatta tctaaataaa atatcgtggg atggacataa acgtcttgaa 39131 aagttattta tcaaatactt aggtgttgaa gacactgaag tgaatagaac aactaccaaa aaggcattga 39201 ctgctggaat cgctcgagta atggagccag gatgtaaatt tgactatatg cttacacttt atggtcctca 39271 aggtgtaggt aaatctgctt tgctaaaaaa aataggtggt gcatggtttt ctgacagttt agttctgtt 39341 actggtaagg aagcatatga ggcattacaa ggcgtttggt taatggaaat ggcagaactt gcagctacaa 39411 gaaaagctga agttgaagct attaagcatt tcatatctaa acaagttgac cggtttcgtg ttgcttatgg 39481 acattatatt gaagattttc caaggcaatg tattttcatt ggtacaacta ataaagttga tttcttaaga 39551 gatgaaactg gtggaagacg tttttggcca atgactgtaa atccagagag agttgaagtg aactggtcta 39621 aactaaccaa agaagagatc gaccaaatct gggcagaagc taaatactat tatgaacaag gagaagagtt 39691 gttccttaac cctgaactag aagaagaaat gcgttcaatc caaagtaaac atactgagga atctccatat 39761 acaggtatta ttgatgaata tcttaacacg ccaatcccaa gcaattggga agacttaact atctttgaaa 39831 gaagacgatt ttatcaaggt gatgttgata tgttaccaac aggaaatgta gattacattg aaagagacaa 39901 ggtctgtgcg cttgaagtgt ttgttgaatg ttttggtaaa gataagggag atagtagagg atctatggaa 39971 attagaaaga tttctaacgt cttaagacaa ttagacaatt ggtctgtata tgaaggcaat aaaagtggga 40041 aaattcgatt tggaaaagat tatggtgtac agatagcgta tgtaagagat gaaagtttag aggatttaat 4 0111 ataagaaata ttgaataaat atacattttt agatgttgta tcaaatgttg catcattttt tgagtgatgc 40181 aacacggtgg tgtaaaaagt aatcgtaggt gttgtatcat ttttggtgat gcaacattga tgcaacaaat 40251 gatacaacac ctctttccct tctcgctgta aggttcaacc ctgtttgttt ccaatgttgc atcaaattca 40321 ctataaagtt taaaaagtag tgttagggag taaaggggta taggggtaac cctctaacag ctatttttaa 40391 aagtttggca agaattgatg caacatcgga acacaaatat aaattttgta tacaaggtga ataaatgaaa 40461 gaatcgacat tagaaaaata tttagtgaaa gagataacaa agttaaatgg attatgttta aaatgggtcg 40531 cacctggaac aagaggtgta ccagatagaa ttattattat gccagaagga aaaacatatt ttgtagaaat 40601 gaagcaagaa aagggaaagt tacatccttt acaaaaatat gtgcatcggc aatttgaaaa cagagatcat 40671 acagtgtatg tgttatggaa taaagaacaa gtaaatactt ttataagaat ggtaggtgga acatttggcg 40741 attgatttca aaccacatag ctatcaaaag tatgcaatag ataaagtgat tgataatgag aaatacggtt 40811 tgtttttaga tatggggcta gggaaaacag tatcaacact tacagcattt agtgaattgc agttgttaga 40881 cactaaaaaa atgttagtca tagcacctaa acaagttgct aaagatacat gggttgatga agttgataag 40951 tggaaccatt taaatcatct gaaagtgtct ttagtcttag gaacacctaa agaaagaaat gatgcattaa 41021 acacagaggc tgatatctat gtaaccaata aagaaaatac taaatggtta tgtgatcaat ataaaaaaga 41091 atggccattt gacatggttg taattgatga actgtctaca tttaaaagtc ctaagagtca aaggtttaaa 41161 tctattaaaa agaaattacc actcattaat agatttatag gattaacagg aacacctagt ccaaatagtt 41231 tacaggattt atgggctcaa gtttatttga tagacagagg cgaaagactt gagtcttcat tcagtcgtta 41301 tcgagaaagg tactttaaac caacacatca agttagcgaa catgttttta actgggagct aagagacgga 41371 tctgaagaaa agatatatga acgaatagaa gatatatgtt taagcatgaa agcgaaagat tatctggata 41441 tgcctgacag agttgatact aaacaaacag tagtcttatc tgaaaaagaa agaaaagtat atgaagaatt 41511 agaaaaaaac tatattttag aatcggaaga agaaggaaca gttgtagctc agaatggggc atcattaagt 41581 caaaaactac ttcaactatc taacggtgca gtttatacag atgatgaaga tgtaagactt atacagata 41651 agaagttaga taagttagag gaaattatag aggagtctca aggccaacca atattattgt tttataactt 41721 caaacatgat aaagaaagaa tacttcaaag gtttaaggaa gcaaccacat tagaggattc aaactataaa 41791 gaacgttgga atagtggaga cattaagctg cttatagcac atccagcaag tgcagggcat ggattaaact 41861 tacaacaagg tgggcacatt attgtttggt ttggacttac atggtcattg gaattatacc aacaagcaaa 41931 tgcaagatta tatagacaag gacaaaatca tacgactatt attcatcaca tcatgaccga taacacaata WO 00/32825 PCT/1B99/02040 1S3 42001 gatcaaagag tatataaagc tttacaaaat aaagaactaa cgcaagaaga attgatgaaa gctattaaag 42071 caagaatagc taagcataag taatggaggt ataagatggg aaaggcgtca tatgatatta agccaggaac 42141 atttaaatat attgaatcag aaatatataa tttaaatgag aacaagaaag agataaatag attgagaatg 42211 gagatactta acccaacgaa agaactagac accaacattg tgtatggacc gttacaaaaa ggagagccag 42281 ttagaacaac tgagttaatg gcgacaaggt tattgactaa taagatgtta cgtaacttag aagagatggt 42351 tgaagcagtt gaaagtgagt acttaaagtt acctgaagat cataagaaag taataaggtt aaagtattgg 42421 aataaagata agaagctaaa gatagaacaa ataggggatg cttgtcacat gcatcgcaat acagttacta 42491 caatacgaaa gaactttgtt aaagcgatag cgtatcatgc aggtatcaaa taacattgtg caaagattgt 42561 gcaaaaggcc tacaaatctg tagtaatatg atagtatCgg aaagatgtat aaagttatct gaaagttata 42631 cgacataaat acatgaggca catcgctaag CggtgtgtCt tttgttatgc aatcaaagag gtgtaagaga 42701 tgaccaagca taataacatt tataagcatg gtcgtaagtc atatcaatac gattggttct atcattcaaa 42771 agcatggaag aagttaagag agatagcatt agatagagat aattatcttt gtcaaatgtg tttacgcgaa 42841 gatattataa cagatgcaaa gattgtgcat cacattattt atgttgatga agattttaac aaagctttag 42911 acttagataa tctaatgtca gtttgttata gctgtcataa caaaattcat gcaaatgata atgacaaaag 42981 taatcttaag aaaattagag ttctaaaaat ttaaataaaa aaattattta aataaaattt tatgcccccc 43051 tgcccatcgg cttaaaatgt tttttcgccg ggtaccggag aggcc WO 00/32825 PCT/IB99/02040 184 Table 8 Bacteriophage 3A ORFs list SID LAN | FRA POS a.a. RBS sequence STA STO 100379 3AORF001 1 8515..13488 1657 acaggtacggatttaagaaaacttt ttg taa 100380 3AORFOO2 2 37667..40114 815 tttaaaataatgaaaggagccgaac atg taa 100381 3AORFOO3 1 32188..34149 653 ttaaagaaattgaggtgtcaagaat ttg tag 100382 3AORFOO4 3 17457..19370 637 gctattttattagaaaggaaggtgc att taa 100383 3AORFOO5 1 334..2034 566 agaaaaaagatagttcaagaagaag gtg taa 100384 3AORFOO6 1 15571..17154 527 cttttatttataggtaggtgattta atg taa 100385 3AORFOO7 2 19337..20836 499 atgatagtaaaacaagttcagggcc atg taa 100386 3AORFOO8 3 22176..23630 484 aatgatttagggtaggtgttgacca atg tga 100387 3AORFOO9 1 40726..42093 455 gtaaatacttttataagaatggtag gtg taa 100388 3AORFO1O 3 13491..14738 415 gaggcggactaacgctacagtaaaa att taa 100389 3AORF011 2 2039..3277 412 attaaagacataatgcgttaaggag gtg taa 100390 3AORF012 2 4001..5209 402 aaaaaagagaaaaaattaaacgcga atg taa 100391 3AORF013 1 30379..31545 388 attttatgaatgcgagaataaatgc atg taa 100392 3AORF014 2 14738..15562 274 attatatgggaggtttgactaatta atg tag 100393 3AORF015 3 3249..4034 261 cttgaattaagaaaatctttgaaag gtg tag 100394 3AORF016 -2 25587..26273 228 aagaagctaagaaaaaaataaaaat atg tga 100395 3AORF017 3 6729..7370 213 ttaatttttaaggaggaaataagca atg taa 100396 3AORF018 3 24540..25154 204 aataaaataaaaagtaggtgataag atg taa 100397 3AORF019 2 31565..32128 187 ctataaaaattaaaaaggacggtat ata taa 100398 3AORF020 3 36150..36713 187 gcagtaggaattatgacgggtcaag ttg taa 100399 3AORF021 2 24011..24535 174 gtaataaaatttataaagaaaggaa atg tga 100400 3AORF022 -2 - 12423..12938 171 taaagtaccagtagacaatgtaggt att tga 100401 3AORF023 1 7462..7917 151 aaaataaatcaaaggagaataattt atg taa 100402 3AORF024 1 26731..27174 147 actaaataaaaataaggaggacact atg tga 100403 3AORF025 1 42106..42543 145 taagcataagtaatggaggtataag atg taa 100404 3AORF026 2 35255..35671 138 aagcaactaactttattttaaggag ata taa 100405 3AORF027 2 5888..6298 136 atattggctataatacagtggtttt atc taa 100406 3AORF028 -3 27845..28255 136 ccttttaagatgtttatgatccttt ctg taa 100407 3AORF029 3 34344..34748 134 ttaaggttttagatttagaggtgga atg taa 100408 3AORF030 2 6299..6694 131 tataaaaaaggagttggccagataa atg tag 100409 3AORF031 1 20833..21225 130 ttaacaaaattataggagtgagaaa ata taa 100410 3AORF032 -2 39984..40361 125 aaatagctgttagagggttacccct ata tag 100411 3AORF033 1 7957..8325 122 gaatatctgcgtcttttttatttga ata taa 100412 3AORF034 -2 28506..28871 121 gttatcaacctaaggaggtgataac atg tag 100413 3AORF035 -2 10671..11036 121 tcctagcttcctaacagcaccgcca ata tga 100414 3AORF036 2 30020..30382 120 accaattttaaggaggagttaatca atg tga 100415 3AORF037 2 21818..22165 115 aagtgtaagtaatagttaagagtca gtg tag 100416 3AORF038 -2 42003..42347 114 gtactcactttcaactgcttcaacc atc tga 100417 3AORF039 2 21386..21727 113 tccagaaaatctagagtcataggtt ata taa 100418 3AORF040 -3 29654..29995 113 ttgattaactcctccttaaaattgg ttg taa 100419 3AORF041 -1 4333..4671 112 tactaaatctacatctgatccatga att tga 100420 3AORF042 3 5568..5900 110 taaaaaagtggtaggtgatttttaa atg tga 100421 3AORF043 1 25690..26019 109 taccaaattaatatagtcttcgcat ata tag 100422 3AORF044 3 29676..30005 109 gtcttaaataattatataaggagtt att taa 100423 3AORF045 3 30..353 107 cgctagcaacgcggataaatttttc atg taa 100424 3AORF046 3 | 27894..28214 106 aagatattgaaaagctaatttcccc ata tga 100425 3AORF047 -2 11907..12227 106 ttcgccgccaaaatgattagcattt ctg tga 100426 3AORF048 -3 40343..40663 106 ccataacacatacactgtatgatct ctg taa 100427 3AORF049 -3 6749..7069 106 tgttaaaccatcttcagattctcca ata taa 100428 3AORFOSO 1 42700..43014 104 ttatgcaatcaaagaggtgtaagag atg taa 100429 3AORF051 -2 13077..13388 103 ttgtacgtaatcccacacatcgccg att tga 100430 3AORF052 -3 3722..4024 100 gcatttcatttcctcctaataactc att tga 100431 3AORF053 3 17145..17444 99 tcgagacaatggatatagggagtgt att tag 100432 3AORF054 -1 19915. .20211 98 ataatttatagcttgcgaaacataa ata tga 100433 3AORFOSS -1 42436..42729 97 aatcgtattgatatgacttacgacc - atg -.-tag 100434 3AORF056 3 40455. .40745 96 taaattttgtatacaaggtgaataa a4g tga 100435 3AORF057 -1| 38665..38952 95 atcatcaccgtcttgccattgacgt att taa 100436 3AORF058 -1 -21265..21549 94 gaaatttctatctaacttgtcataa att tga 100437 3AORF059 -2 10278..10562 94 tttagccgcgcttccaactgcacgt att tag 100438 3AORF060 1 1 5278..5556 92 atatcagccgaataggggtgatgaa atg tag 100439 3AORF061 1 35668..35946 92 tttggaaagaaggagagttgattaa ata taa 100440 3AORF062 2 35912..36187 91 gttaaatttggaatggaattaaaca ata taa WO 00/32825 PCT/IB99/02040 185 100441 3AORF063 3 36720..36995 91 cggaagtagcggagtgtaaagacat att tga 100442 3AORF064 -2 35694..35969 91 ccgttatacgcgctagcactaataa ctg taa 100443 3AORF665 -2 32697. .32972 91 aaccgttttcttttgtaaattaggt ata taa 100444 3A0RF066 3 29157. .29429 90 caaactttaacatttatctaaagga gtg tag 100445 3AORF067 -2 26661..26930 89 atacttttttagcggaatcggatga ttg taa 100446 3AORF068 -2 9624..9893 89 ttttaatgcatctcccatgtattga ata tga 100447 3A0RF069 -3 13847. .14110 87 tgcatttcctcctgattcgtgttga atc Itga 100448 3AORF070 1 34993. .35250 85 tttacgtccaaagagcttttgactt gtg taa 100449 3AORF071 2 34745. .35002 85 aaatgttcaagaaatggagtgaagc ata tga 100450 3A0RF072 -1 27379..27636 85 tttgtcgttcctcctttaagttgtt ttg taa 100451 3A0RF073 2 37367..37615 82 tggtaatagctattatcatttttga att taa 100452 3A0RF074 -2 23466. .23714 82 cgtttgtttttttaaaatttaatat att taa 100453 3A0RF075 -3 2471. .2719 82 agtactgtttgaaatcttctaacac ttg tga 100454 3A0RF076 1 26047. .26292 81 aagtacgttttcttggcggggaggt gtg tag 100455 3AORF077 2 28292..28537 81 aacatcttaaaaggaggaataacaa atg tag 100456 3AORF078 -1 5836..6075 79 ttttgtataaggcttagatttagtc att taa 100457 3AORF079 -2 5460..5699 79 attcagtcgcttttaaaatttctct atc taa 100458 3AORFO8O -2 31350. .31586 78 cctgtaatcactttagttttattta ata taa 100459 3AORF081 -3 8252..8488 78 aagttttcttaaatccgtacctgta atg tga 100460 3AORF082 -1 35905..36138 77 atatttatagacaacttgacccgtc ata taa 100461 3AORF083 -1 34039. .34272 77 atagttcacctggattattaaataa ata tga 100462 3A0RF084 -1 12007. .12240 77 acatttttttcatttcgccgccaaa atg taa 100463 3AORF085 -2 32367..32591 76 cttacaaggtatagagaaataacga att taa 100464 3A0RF086 -2 30618..30848 76 atataatctaagttgaggattatct ata taa 100465 3AORF087 -3 24746..24973 75 ataggttttaagttcaccctcttca atg tga 100466 3AORF088 -3 12980..13204 74 tctttctttttcgtaccaccatgga att tag 100467 3A0RF089 3 4290. .4508 72 acaggagaagcttatcaatctttaa atg taa 100468 3AORF090 3 28926..29141 71 ttatacacgaaaggagcataaacaa atg taa 100469 3AORF091 -2 13587. .13802 71 cttgtcttgctaattgcttagataa atg tag 100470 3A0RF092 2 26471..26683 70 aaacgaaacaaaaggagggggttca atg taa 100471 3AORF093 -1 2524..2736 70 tccaccgttttcttcatagtactgt ttg tga 100472 3AORF094 -3 25334..25546 70 tggcgctttaatataaaagacgtct att tga 100473 3AORF095 3 8316. .8525 69 1aagagatgggaaagacagaagaaca atc tag 100474 3A0RF096 2 36992. .37198 68 aacaagttcaagggagctatgagga atg tga 100475 3A0RF097 -1 32593. .32799 68 aaagcttaatacctctgtcgtttat atg taa 100476 3A0RF098 -1 15346. .15552 68 aatccattaaatcacctacctataa ata tag 100477 3A0RF099 1 7225. .7428 67 actggtgactggatgaacagaaaag ttg tag 100478 3AORF100 -2 22620. .22823 67 cgacttcatgaccggcatgtcttaa ata taa 100479 3AORF101 -1 40060. .40260 66 aaccttacagcgagaagggaaagag gtg taa 100480 3AORF102 -1 35035. .35235 66 ttctatctccttaaaataaagttag ttg taa 100481 3AORF103 -2 1149. .1349 66 atttttttggagtgttgggtaatca ata taa 100482 3AORF104 1 27661. .27858 65 aaacaacttaaaggaggaacgacaa atg tga 100483 3AORF105 -2 9420. .9617 65 gcctaagtcaaccgcttgattagac atg tga 100484 3AORF106 -2 23244. .23438 64 caccagtaattcttgaattagttga ata taa 100485 3AORF107 2 11966. .12157 63 tctaaaaaagatgctgtagtagacg ttg taa 100486 3AORF108 -3 35054.a.35245 63 ttttcatcatttctatctccttaaa ata tag 100487 3AORF109 -3 16010.16201 63 1gttcttaattccaatgtactgacag ttg taa 100488 3AORF110 -1 6184. .6372 62 attttcagtgactttataatagtat att taa 100489 3AORF111 -2 16500. .16688 62 gtagtcaacaattgctttgtattga ttg tga 100490 3AORF112 -2 8502.a.8690 62 cttaattctcgcctgatacttttcc att taa 100491 3A0RF113 1 34162.c.34347 61 tatgaaggattaggagtgtgattgc atg tga 100492 3AORF114 2 12356. .12541 61 ggatatcacactaaggctatagcta ata taa 100493 3AORF11S -2 7635.a.7820 61 tgaagttccctcagctacaccgtga att tga 100494 3AORF116 -1 26434. .26613 59 tttagcttctgaagttgtaaaatct ctg tga 100495 3AORF117 -3 17804. .17983 59 atagccattatttctagcttgtgtc atg tga 100496 3AORF118 2 27899. .28075 58 attgaaaagctaatttccccataag att taa 100497 3AORF119 -1 39268. .39444 58 acgaaaccggtcaacttgtttagat atg tga 100498 3AORF120 -2 37152.c.37328 58 tagctattaccatgaaacttcagct ctg taa 100499 3AORF121 -2 18900. .19076 58 aaggtactctctcccatttaccact att taa 100500 3A0RF122 -1 21550. .21723 57 1taagcatggtaatcacctcctttaa atg taa 100501 3A0RF123 -3 33062. .33235 57 aaacgttgttctttaataagatctc ttg tag 100502 3A0RF124 2 21212. .21382 56 aaattagaagaggttaaaggagaga ctg tag 100503 3AORF125 -1 22051..22221 56 aaatcaggattgaactgcttcccta atg tga 100504 3AORF126 -2 7821..7991 56 tgtttttcctgttttacggtcttta att tga 100505 3A0RF127 -3 34712..34882 56 ttgcattacctattgcgaatgctag ttg taa 100506 3A0RF12B -3_ 24056. .24226 56 tttttaaaatcaaagcgtctttgtt -ata -- taa 100507 3A0RF129 -3 4940..5110 56 cataccatgcagttaatacaaacaa ata tga 100508 3AORF130 3 27171. .27338 55 cagaattaactatcgatgatttcga atg taa 100509 3AORF131 -1 40387..40554 55 1ccttctggcataataataattctat ctg taa 100510 3A0RF132 -2 1860. .2027 55 gcgataacattcacctccttaacgc att tga 100511 3A0RF133 -3_ 42317. .42484 55 acaaagttctttcgtattgtagtaa ctg tag 100512 3A0RF134 2 12671. .12835 54 tcatacaaatctttaaaaggttgga ctg tag WO 00/32825 PCT/IB99/02040 186 100513 3AORF135 -1 39484..39648 54 ataatagtatttagcttctgcccag att taa 100514 3AORF136 1 29710..29871 53 accttacaacaaaaaatactatcac att taa 100515 3A0RF137 1 37186..37347 53 ggcagttgtttgaaaatataaggga gtg taa 100516 3A0RF138 2 20996..21157 53 aatggggaaatagtttttaacgaag att taa 100517 3A0RF139 3 15114..15275 53 tcaactgaaattgaagtaagtttaa atg taa 100518 3A0RF140 3 29442..29603 53 aaaatggtattaggaggattatcaa atg taa 100519 3AORF141 -1 39883..40044 53 tacaccataatcttttccaaatcga att taa 100520 3A0RF142 -1 20416..20577 53 accacctggaaaagtcccataaaaa att tga 100521 3A0RF143 -1 1942..2103 53 ataaagcttagaagttgactgatca atc taa 100522 j3A0RF144 -3 39380. .39541 53 ttccaccagtttcatctcttaagaa atc taa 100523 j3ARF145 3 20388..20546 52 tctgagtggtcagaattagctatta atg taa 100524 3A0RF146 -2 2358..2516 52 aacatgtccatattatgaacaatca att tga 100525 3AORF147 -3 5606..5764 52 gtgatttgtttgtggtagatattca att tga 100526 3A0RF148 2 34145..34300 51 tttacttctccgttttatatgaagg att taa 100527 3AORF149 -1 7918..8073 51 tattctcttgatttactaattctaa ata taa 100528 3AORF150 -2 11745..11900 51 ttcatccttatgtctttgatcagca ata taa 100529 3AORF151 -3 7097..7252 51 tttaccttcatgatacccgtataca ata tga 100530 3AORF152 1 21652..21804 50 ctaaaaatattagagacatcaagat gtg taa 100531 3A0RF153 2 5381..5533 50 tcggctaagtctgaattactattaa gtg tga 100532 3AORF154 -1 39670..39822 50 ttgataaaatcgtcttctttcaaag ata taa 100533 3AORF155 -1 38233. .38385 50 ataggctctacaaaatgcaccaaca att tag 100534 3A0RF156 -1 33040.33192 50 tatctgaaatataatgctttgttaa att tag 100535 3A0RF157 -2 10119. .10271 50 cttcaatgatttgctatagctatta att tga 100536 3AORF158 -3 36074..36226 50 atccgtcttatgatttcgttctggc att taa 100537 3AORF159 -3 18338..18490 50 taaatagtttctattatttggatta ctg taa 100538 3AORF160 3 39399. .39548 49 gtttggttaatggaaatggcagaac ttg Itaa 100539 3AORF161 -2 8976..9125 49 ttgtacttttagtttttgaacttga ttg tga 100540 3AORF162 -3 31199..31348 49 tctgtaatatcttcaggtttataac ctg tga 100541 3AORF163 -3 14459..14608 49 attatcctgagaagaaacagtttga atc tga 100542 3A0RF164 3 25182..25328 48 ttttttcttagctttttctgataaa gtg tag 100543 3AORF165 3 28353..28499 48 aatcttgtctctatgacacggaaag att taa 100544 3A0RF166 -1 8899..9045 48 gtactgcgtcacttgctctttttag ttg taa 100545 3AORF167 -2 411..557 48 taatacaagttgacgtttagatcct ttg tga 100546 3AORF168 -3 25973..26119 48 gctgagtacttcaatgtgaagatta atg tag 100547 3AORF169 -3 25151..25297 48 aaaaaaacgcctacaagtgtagacg ttg tag 100548 3AORF170 -3_ 24995. .25141 48 taagaaaaaagattagtattcattc att tag 100549 3AORF171 1 23437..23580 47 aaaggtaataacgtaagggacggct att tag 100550 3AORF172 2 32414..32557 47 ctatttgaccctgctgtaaaaaagt atg taa 100551 3A0RF173 -1 38005. .38148 47 ataagttgtatcatcgaagtaatcc atg taa 100552 3A0RF174 -1 4123..4266 47 atttaaagattgataagcttctcct gtg tga 100553 3AORF175 -1 3124..3267 47 ttcatttgaaaatacttagctttca ttg tag 100554 3AORF176 -1 580..723 47 cattttctccatcttgtgatacagc ata taa 100555 3A0RF177 -2 39819..39962 47 ttagaaatctttctaatttccatag atc tag 100556 3A0RF178 -2 38466..38609 47 ttagcgtcttcatcttgagcaccat ata tag 100557 3AORF179 -2 33927..34070 47 ttttgcccaatcaacaggcttattc atg tga 100558 3AORF180 -2 33555..33698 47 cgtctttcgggattttacagtatta att tga 100559 3AORF181 -2 29538..29681 47 atagtattttttgttgtaaggtcat att tga 100560 3A0RF182 -3 17099..17242 47 aatatcactactgcctgcataaggt atc tag 100561 3A0RF183 2 23750..23890 46 ttaaaaaaacaaacgtttttagtat ata taa 100562 3AORF184 -1 31648..31788 46 tggaagtttcagatttgcaggaact ttg tga 100563 3AORF185 -1 30565..30705 46 attttgtttcaaataaagctattac atc tag 100564 3A0RF186 -1 16951..17091 46 gagaattcaaagtactagtgtataa atg tga 100565 3A0RF187 -1 7153. .7293 46 tatccaacgaatacttttttgaaga att taa 100566 3ARF188 -1 1237. .1377 46 ccagctcttctaaagaaacaatttc att taa 100567 3A0RF189 -2 133309..33449 46 catttgagaagccgatgcttcatat atc tga 100568 3AORF190 -2 7197..7337 46 gtaacgaacttgcagaatcCtctga atg taa 100569 3AORF191 -3 41459..41599 46 tcatctgtataaactgcaccgttag ata tag 100570 3A0RF192 3 4863..5000 45 gatgctattattaacgctttagcag att tag 100571 3A0RF193 3 25965. .26102 45 tatacgatactagtttagactcttt ata tga 100572 3A0RF194 -1 37069..37206 45 ctagtaagaataataatcttagtat ttg tga 100573 3AORF194 -1 11749. .11886 45 tttgatcagcaatagctaataattt atc tga 100574 3A0RF196 -2 40764..40901 45 atctttagcaacttgtttaggtgct atg tga 100575 3A0RF197 -2 31989. .32126 45 ggctaaaaaccccacctattgactt ata tga 100576 3A0RF198 -3 36431. .36568 45 tttatttatgacataactaccattc ata tga 100577 3A0RF199 -3 33515. .33652 45 ttccaaaaattaactatgttaggat ttg tga 100578 3AORF200 -3 21233..21370 45 ataagattataacctatgactctag attL -tga 100579 3AORF2011 1 23293. .23427 44 aagcctatcggtggtgtgatatcta ata taa 100580 3AORF202 -1 39088..39222 44 atagtcaaatttacatcctgctcc att taa 100581 3ARF203 -1 16309..16443 44 tttgcttgccgtctaaaatcaactt ata tga 100582 3A0RF204 1 23845. .23976 43 atgtttattatcaatcaaaatataa att taa 3AORF20 1 29500..29631 43 gtgttgtgcttcacggtcttagcga ttg t 3ARF206 2 16667..16798 43 gaaaaatcaacagtcttaaatttaa ttg tg WO 00/32825 PCT/IB99/02040 187 100585 3A0RF207 1-1 35386..35517 43 tgcagatttatagactccttcttga atc taa 100586 3A0RF208 1 -1 30013..30144 43 cagttgagctgtttcatcttttggc att taa 100587 3A0RF209 -1 28366. .28497 43 taattcctggtctctagttgggttt ata tga 100588 3AORF210 -1 15739..15870 43 catcaagcttatttgattccactga gtg tag 100589 3AORF211 -1 7693..7824 43 taactgaagttCcctcagctacacc gtg tga 100590 3AORF212 -2 4314..4445 43 ggttctgaaacaatttctttagaaa gtg tag 100591 3AORF213 -2 4011. .4142 43 tgtttgatgtcttccatatcaatat ttg taa 100592 3AORF214 -2 1722..1853 43 tctgtctagtttcaactgaacatta ttg taa 100593 3AORF215 -3 16616..16747 43 tcttcatttgtttgcgtattagcat atc tag 100594 3A0RF216 -3 15833..15964 43 gtcattttgaccgaagttttttgat ttg taa 100595 3A0RF217 3 6363..6491 42 gatgcagagctccaaacatatataa att taa 100596 3AORF218 -1 32146..32274 42 aataagctataattaagatttcgaa atc taa 100597 3A0RF219 -1 29800..29928 42 ctagggtcatcactttgttcgttta atc taa 100598 3AORF220 -1 18409. .18537 42 gcattaacctgatacgcttcttctc ctg tag 100599 3A0RF221 -1 13234..13362 42 ttttatcgcctaaccaagatgcacc atc tag 100600 3A0RF222 -1 12313..12441 42 cccaagctttatctgaggcatctga ata tga 100601 3A0RF223 -1 4915. .5043 42 tccatcatagttaattccaaaataa ttg taa 100602 3A0RF224 -1 2125. .2253 42 attaactactttataatcttcatac att taa 100603 3A0RF225 -2 26298..26426 42 tcgtttgtaacaacttgatttaaga ata taa 100604 3A0RF226 -2 17184..17312 42 cgcctatttttaaattatctaattt att tag 100605 13ARF227 -2 1425. .1553 42 atcttcttcccattctctatagggt att taa 100606 3ARF228 -3 31055..31183 42 cattttttgatgtcaggcagtttat ata taa 100607 3A0RF229 -3 22592. .22720 42 gttataaccatgaccggctacaagc ata taa 100608 3AORF230 -1 27883..28008 41 gaaggcagggtcgtttcttggatta ttg tag 100609 3A0RF231 -2 29988..30113 41 gcttctttaactttctcttgtacaa ttg taa 100610 3A0RF232 -2 22485. .22610 41 tatctgggaaatttaatctaataaa ata tag 1 100611 3A0RF233 -2 9264. .9389 41 aagtttgccgaaatgactttgagct atc tga 100612 3A0RF234 -3 23033. .23158 41 acctaattcagataagcgataattt ata tga 100613 3A0RF235 1 25558. .25680 40 aacactgctgaaatagacgtctttt ata tag 100614 3A0RF236 1 34420. .34542 40 acattgagagaagtttcagaaaaat atc taa 100615 3A0RF237 3 38442. .38564 40 gaagaagctatagaaacttttattc ctg taa 100616 3A0RF238 -1 33628. .33750 40 caatCattagaaaaccttttttcat ata taa 100617 3A0RF239 -1 29248. .29370 40 tcttctaatttagaaatattaatca atg tag 100618 3A0RF240 -2_ 18156. .18278 40 gtCtctcaattctgtatagaatttt att taa 100619 3A0RF241 -2 8088. .8210 40 tttcaaggcttttgtataagtttta gtg tga 100620 3A0RF242 -3 39149. .39271 40 ttagcaaagcagatttacctacacc ttg taa 100621 3A0RF243 -3 23558. .23680 40 aaaattaactgtttattaattttaa ata taa 100622 3A0RF244 -3 1697. .1819 40 catttcattaaaggattattattaa ata tga 100623 3A0RF245 1 19015. .19134 39 attatgcaaggaatatgatgactt ttg tag 100624 3A0RF246 1 22504. .22623 39 gctaatctaaacactttcacatcgt ttg taa 100625 3A0RF247 -1 40567. .40686 39 aaagtatttacttgttctttattcc ata taa 100626 13A0RF248 -1 23956. .24075 39 tttagattcatgaaacgaagtagca ata taa 100627 3A0RF249 -1 11113. .11232 39 cacctttccccaacacttttacagt atc tga 100628 3AORF250 -1 8719.-8838 39 ttttattagcttctactagctttaa ata taa 100629 3AORF251 -2 16899. .17018 39 aactcgtctgttaagcgcttgttga att tga 100630 3A0RF252 -3 37025. .37144 39 acaactgccctaatttaataactgc att tga 100631 3A0RF253 -3_ 29138. .29257 39 tctacatactccaaacaattgatgg att taa 100632 3A0RF254 -3 15476. .15595 39 caaatcaattcattaaaatccatta ctg taa 100633 13A0RF255 1 13552. .13668 38 ttaatagacaaagtaaaatcgtggt ttg tag 100634 3A0RF256 2 12545. .12661 38 aaaagtgcaaagggctggctaacgg ata taa 100635 3A0RF257 2 41870. .41986 38 gggcatggattaaacttacaacaag gtg tga 100636 3A0RF258 3 10827. .10943 38 tcaaacttttgaaaaacggtttagg att taa 100637 3A0RF259 -1 34570. .34686 38 gtgacatcgaaccagtacggatcac gtg tga 100638 3A0RF260 -1 32389. .32505 38 aagcaggtaagccaatacgcattga att tag 100639 3AORF261 -1 23830. .23946 38 cctttttaacttttaataaaattaa ata tga 100640 3A0RF262 -1 8158. .8274 38 ccatctcttctggttcagtttctga atc taa 100641 3A0RF263 -2 14001. .14117 38 ttatacctgcatttcctcctgattc gtg tga 100642 3A0RF264 -2 294. .410 38 -tttgCttgtttttattttCccttga gtg taa 100643 3A0RF265 -3 42683. .42799 38 tgacaaagataattatctctatcta atg tga 100644 3A0RF266 -3 31979. .32095 38 aatcctcatcatcagtgtctaattc atc taa 100645 3A0RF267 -3 26306. .26422 38 ttgtaacaacttgatttaagaatac atc tga 100646 13A0RF268 -3 16490. .16606 38 tacatacaaggcttagcttttttat ttg tag 100647 3A0RF269 -3 9872. .9988 38 tgagacccctctaaccctgagttag ata tag 100648 3A0RF270 1 21829. .21942 37 atagttaagagtCagtgcttcggca ctg tag 100649 3A0RF271 2 29468. .29581 37 tgagcgacacatataaaagctacct att-- taa. 100650 3A0RF272 3 2955. .3068 37 gagttaaacagattttacttgcagc ata-L a 100651 3AORF273 3 5010. .5123 37 tttggcaaaccagtagtatttacag atg taa 100652 3A0RF274 3 19956. .20069 37 tcaagtatagatgaattaaagcaac ttg tga 100653 13A0RF275 3 39882. .39995 37 gatatgttaccaacaggaaatgtag att taa 100654 3A0RF276 -1 27211. .27324 37 attaagtgrcgcttatttaattagat att tga 100655 3A0RF277 -1 13516. .13629 37 cgaccgtcattaaagttaagtccac ctg tga 100656 3A0RF278 -1 11893. .12006 37 ttttatatacacgaccactggataa atc taa WO 00/32825 PCT/IB99/02040 188 100657 3AORF279 -2 17535..17648 37 tttgtaaagatttgtttactgctgc ttg taa 100658 3AORF280 -2 6474..6587 37 tcaaaataagcatctaactgactag atg taa 100659 3AORF281 -2 759..872 37 ttttgatatcgttgcgtcataatgg att tga 100660 3AORF282 -3 36608..36721 37 cccaaaacctccttgactcgatcta ata tga 100661 3AORF283 -3 14960..15073 37 tttcagttgaagaaccatcttttaa att taa 100662 3AORF284 1 18859..18969 36 atgttaacagagccaggtctttact att taa 100663 3AORF285 2 8237..8347 36 aaaacttatacaaaagccttgaaag ata taa 100664 3AORF286 3 5157..5267 36 tatgatcagcaacgtacattagaca gtg tag 100665 3AORF287 3 38610..38720 36 tttgatttagtacgcatacacttat atg taa 100666 3AORF288 -1 36454..36564 36 tttatgacataactaccattcatac ata tga 100667 3AORF289 -1 30217..30327 36 aacaattttttcataatgctcttct ttg taa 100668 3AORF290 -1 16678..16788 36 gcttttttgcaaattctaacagctt atc tga 100669 3AORF291 -2 14310..14420 36 gtctagttaaagggataaccatctc ctg tga 100670 3AORF292 -2 11457..11567 36 ttctttcaattctttgattttctga ttg tga 100671 3A0RF293 -3 29462..29572 36 ttcataaaagtattccttataaaat atg tag 100672 3AORF294 -3 22388..22498 36 accattccaattttggccaaacgat gtg tag 100673 3A0RF295 -3 18629..18739 36 aaaaggaacgcctcttgagtgaagt att tag 100674 3AORF296 -3 6332..6442 36 tatcagacatgaagtctgaaggtaa atc taa 100675 3AORF297 1 13984..14091 35 aaatggttgaagtcacttaaaggta gtg tag 100676 3AORF298 1 40174..40281 35 tatcaaatgttgcatcattttttga gtg taa 100677 3A0RF299 2 1481. .1588 35 gccgcgtgtgctacttttgcgttag ata taa 100678 3AORF300 2 40451..40558 35 aatataaattttgtatacaaggtga ata tag 100679 3AORF301 3 25479..25586 35 accactagttaaaacttcatatact ata taa 100680 3AORF302 3 32106..32213 35 gaagatgatttcgatgaattagaca ctg tga 100681 3A1RF303 3 36024..36131 35 gacacagagggattattaaaagaga ttg tag 100682 3A2RF304 -1 37762..37869 35 accgacaaatccgccaacatctttt ata tga 100683 3AORF30 -1_ 24088..24195 35 tttatctttaacaaaatcaaactga ata tga 100684 3ARF306 -1 19507. .19614 35 atcattaggtaattgaaattttaaa ata tga 100685 3A0RF307 -1 16081..16188 35 atgtactgacagttgcagatacagt aic tag 100686 3A0RF308 -1 11398..11505 35 tttctttagttctagttaaaatgtt ttg taa 100687 3ARF309 -2 33003.t.33110 35 aaacagacctcttacccgttcatca ctg taa 100688 3AORF310 -2 24894..25001 35 gtaaatcgaaatcgctaccagctga att taa 100689 3A0RF311 -2 22005..22112 35 ttcgtaggtgtcattacttctttaa ttg tag 100690 3A3RF312 -2 21711..21818 aaaataaaaagccagtgccgaagca ctg tag 100691 3AORF313 -2 17901..18008 35 cattaggtcttagacgacttagcat ata taa 100692 3AORF314 -2 16710..16817 35 taattcagtcttaggagtatcattt att tag 100693 3A0RF315 -2 15990..16097 35 acatatctccgtatcatttgggtaa att tag 100694 3AORF316 -2 2862..2969 35 aattcttcttcatactgtttgacga ttg tag 100695 3AORF317 -3 40217..40324 35 tccctaacactactttttaaacttt ata tga 100696 3AORF318 -3 37535..37642 35 tgttcggctcctttcattattttaa ata taa 100697 3A0RF319 -3 34421..34528 35 ttcttcatcttttatttgactctgc ata tga 100698 3AORF320 -3 28262. .28369 35 catttgttggtaatatcttagttcg atg tga 100699 3AORF321 1 23989..24093 34 taaaaaggtttaatataaaaatgta ata tga 100700 3AORF322 1 34660..34764 34 aagagaagattgagaccatggcttt atg taa 100701 3AORF323 3 30105..30209 34 ctaaatactgaactatcaactgtag att taa 100702 3AORF324 3 30258. .30362 34 ggaaaagagttccttaaaaaagcag ata tga 100703 3AORF325 3 40236..40340 34 gttgtatcatttttggtgatgcaac att tag 100704 3A0RF326 -1- 36964. .37068 34 cgcatcaacaactgtaaacctttga ttg tga 100705 3A0RF327 -1 35242..35346 34 atttttgtctgttgtataatatttt ctg taa 100706 3A0RF328 -1 21916..22020 34 ccatttaccttcttgagatgttgga ttg tga 100707 3A0RF329 -1 18820. .18924 34 ggtggcttaacttccaagaaccaac ctg taa 100708 3A0RF330 -1 15631..15735 34 ttatgaagttttcacaaattagtaa atc tag 100709 3A0RF331 -2 37998. .38102 34 ttacgcccaatagcttcatactcat ctg tag 100710 3AORF332 -2 7359..7463 34 tttataaacctttaaagttttagtc ata taa 100711 3A0RF333 -3 24584. .24688 34 aaaaattataaaactataaaaccat atc taa 100712 3AORF334 -3 24269..24373 34 tatttttaggtagataatttattaa atc tga 100713 3A0RF335 -3 14273. .14377 34 cacttcagcaagttgatgctttgta atc tga 100714 3A-RF336 2 7559..7660 33 gtaactttatctaatttagaagcgg ata tag 100715 3A0RF337 2 13277. .13378 33 aatataggtaaaaaagcaggagaat ttg tag 100716 3AORF338 3 9501..9602 33 taggacgtacgatgacgatgggcgt atc taa 100717 3AORF339 3 27348..27449 33 atatctaattaaataagcgcactta att tga 100718 3A0RF340 -1 37372..37473 33 ttctatggttttcatcttatgagaa atg taa 100719 3A0RF341 -1 33421. .33522 33 aagctaattcggacacttttccttt ttg taa 100720 3A0RF342 -1 29047.a.29148 33 tttggcatctctatcactcctttag ata taa 100721 3A0RF343 -1 7549. .7650 33 atgatacgcctgagactagaattgg att- taa 100722 3A0RF344 -1 7297.. 7398 33 ctgctgaaactgttgcagattttga att- 1 - -tga 100723 3A0RF345 -2 23850. .23951 33 ttaaacctttttaacttttaataaa att taa 100724 3A0RF346 -2 20607. .20708 133 aaagatgtacgactagatttagtta atc taa 100725 3A0RF347 -2 14175. .14276 33 1atctgttgttaaagaacgctaataa ctg taa 100726 3A0RF348 -2 6984. .7085 33 cgtacactggttgacctgttaaacc atc tag 100727 3A0RF349 -2 6882. .6983 33 tagaacgaccaataactgtatttag att taa 100728 3A0RF350 -3 40748..40849 33 aactgcaattcactaaatgctgtaa gtg tga WO 00/32825 PCT/IB99/02040 189 100729 3A0RF351 -3 38345..38446 33 ggttagtagaatgtttttcgtataa atc taa 100730 3AORF352 -- 3 38081..38182 33 tagttgaaggccaatacattaacct atg taa 100731 3AORF353 -3 35432..35533 33 tagcattctcatatgatgcagattt ata taa 100732 3A0RF354 -3 34952..35053 33 ttatcctgatacagatatctcttag atc taa WO 00/32825 PCT/IB99/02040 190 Table 9 Bacteriophage 96, complete genome sequence 1 catagttata ggcttttcag ctatatacca agataagatt tatcccgccg tctccataaa aatatgcttg 71 gaaaccttga tttaatgggg ttttaatcta gcaagtgtca aatatgtgtc aagaaaataa ttttctgaca 141 cgttgacctt gctctttttt atgttcatca agtaagtgag agtaggtgtc taaagttata gatatattat 211 aatggcctaa tcttttgcta atatattcaa taggtatacc tttagaaagt aggaaagatg tatgcgtgtg 281 tcttaatgaa taaggtgtta ttgtagtatc atttagtcct atttgactct tagcatggtt aaatgacttt 351 ttaacggcat tatgactcaa tttaaacaac ttattatctg tacgttttgg taattttgat aatttagctt 421 taatatgttg tatatccttt tttggtacct ccacaagtct gtccgcgtta actgtttttg ttccacgaag 491 atgtattgta ccctcttttt cgtttagatc gataggcaac atattaatta catcgctgta tcttgcacca 561 gtgatagcta ggatgaataa aaaaatataa ctcgattcgt ctctagattt aaagtattct atcaattgca 631 agtattgttc tatggtgatg aatttagagt gttcgtcttt tgattttttt gtaccacgaa tatctatttg 701 atagctaggg tctttcttta aatagccctc atatactgca tctctgaagc attgtgatee acaactgttt 771 aatttacgaa ccgtttcatt agtacgacct cgaccgaatt cgttcaaaaa cttttgatac tccgaacgtt 841 tgatgttttt tattaaaeaa tcactcccga aatattcgtt aaateatttt aatgaacgtt gataccaata 911 gaattgttgt gaagcgacat gtttcttatt ttttgaatct aaccaatcat tgtaatattc ttcaaacttt 981 ttattttcat ctaaattgtt tccatcatcc aaatctctaa gcagttgttg agcagcgttg gttgcctcag 1051 ctttagtttt gaatcctgac tttcttttct ttcctgattt gaaagacgga tgttttacgt cgtactgcca 1121 agatgctgtt gctttattct tcctttttgt aattgtaaat gacgccattt tacttttcct cctcaaaatt 1191 ggcaaaaaat aataagggta ggcgagctac ccgaaatttt attgttgaac aactattgct tcacttcttg 1261 cttttcctac ttcttttcta aaactatcat atgattgatt agggtgtgtt aacgacattc ctggaccacc 1331 tccagcatgt tggtttttgt ccggattatt ttccatttct tcagtggctc ttttagcatt taaatattct 1401 tcgtaactag gttcgtttgg gtcgcgtggt tgtgcttgtt gtccattatt ggtagctgga agattcttct 1471 gtacctgttg cttagatgtg ttattggttt gttgattgtt gttaatgttt gtgttgttct cgttgtttac 1541 ttgattattg ttatcgtttt gattactatt ttcttttttc gcttctgctt tatctttagt ttctttcttt 1611 ttgtctttgt tctctttctt tgtttcggtt ttcttgcttt cctctttctt atcgccgtcg ttgctaccgc 1681 atgcacctaa cactaacgca ctagctaata ataaaactaa taatcttttc atgttttaca ctcctttatt 1751 tgctatttgt tttaataaat ctatgatttc attgttttgt tctatgattt tgttttcatt tttaagatgt 1821 tcgtctaaca tctctattaa gacgaaattt tgatttatca tttcgtaagt aaacatttga cctgtgttgt 1891 taggattaga aaacgaacta ctgaaacgcg ttgaaaagct atctataaat tgaccaactt tattttttae 1961 taacatatct ttaccgctct cagacattgt atttagttcg cgcttattta aagttttttc tataattttg 2031 tattttgttt cctgatttct ttcgatttct tctacttcaa aagggatatt gttattaaat ttttcgataa 2101 tatcacgttt ttcagaaact gacatacgat caaatacttg tttttgacct ttatttaact tccctcgaat 2171 ttttccggca gtccaagact ctttaactgt taacttatca tteggaactt gattcatctt ttatatgact 2241 ccttttctca tatttcttta tatttaaaaa ctctcaacgg ctcaaatgta atcgaatact cgccatagtg 2311 agttccaata ccgtatatct tcttatattg ttctattgcc tccaatatgt attcttcgct taattgtaga 2381 tactcagaca actcatacaa gttacgtacg ccataattgt aagcttctac aatttcgcgt aacgggactg 2451 ctgagataaa gccgtgtcgt cttgcgtaat tttcgaactt gcgattgttg aatttcgatt gatctaaaat 2521 gttgccatac gtcaacttgt ggtgggcaag ttcttcatat aatacttcta atttgttcct ttcggataag 2591 gaaggtctaa taaaaatttc tccttcttga taccaaccat cgaatcctcg aggtactctt tgtgtttctt 2661 tcacttcaac ttcacatttc ataagcaatt cttcgtattt tcccatgcgc caaacccctt tggtgtctta 2731 tttctttcta tctctaaccc attgcataaa attttcgatt tcttcccatt cttcgggagt aaattcatct 2801 ttatttgcat gaccggctat agtttcttga tgaatacttc tttcttctgt aattctcgat ttaggtacat 2871 taaagtaatc tgctaattgt tggacttttg atattctagg atatttaagt tctttaagcc agttagagat 2941 tgttgattga cttaccccga ttgcttcaga caattctact tgagtaatgt tgttctcttt cataagttgt 3011 tctaagttct ctgataaaat ttttctagca ctcttatatt ccataatttt ctcctttagt attacttaat 3081 gtaatactaa tttaccataa gtaatatcac ttttcaatac aaaatattac ttttttgaa taaatatcac 3151 tttaggtgtt gacatattac tttaagtgat agtatagttg taaatgtcaa cgggaggtga tacgaaatgc 3221 cagaaaattt taaagcgttc tctgtaaagg tctggagaac taattcgaat atgacacaac aegatgtcgc 3291 tgataeetta ggcgttacta aacaatctgt aataagatgg gaaaaagatg acgcagaatt aaaaggctta 3361 caattgtatg ctttagccaa attattcaac acagagttg attatataaa ggctaaaaaa atttaacatt 3431 aatatcactt taagtgataa aggggaaac tgaaatgcaa gaattacaaa catttaattt tgaagaatta 3501 ccagtaagga aaattgaagt ggtaggagaa cccttctttt taggtaagga tgttgctgaa attttagggt 3571 atgcacgagc agattacgcc atacgcaatc atgttgatag tgaagatagg ctgatgcacc aaattagtgc 3641 gtcaggtcaa aacagaaata tgatcatcat caacgaatct ggattataca gtttaatctt tgacgcttct 3711 aaacaaagta aaaacgaaaa cattagagc accgctagga aattcaeacg ctgggtaact tcggaagttt 3781 taccgacgtt aagaaaaact ggtgcttacc aagtacctag tgacccaatg caagcattga gattaatgtt 3851 tgaagctaca gaagaaecaa eacaagaaat taaaaacgtg aaagatgatg ttattgattt gaeagaaaat 3921 caaaaactgg atgcgggaga ctacaatttc ttaactagaa caatcaatca aagagtagct catatacaaa 3991 gactacatgc gataacaaac caagaacaac gtagcgaatt attcagggat attaattcag eagtgaaaaa 4061 gatgactggt gcgagttcaa gaacgaacgt aagacaaaaa catttcgacg atgtaattga aatgattgct 4131 aattggttcC cgtcacaagc tactttatat agaatcaagc aaattgaaat gaaattttaa aacgaaatat 4201 aggagaggct gaatatggaa tacatcggat atgcagacgc aaatgcgttt gtaaaaataa gtggcatttc 4271 aaaagatgat ctagagaaa aagtctactc gaacaaagag tttcaaaag aatgcatgta cagatttggt 4341 cgaggacaaa agcgttatat aaaaattgac aaagctattc aatttatcgg taccaattta etgattaatg 4411 aatacgaatt ataggaggag ttatcaaatg agtaaaactt ataaaagcta cctagtagca gtactatgct 4481 tcacagtctt agcgattgta cttatgccgt ttctatactt cactacagcg tggtcaattg caggattcgc 4551 aagtatcgca acattcatat actacaaaga atacttttat gaagaataaa aaaactgcta cttgcgtcaa 4621 caagtaacag tgacaaacat ttatcaaaat atacaactta attaaatcaa aatatacgga ggtagtcaac 4691 tatggctgaa aatattaaaa ctgaacaaca ttattacact aaagatttct caggatacag aaatgaagaa WO 00/32825 PCT/IB99/02040 191 4761 gataactttg tagcaaatca agaattgaca gtaacaatca cattgaacga gtacagaaaa cttattgaaa 4831 taaaggctgt taaagataaa gaagaagata crtacagagg taagtatttt gcggaagaaa gaaaaaacga 4901 aaaattggaa aaagaaaata taaaactaaa aaacaaaatt tatgaattac aaaacgaaga agataacgag 4971 gaggacgaag aagacaagga ggacgagaac gatgtattac aaaattggtg agataaaaaa caaaattata 5041 agctttaacg ggtttgaatt taaagtgtct gtgatgaaga gacatgacgg tatcagtata caaatcaagg 5111 atatgaataa tgttccactt aaatCgtttC atgtcataga tttaagcgaa ctatatattg cgacggatgc 5181 aatgcgtgac gttataaacg aatggattga aaataacaca gatgaacagg acaaactaat taacttagtc 5251 atgaaatggt aggaggtatg aaaagtgaat gatttacaag agagagaatt agaaacattc gaacaagacg 5321 accgattcaa agtaactgat ctagacagtg ctaactgggt ttttaagaaa ctggatgcaa tcacaactaa 5391 agagaatgaa atcaacgatt tagcaaataa agaaattgaa cgcataaacg aatggaaaga taaagaagta 5461 gaaaaattac agagtggcaa agaatattta caaagccttg taattgaata ttacagaata caaaaagaac 5531 aagatagcaa attcaagttg aatacacctt acggaaaagt gacagccaga aaaggttcaa aagtcattca 5601 agttagcaat gagcaagaag tcattaaaca acttgagcaa cgaggttttg acaactatgt aaaagtaact 5671 aaaaaactta gccaatcaga cattaagaaa gatttcaatg taactgaaaa cggcacattg attgacgcaa 5741 acggcgaagt tttagagggt gctagcattg tggagaaacc aacgtcatac acggtaaagg tgggagaata 5811 gatgactgaa aaaactaatc aagatgtcga tattttaacg caactaggtg taaaagacat cagcaaacaa 5881 aatgcaaaca agttttataa atttgcgata tacggcaagt tcggtactgg taaaactacg tttttaacaa 5951 aagataacaa taccttagta ctagatataa atgaggacgg aacaacggta acagaagatg gggcagttgt 6021 gcagattaag aattataagc attttagtgc agtgattaaa atgctgccta aaattattga acaactaaga 6091 gaaaacggaa aacaaattga tgttgtagtg attgaaacaa tccaaaagtt acgtgatatc actatggacg 6161 acatcatgga cggtaaatca aagaaaccga catttaatga ttggggcgag tgtgciacac gcattgtaag 6231 tatttatcgt tatatttcta aattacaaga acattatcaa tttcatcttg ctataagcgg acacgagggc 6301 attaacaaag acaaagatga tgagggaagt actatcaatc caacaatcac gatagaggca caagaccaaa 6371 taaaaaaagc agtcatcagt caatctgacg tgttagcaag aatgacaata gaagaacatg agcaagacgg 6441 cgaaaaaact tatcaatatg tacttaacgc tgaaccatca aatttattcg agacaaagat aagacactca 6511 agcaacatca aaattaacaa caaacgtttc attaatccaa gtattaacga tgttgtacaa gcaattagaa 6581 atggtaatta aaaattaatt aaaaggacgg tataaaaatt atgaaaatca ctggtagaac acaatacatt 6651 caagaaacta atcaagaggc attcatgaaa ggtggggact ttttaggagc tggagaattt acagtaaaag 6721 ttgcaaatgt cgagtttaac gacagagaaa acagatactt cacgattgtt tttgaaaaca acgaaggtaa 6791 acaatacaaa cacaaccaat tcgtcccacc attccaacaa gattatcaag aaaaacaata tatcgagtta 6861 cttagtagat taggaattaa attgaactta ccagatttaa cttttgacac agatcaatta attaacaaaa 6931 tcggaactat tgtacttaaa aataaattta acgaggaaca aggcaagtat tttgtaagac tctcatatgt 7001 aaaagtttgg aataaagacg atgaagtagt taataaacca gaacctaaaa ctgatgagat gaaacaaaaa 7071 gaacagcaag caaatggtaa acagacacct atgagtcaac aatcaaaccc attcgctaat gctaatggtc 7141 caatagaaat caatgatgat gatttaccgt tctaggacgt ggtttaaatg caatacatta caagatacca 7211 gaaagacaat gacggtactt attccgtcgt tgctactggt gttgaacttg aacaaagtca cattgattta 7281 ctagaaaacg gatatccgct aaaagcagaa gtagaggttc cggacaataa aaaactatct atagaacaac 7351 gcaaaaaaat attcgcaatg tgtagagata tagaacttca ctggggcgaa ccagtagaat caactagaaa 7421 attattacaa acagaattgg aaattatgaa aggttatgaa gaaatcagtc tgcgtgactg ttcaatgaaa 7491 gttgcgagag agttaataga actgattata tcgtttatgt ttcatcatca aatacctatg agtgtagaaa 7561. cgagtaagtt gttaagcgaa gataaagcgt tattatattg ggctacaatc aaccgcaact gtgtaatatg 7631 cggaaagcct cacgcagacc tggcacatta tgaagcagtc ggcagaggta tgaacagaaa caagatgaat 7701 cactacgaca aacatgtgtt agcactgtgt agacaacatc ataatgaaca gcacgcaatt ggtgttaagt 7771 cgtttgatga taaatatcaa ttgcatgact cgtggataaa agttgatgag aggctcaata aaatgttgaa 7841 aggagagaaa aatgaataag ttactaatag atgactatcc gatacaagta ttaccgaaat tagctgaatt 7911 aatagggtta aacgaagcaa tagtattgca acaaattcat tattggctaa acaactcaaa acataaatac 7981 gatggcaaaa cttggatttt taattcttat ccagaatggc aaaaacaatt tccattttgg agcgagagaa 8051 ctataaaaag gacatttggg agtttagaaa aacaaaattt attgcatgta ggtaactaca acaaggctgg 8121 atttgaccgt acaaaatggt attcaatcaa ttatgaaaca ttaaacaaac tagtggcacg accatcggga 8191 caaaatggcc cgacgatgag gacaaattgg cacgatgcaa gaggacaaaa tgacccgacc aataccatag 8261 actacacaga gactaacaaa catagagaga cagacgacgt ctcaaagtca tttaagtata ttagtaccaa 8331 tttagaaatt atacaaaacc ctttaaaagc agaacagtta gaacacgaaa ttaaatcatt taagcaagat 8401 cagttcgaaa tagtaaaagt cgctaccgat tactgcaaag aaaacaacaa aggtctgaat tacttactaa 8471 ctgtattaaa gaactggaat aaagaaggcg tttcagataa agaaagtgct gaaaacaaat tgaaacctcg 8541 taactctaaa aaagaaacta ctgatgatgt catagcacaa atggaaaaag aattgagtga tgactaatgc 8611 cgatgagcaa aacacaagca ttagaaatta ttaaaaaagt taggtacgta tacaacatcg attttgataa 8681 accaaagtta gaaatgtgga ttgatgtatt aagtcaaaac ggggattatc aaccaactgt aaaagctgta 8751 gatggatata tcaacagtaa caacccgtac ccgcctaacc taccagcaat catgcgtaag gcacctaaaa 8821 aagtatctat tgagccggta gacaacgaaa ccgctacaca ccaatggaaa atgcagaatg accccgaata 8891 tgtcagacaa agaaaaatag cgctagataa cttcatgaat aagttggcag aatttggggg cgataacgaa 8961 tgaattacgg tcaatttgaa attgaaagca caataatcgc tacgctactt aaacaaccgg acgtactaga 9031 aaagataaga gttaaagatt acatgtttac gaacgaaaag tttaaaacct ttttcaatta tgtaatggac 9101 gtcggaaaga tagatcatca agaaatctat ttaaaagcaa ctaaagataa agagttttta gatgcagata 9171 ctataactaa actttacaac tccgatttca ttggatacgg attctttgaa cgttatcaac aagaattatt 9241 ggaaagttat caaatcaaca aagcgaaaga attggtaact gagttcaaac aacaacctac gaaccaaaat 9311 tttaataact tgattgatga actcaaggat ttaaaaacaa ttactaacag aaaagaagac ggaaccaaga 9381 agtttgttga ggagtttgtc gatgagttat acagcgatag ccctaagaag caaattaaga cgggttataa 9451 gctcatggat tacaaaatag ggggattgga gccgtcgcaa ttaatcgtca tcgcagcgcg tccctcagtg 9521 ggtaagacag gttttgcatt aaacatgatg ctgaacatag cacaaaatgg atacaaaaca tctttcttta 9591 gtctcgaaac aactggcaca tcagtattga aacgtatgtt atcaacaatt actggtattg agttaacaaa 9661 gataaaagaa atcaggaact taacgccgga tgacttaaca aagttaacga atgcgatgga taaaatcatg 9731 aaattaggca tcgatatttc tgataaaagt aatatcacac cgcaagatgt gcgagcgcaa gcaatgaggc 9801 attcagacag gcaacaagtt atttttatag attatcttca actgatggat actgatgcga aagttgatag 9871 acgtgtagca gtagaaaaga tatcacgtga cttaaagata atcgctaacg agacaggcgc aatcatcgta 9941 ctactttcac aactgaatcg tggtgtcgag tctagacagg ataaaagacc aatgctatcg gacatgaaag 10011 aatcaggcgg aatagaagca gatgcgagtt tagcgatgct actttaccgt gatgattatt ataaccgtga WO 00/32825 PCT/IB99/02040 192 10081 cgaagatgac agtatcactg gcaaatctat tgttgaatgt aacatagcca aaaacaaaga cggcgaaacc 10151 ggaataattg aatttgagta ttacaagaag actcagaggt ttttcacatg aatataatgc aattcaaaag 10221 cttattgaaa tcgatgtatg aagagacaaa gcaaagcgac ccgattgtag caaatgtata tatcgagact 10291 ggttgggcgg tcaatagatt gttggacaat aacgagttat cgcctttcga tgattacgac agagttgaaa 10361 agaaaatcat gaatgaaatc aactggaaga aaacacacat taaggagtgt taaaaaatgc cgaaagaaaa 10431 atattactta taccgagaag atggcacgga agatattaag gtcatcaagt ataaagacaa cgtaaatgaa 10501 gtttattcgc tcacaggagc ccatttcagc gacgaaaaga aaattatgac tgatagtgac ctaaaacgat 10571 ttaaaggcgc tcacgggctt ctatatgagc aagagctagg attgcaagca acgatatttg atatttagag 10641 gtggcacaat gagtaaatac aatgctaaga aagttgagta caaaggaatt gtatttgata gcaaagtaga 10711 gtgcgaatat taccaatatt tagaaagtaa tatgaatggc actaactatg atcgtatcga aatacaaccg 10781 aaatttgaat tacaacctaa attcgggaaa caaagaccga ttacgtatat agccgatttc tctttgigga 10851 aggaagggaa actggttgaa gttatagacg ttaaaggtaa ggcgactgaa gttgccaaca tcaaagcgaa 10921 gatattcaga tatcagtata gagatgtgaa tttaacgtgg atatgtaaag cgcctaaata cacaggtcaa 10991 gaatggatgg tatatgagga cttagtgaaa gtcagacgta aaagaaaaag agaaatgaag tgatctaatg 11061 caacaacaag catatataaa cgcaacaatt gatataagaa tacctacaga agttgaatat cagcattacg 11131 atgatgtgga taaagaaaaa gatacgctgg caaagcgctt agatgacaat ccggacgaat tactaaagta 11201 tgacaacata acaataagac atgcatatat agaggtggaa taaatgaagt tgaacgaagt attcgcaact 11271 aatttaaggg taatcatggc tagagataac gtaagtgtcc aagatttgca caatgaaact ggcgtatcaa 11341 gatcaactat tagtggatat aaaaacggaa aagctgagat ggttaactta aatgtattag ataaattggc 11411 agatgctcta qgtgttaatg taagtgaact atttactaga aatcacaaca cgcacaaatt agaggattgg 11481 attaaaaaag taaatgtata gaggtggaat aaatgagtat cgtaaagatt aacggtaaac catataaatt 11551 taccgaacat gaaaatgaat tgataaaaaa gaacggttta actccaggaa tggttgcaaa aagagtacga 11621 ggtggctggg cgttgttaga agccttacat gcaccttatg gtatgcgcti agctgagtat aaagaaattg 11691 tgttatccaa aatcatggag cgagagagca aagagcgtga aatggttagg caacgacgta aagaggctga 11761 actacgtaag aagaagccac atttgtttaa tgtgcctcaa aaacattctc gtgatccgta ctggttcgat 11831 gtcacttata accaaatgtt caagaaatgg agtgaagcat aatgagcata atcagtaaca gaaaagtaga 11901 tatgaacaaa acgcaagaca atgttaaaca accggcgcat tacacatacg gcaacattga aattatagat 11971 tttatcgaac aggttacggc acagtatcca cctcaactag cattcgcaat aggtaatgca atcaaatact 12041 tgtctagagc accgttaaag aatggtcatg aggatttagc aaaggcgaag ttttacgtcc aaagagcttt 12111 tgacttgtgg gagggttaac gatggcaacg caaaaacaag ttgattacgt aatgtcatta caggaacaat 12181 tgggattaga agactgtgaa aaatatacag acgaacaagt taaagctatg agtcataaag aagttagcaa 12251 tgtgattgaa aactataaga caagcatatg ggatgaagag ctatataacg aatgcatgtc gtttggtctg 12321 cctaattgtt aaaaggagtg atgaccatga acgatagcgc acgcaaagaa tacttaaacc aatttttcag 12391 ctctaagaga tatctgtatc aagacaacga gcgagtggca catatccatg tagtaaatgg cacttattac 12461 tttcacggac attataaaac gatgtttaaa ggcgtgaaaa agacatttga tactgcigaa gagctcgaaa 12531 tatatataaa gcaacatgat ttggaatatg aggaacagaa gcaaccaact ttattttaga ggagatggaa 12601 ataatggcaa agattaaaag aaaaaagaag atgacgctac tcgaactggt ggaatgggca tggaacaatc 12671 ctgaacaagt tgaaagtaaa gtgtttcaat cagatagaat gggcacgctt ggagaatgta gcgaagtaca 12741 tttttcaact gatgggcatg ggttttatac aaaagtagta acagataaag atatttttac tgtagaaatc 12811 acagaggaag tcactgaaga tactgagttt gattgtctag tagaactaaa cgatattgaa ggttttgaaa 12881 tatatgaaaa tgattcaatc agagagttga tagacggtac ttccagagcg ttttatatac taaacgaaga 12951 taaaactatg acattaattt ggaaagatgg ggagttggta gtatgatgca aacctataaa gtatgtcttt 13021 gtatcaagtt ctttgcatct aaatgtgatt ataaattaaa gaaacattat ttcgtgaaaa gtacgaatga 13091 ggaaaaagcc acgaacatgg tattaaaact gattcgtaaa aagctcccgt tcgaaactgc aagcatagaa 13161 gtcgaaaaag tggaggcaat ataatgatac aaccaacaag agaagaatta attaatttca tgaaaaaaca 13231 tggagctgaa aatgttgact ctatcactga tgagcaaagt gcaataagac actttagagc tcaatcaaaa 13301 gtttttaaag acgaacgtga tgagtacaag aagcaacgag atgagcttat cgaggataia gctaagttaa 13371 gaaaacgtaa cgaagagctg gagaacatgt ggcgcacagt caaaaatgaa ttgcttggaa gatacgaaca 13441 ttactgtttt aaaattagag aactacaccc tgagagcaaa gcgaacagga taggagctct ctatatagga 13511 ggtaaaagca ctgcagatat tatactgtcg cgaatggaag aactagacgg aacaaatgag ttctacgaat 13581 ttttagggca aatggaggca gacacaaatg aataaccgtg aacaaataga acaatcagtg atcagtacta 13651 gtgcgtataa cggtaatgac acagaggggt tactaaaaga gattgaggac gtgtataaga aagcgcaagc 13721 gtttgatgaa atacttgagg gaatgacaaa tgctattcaa cattcagtta aagaaggtat tgaacttgat 13791 gaagcagtag gggttatggc aggtcaagtt gtctataaat atgaggagga gcaggaaaat gagtattagt 13861 gtaggagata aagtatataa ccatgaaaca aacgaaagtc tagagattgt gcaattggtc ggagatatta 13931 gagatacaca ttataaactg tctgatgatt cagttattag cattatagat tttattacta aaccaattta 14001 tctaattaag ggggacgagt gagtggaatg gaaacgatta aaaaatgtgg tgccgcaccc agttatcaaa 14071 aataaaaatt taaagtcggt atacgtaaca aaagataatg tgaaagaggt tcaaaaagaa ttaggtttct 14141 ttgaaatttt taatgaagaa gtgttattaa ctggattttt atcatttcaa aggataccia tttacattat 14211 ttggattaat cctaaatctc ataagacgcc tagatattac tttgctaacg agcatgagat tgaaagatat 14281 tttgaatttt tggaggacga gtaaatgctt gaaatcatcg accaacgtga tgcattgcta gaagaaaagt 14351 atttaaacga cgactggtgg tacgagctag attattggtt gaataaacgc aagtcagaaa atgaacagat 14421 tgatattgat agagtgctta aatttattga ggaattaaaa cgataggaga taacgaataa atgaataatt 14491 taacagtaga tcaattaaaa gaacttttac aaatacaaaa ggagttcgac gatagaatac cgactagaaa 14561 tttaaatgac acagtagcta gtatgattat tgaatttgcg gagtgggtta acacacttga gttttttaaa 14631 aattggaaga aacaaccagg taagccatta gatacacaat tagaigagat tgctgattac ttagctttca 14701 gtttgcaatt aactctgact attgttgatg aagaagattt ggaagagact actgaggtta tggttgattt 14771 gattgaaaat gaagttactt tacctaaact acattcagtt tattttgttc atgtaatgca tacactaaca 14841 gaacaatttg taaaaggtat tgataatagt attgtacaag ttttaataat gccttttttg tacgccaata 14911 cttactatac aatcgaccaa ctcattgacg catacaaaaa gaaaatgaaa aggaaccacg aaagacaaga 14981 tggaacagca gacgcaggaa aaggatacgt gtaaagacat cttagatcga gtcaaggagg ttttggggaa 15051 gtgacgcaat acttagtcac aacattcaaa gattcaacag gacaaccaca tgaacatttt actgctgcta 15121 gagataatca gacgtttaca gttgttgagg cggagagtaa agaaggagcg aaagagaagt acgagaaaca 15191 agttaagata aggagagatg gagatgccaa agaaaacggt aacgattgat gtagatgaaa acttattagt 15261 agtagctagt aatgaaatat cagaactatt atatgaatat gacagtgagt taatgtcagc tgatgaagat 15331 ggcgataata gagatatcga aaaaaaaaga gacgcattaa aacaagctat acaaattatc gataaattaa WO 00/32825 PCT/IB99/02040 193 15401 catgtcgagg aggcagacga tgattaacat acctaaaatg aaattcccga aaaagtacac tgaaataatc 15471 aagaaatata aaaataaaac acctgaagaa aaagctaaga ttgaagatga tttcattaaa gaaattaatg 15541 ataaagacag tgaattttac agtcctatga tggctaatat gaatgaacat gaattaaggg ctatgttaag 15611 aatgatgcct agtttaattg atactggaga tggcaatgat gattaaaaaa cttaaaaata tggattggtt 15681 cgatatcttt attgctggaa tactgcgatt attcggcgta atcgcactga tgcttgttgt catatcgcct 15751 atctatacag tggctagtta ccaaaacaaa gaagtatatc aagggacaat tacagataaa tataacaaga 15821 gacaagataa agaagacaag ttctatattg tgttagacaa caagcaagtc atcgaaaact ctgacttact 15891 attcaaaaag aaatttgata gcgcagacat acaagctagg ttaaaagtag gcgacaaagt agaagttaaa 15961 acgattggtt atagaataca ctttttaaat ttatatccgg tcttatacga agtaaagaag gtagataaat 16031 aatgattaaa caaatattaa gactattatt cttactagcg atgtatgagc taggtaagta tgtaactgag 16101 aaagtatata ttatgacgac ggctaatgat gatgtagagg cgccgagtga cttcgcaaag ttgagcgatc 16171 agtctgattt gatgagggcg gaggtgtcag agtagatgta tagcaaagag tcaattgtta atatgatagg 16241 cacacataaa atgaagtgta atgtattagc tgatgtaata ccggaatatg atagcaattc aattgcacag 16311 tatggcatac aagcaacgtt gccgaaacca caaggggaaa actcaagtaa agttgaagat gttgttgtga 16381 ggcttgagag agcaaataaa aggtatgctc agatgttaaa agaggttgag tttataaatc aatcgcaaca 16451 gagattggga cacgttgact tttgcttctt agagttattg aagaaaggtt ataacaggga tgcgattatc 16521 aagaagatgc ctaactctaa attaaataga aacaacttct tagcgcgccg tgatgagtta gcagaaaaga 16591 tttatctact acagtgacga aaatgacaaa aatgacagaa atgacgaaaa tgacactatt tttaaactgt 16661 gaattaattt tatataattg atttgtaaga attatcttaa gacgtggggt aatagccaca ttagatgttc 16731 tcatcgatgt gattgagaag tgacaaacat ataaaagatg atatgttacg ctattaatca cctactacct 16801 gcctatatgg tgggtagttt aattcttgca ttttgagtca taactatttt cctcctttca catttattga 16871 acgtagctcc tgcacaagat gtaggggcat tttttatatt taaataacta gagtaattaa cgtaaaggcg 16941 tgtgatacag tgaaaacaat tgattaaatt aacaccgaag caagaaaagt ttgtgctagg actcatagag 17011 ggcaagagcc aacggaaagc atatattgac gcagggtatt cgactaaagg taagagtggg gaatatctag 17081 ataaagaagc gagtacactt tttaaaaatc ggaaggtttc cggaaggtac gaaaaattgc gtcaagaagt 17151 agctgaacaa tcaaaatgga cacgccaaaa ggcctttgaa gaatatgagt ggctaaagaa tgtagctaag 17221 aatgacattg aaatagaggg agtgaagaaa gcgacagctg atgcattcct cgctagttta gatggtatga 17291 atagaatgac gttaggtaac gaagttttag ctaaaaagaa aatagaaact gaaattaaga tgcttgagaa 17361 gaagattgaa caaatagata aaggtgacag tggaacagaa gataaaatca aacaacttca cgacgcaata 17431 acggaagtga tcgtcaatga ataaacttaa atctttatat acggacaaac aaattgaaat attgaagcaa 17501 acgcaaaaac aagattggtt tatgttaatt aatcacggag caaagcgtac aggtaaaaca atattaaaca 17571 atgacttatt tttacgtgag ttaatgcgtg tgcgaaagat agcagacgaa gaaggaattg agacacctca 17641 atatatactt gctggtgcaa cattaggtac gattcaaaaa aacgtactaa tagagttaac taacaaatat 17711 ggcattgagt ttaattttga taaatataat tcattcatgt tatttggcgt tcaagtggtt cagacaggtc 17781 acagtaaagt aagtggtata ggagctatac gtggtatgac atcgtttggt gcatatatca atgaagcgtc 17851 gttagcgcat gaagaggtgt ttgacgagat taagtcacgt tgtagtggaa ctggtgcaag aatattggta 17921 gataccaacc ctgaccatcc cgagcattgg ttgttgaaag attatattga aaatacagat cctaaagcag 17991 gtatactgag tcaccaattt aagctcgatg acaataactt tcttaatgat agatataaag agtctattaa 18061 ggcttcaaca ccatcaggta tgttctatga acgtaatatc aacggtatgt gggtgtctgg tgacggtgta 18131 gtatatgccg actttgattt gaatgagaat acgattaaag cagatgaact ggacgacata cctatcaaag 18201 aatactttgc tggtgtcgac tggggttacg agcactatgg atctattgtg ttaataggac gaggtataga 18271 tggtaacttt tattttattg aggagcacgc acaccaattt aagtttattg atgattgggt ggttattgca 18341 aaagatattg taagtagata tggcaatatt aatttttact gcgatactgc acgacctgaa tacatcactg 18411 aatttagaag acatagatta cgtgcaatta acgctgataa aagtaaacta tcgggtgtgg aggaagttgc 18481 taagttgttc aaacaaaaca agttacttgt tctttatgat aatatggata ggtttaagca agaggtattt 18551 aaatatgttt ggcaccctac aaacggagag cctataaaag aatttgatga cgtgttggac tcgttaagat 18621 atgccatata cacacatact aaacctgaac gattaaggag ggggaaatga cattgtataa gttaatagat 18691 gatattgaag cacaaggaat attgcctaag catattgagg ctctaataga gtcacataaa gacgatagag 18761 agagaatggt taatctctat aatagataca agacacatat tgactatgta ccaatattca aacgtcgacc 18831 aattgaagaa aaagaagatt ttgaaactgg tggaaatgta aggcgattag acgtgtctgt taataacaaa 18901 cttaacaact cttttgacag cgaaattgtt gatacacgtg ttggttattt acatggtgtt cctgttactt 18971 atgatttaga tgaaaacgca gaaaaaaacg aaaagttgaa aaagtttata accaactttg ccattagaaa 19041 tagtgttgat gatgaggatt ctgaaatagg taaaatggca gcaatttgcg gatatggtgc taggttagca 19111 tatattgata cgaatggtga tattaggatt aagaatatag atccctataa tgttattttt gttggcgaca 19181 atattttaga acctacatac tcattgcgct acttttatga aaaagatgat gataatggca ctgattatgt 19251 gtacgcagag ttttacgata atgcttatta ttatgtattt cgaggagaag gtattgacgc tttgcaagaa 19321 gttggacgat atgaacattt atttgattac aatccattgt ttggtgtacc taacaacaaa gagatgatag 19391 gagatgctga aaaggttatt cacttaattg acgcatatga tttaacaatg agcgatgcat caagtgagat 19461 tagtcagaca cgtttagcat accttgtgtt acgcggtatg ggtatgagtg aagaaatgat tcaagaaaca 19531 caaaagagtg gcgcatttga gttgttcgac aaagatatgg acgttaaata cttaacaaaa gatgtaaatg 19601 acacaatgat tgagaaccat ttagatcgaa tcgaaaagaa tatcatgcgt tttgcaaagt cagtaaactt 19671 taattctgac gagtttaacg gaaatgtacc tatcattgga atgaaactta aacttatggc tttagagaac 19741 aagtgtatga cgtttgagcg taagatgaca gctatgttga ggtatcaatt caaagttatt ttatctgcat 19811 taaagcgtaa agggtacaac ttggatgatg atagttattt aaacctgata tttaagttca ctcgtaacat 19881 tccagttaat aagttagaag aatcacaagt gctaattaac ctgaagggac aagtttcaga acgaacaagg 19951 ttaggacaat cacaactagt tgatgatgtt gattacgaat tagacgaaat ggaaaaagaa agtcttgaat 20021 ttaatgacaa attacctgac atagatgaag gtgacgcaaa tgacaaatcc caaaataacc aatcagaatg 20091 atattgatga gtatatcgag ggtttaatct ctaaagcaga aaaaccaata gaacaactat ttgctaatcg 20161 acttaaagag ataaaacaaa tcatcgcaga tatgtttgag aaatatcaaa atgatgatgt gtatgtt-aca 20231 tggactgaat tcaataaata caacaggctc aataaggagt taactcgtat aggtacaatg ttgacttatg. 20301 actataggca agtagctaag atgattcaga agtcacaaga agatgcttat atagaaaaat tccttatgag 20371 cctttattta tatgaaatgg cgagtcaaac atctatgcag tttgatgttc cgagtaaaga ggtaatcaaa 20441 tcagctattg aacaacctat tgagttcatt cgtttaatgc caacactaca aaaacatcgt gatgaagtat 20511 tgaaaaagat acgtatgcac attacacaag gtattatgag tggagagggt tactctaaga tagctaaagc 20581 aatacgtgat gatgtcggca tgtctaaagc tcaatcattg cgtgtggctc gtacagaagc aggcagagca 20651 atgtcacaag ctggacttga tagcgcaatg gttgctaaag ataacggttt gaatatgaag aaacgttggc WO 00/32825 PCT/IB99/02040 194 20721 atgctactaa agatacacga acacgtgata ctcatcgtca tttagatggg gaatcagtgg aaatagatca 20791 gaattttaaa tcaagtgggt gtgttgggca ggcgcccaag ctatttattg gtgtaaacag tgcgaaagag 20861 aatattaatt gtcgttgcaa attactttat tatattgatg aaaatgaatt gccaactgta atgagagcac 20931 gtaaagacga tggtaaaaat gaagttatcc cattcatgac ttatcgtgag tgggagaaat ataagcgaaa 21001 aggtggtaat tgatatggat tttaaaataa aagtaaatgt tgatactggc gaagctatag aaaagttaga 21071 acgcattaaa tccttgtacg aagagataat agagttacaa aacgaaaaag ttgttgtaaa cgtaacagtt 21141 aaaaatgaag ctgatttaga tatggttaaa acatctatta gcgaagaaaa tgctaaaaat aatgatttca 21211 cactttttta gttgtctctt tgctactcga ccttagcatg tcgttaaact gctttttatt atgcactttt 21281 cggactgtta gggtacgcga agggcaaaaa ggagttttga tatatgaata tcgaagaagt taagtctttt 21351 tttgaagaac acaaagacga taaagaagta aaagattatc taaagggact taagacggtg tctgttgatg 21421 acgttaaagg ctttttagat acagaagaag gtaaacgatt cattcaacct gaattagatc gttatcattc 21491 gaaaggatta gaatcatgga aagagaaaaa tcttgaggat ctaatcgaac aagaagtacg gaagcgtaat 21561 cctgagcaat cagaagaaca aaaacgtatt agtgctcttg aacaagagtt agaaaaacgc gacgcagagg 21631 caaaacgtga gaagttaaga agtaacgcgc taggtaaagc gcaggaacta aatttaccaa catccttagt 21701 tgatagattt ttaggcgatt ctgatgaaga tactgagcaa aacttaaaag ctttaaaaga aacctttgac 21771 aagtatgttc aaaaaggcgt tgagtctaaa tttaaatcga gtggaagaga tgttaaagaa tcacgaaatc 21841 aagatttaga cccttcaaat gtaaagtcca ttgaagaaat ggcgaaagaa atcaatatta gaaaataaag 21911 tgaggtaata aaatatggca actccaacat acacgccagg caatgttatt ttatcggatt ttaaaaacgg 21981 cgttattcca gcagaacaag gtactttaat catgaaagac attatggcta attcagcaat tatgaaatta 22051 gctaaaaatg agccaatgac agcacaaaag aaaaaattta cttacttagc aaaaggtgta ggcgcctact 22121 gggtatcaga aacggaacgt attcaaactt ctaagcctga atatgcgcaa gcagaaatgg aagctaagaa 22191 aattggtgta attattccgt tatcaaaaga gtttcttaaa tggactgcaa aagatttctt taatgaggtt 22261 aaacctctaa ttgcagaggc attttacaaa gcgtttgacc aagctgttat ctttggtact aaatcacctt 22331 acaacacttc aactagtggt aaaccgcttg ttgaaggcgc agaagagaaa ggtaacgttg ttacagatac 22401 taataattta tacgtagacc tttcggcatt aatggctact attgaagatg aagagttaga tccaaacgga 22471 gtattaacta cacgttcatt cagaagtaaa atgcgtaatg ctttagatgc taatgacaga ccattatttg 22541 atgctaacgg gaacgagatt atgggattac cactatctta tactggagcg gatgtatacg acaaaaagaa 22611 atcgttagca ctaatgggtg attgggatta cgcacgttac ggtatcttac aaggtattga gtatgcaatt 22681 tctgaagatg ccacgttaac gacgttacaa gcatcagatg cttctggcca accagtatca ttatttgaac 22751 gtgatatgtt cgctttacgt gcgacgatgc atattgcata catgaacgtt aaaccagaag cgttcgcaac 22821 gcttaaacca actgaatagg aggagatatg atggctaatc ctgcagaaga gattaaggta aaaaaagaca 22891 atatgactat tactgttaca aagaaggcat ttgactctta ttacagtctt gtcggttaca aagaggttaa 22961 atcacgtcgt actacgtctg ataagagcga gtgataaaaa tgactcttta tgaagatgtt aaacttttac 23031 tcaagaaaaa tggagtggaa gttaaaagtg atgaagaaga aatatttaag atggaagttg acggaatact 23101 agaagatgtt agggatataa caaacaatga ttttatgaaa gatggtcaag tcatttatcc ttactcaatc 23171 aaaaagtatg tcgcagatgt cctagagtat tatcaacgac ctgaagttaa aaagaattta aagtcaagaa 23241 gtatggggac agtgtcgtac acttataacg atggtgtccc tgattacatt agtggagtat taaacaggta 23311 taaacgagca aagtttcatc cgtttaaacc aataaggtag aggtgttgtt tgtgtttaac ccatacgacg 23381 aattccctca cactatttct attggaagta tcaaaaaagt aggagagtat ccaattatac aagagcgctt 23451 tgtaagcgat aaaacaatta aaggatttat ggatacgcct actacatctg aacaactaaa atttcatcaa 23521 atgtcacaag aatatgacag aaacctatat gtaccttatg acttgccaat atctaaaaac aatttatttg 23591 agtatgaggg tagaatcttt agtattgaag gtgattctgt agatcagggc ggacaacatg aaattaagtt 23661 actacgactt aagcaggtgc catatggcaa aagttaagta cggtgctgat agcatggttg ttgaattgga 23731 taagttcgat aagaaaatag aagagtgggt taaaaaaggt attgctaaaa caacgacgaa gatttacaac 23801 actgctgtag cattagctcc tgttgactta ggttttttag aagaaagtat tgactttaaa tatttcgatg 23871 gtgggttatc cagtgttata agtgtcggcg cagattatgc aatatacgtt gaatacggta ctggtatata 23941 tgctactggt cctggtggta gtcgtgctac aaagattccg tggagtttta aaggtgatga cggcgaatgg 24011 tacaccacat atggtcaagc gccacagcca ttttggaacc ctgcaattga cgcaggacgc aagacattcg 24081 agcagtattt ttcatagagg tggttaaata tgtgggtatc agttgagcct gaacttacaa atcaaatata 24151 taaaagatta atctcagacc ctaacattaa caaactagtt gatgataggg tttttgacgt tgttcaagat 24221 gacgctgttt acccatatat tgttgtgggt gaatcaaacg tcactaacaa cgaatctagc gcaacaatga 24291 gagaaacagt cggtattgtc atacatgtgt attcacagtt cgctacacaa tacgaggcta agctcatttt 24361 aagcgcgata ggttatgtgc ttaacagacc tatagaaata gataattacg agtttcaatt tagccgtatc 24431 gatagtcaag cagtattccc tgatatagac aggtttacta agcatggcac gatacggctt ttatttaagt 24501 acagacataa aaagaaaaac gaaggagtgt attaaatggc gcaaaaaaac tatttagcag ttgtacgtcc 24571 agctgaaact gacttagatc cagtagaatc tttattatta gctgacttac aagaaggtgg acatacgatt 24641 gaaaatgatt tagctgaaat agtacgaggc ggtaaaacgg actattctcc caatgcaatg tcagaatcat 24711 ttaaattaac aattggtaat gtgcctggag ataaaggaat tgaagcagtg aaacacgctg tacaaacagg 24781 tggacagttg cgtatatggc tttatgagcg taataaacgt gcagacggta aacatcacgg aatgtttggt 24851 tatgttgttc cagaatcatt tgaaatgtca tttgatgatg aaagtgacaa aatcgaacta tcattaaaag 24921 ttaaatggaa tacagcagaa ggtgctgaag ataacttgcc gaaagagtgg tttgaagctg caggtgcgcc 24991 tacagttgaa tacgaaaaat tcggcgaaaa agtcggaaca ttcgagaatc aaaagaaagc tagtgttgta 25061 tctgattcac acacggaaga ccattctatg taaactaata gatcaagggg gcgtaagctc cctatttttt 25131 tataaaaaaa ttgaaaagag gtatatattt tgactgaatt taatccaatt acaacattaa aaattaatga 25201 cggagaaaaa gattacgaag tagaagcaaa agtaacattt gcatttgacc gaaaagctga aaaattctca 25271 gaagatagcg aagatgggag aaaaggagca atgccaggat tcaatgttat ctttaacggt ttgctagaat 25341 ctagaaacaa agcgatttta caattttggg aatgtgctac tgcttattta aaaaacccac caactcgaga 25411 acaattagaa aaagcaattg atgatttcat cactgaaaac gaggatactt tgccgttatt acaaggggct 25481 ttggacaaac ttaacaatag tggttttttc aagagggaga gtcgctcgta ctggatgaca ttgaacaaag 25551 caccgaatat ggccaaaagc gaggacaaag aaatgacgaa agcaggcata gaaatgatga aagagaatta 25621 caaggaaatc atgggcgcag aaccttacac gattactcaa aaataaggca actgacagct agatatttag 25691 gatatatccc tgaacatgaa ttgttagcac taacacctgc tgaatggcgt gattggctta ttggtggtca 25761 ggataggtac ctagatcaaa gacaattatt aattgaacaa gcgcaagcta acggcttagt acaagcttct 25831 aagaggctaa ctagtatgat tcgtgacatt gagaaacaac gttacgaaat aagagaacct ggtagctatg 25901 ctcgtgtaca aaaagctaga ttagaagaag aaaaaagaag acgtgaactc ttcaaagaag gtacaagaaa 25971 attccttgaa tcgaaaggag gttagcCttt ggatactcat tttatggcaa agattatggc caatattaga WO 00/32825 PCT/IB99/02040 195 26041 gatttccaaa gcaacgtaag gaaagctcaa cgattagcaa agacgtctgt accaaacgaa attgaaacag 26111 atgtaaaagc agatatttca agattccaaa gagctttaca acgcgctaaa tcaatggctc aacgatggcg 26181 agagcattct gttaaattat tCatgaaaac agatgagtat aaagcgaatt tagaacgcgc taaagctcaa 26251 gtagagcgat ttaaacaaca taaagtagat ttgaaactaa gtaacactga attaatggcc aaatataatg 26321 caactaaagc tactgtcgaa gcttggagaa aacatgttgt taagttggat ttagatgcaa accccgctaa 26391 aatggcggtt aaagggttta aagaagattt aatagatctt agcaggcata gttttgatat tgattccagc 26461 agatggaaat taggaaataa attcacaaaa gaattcaatg aagtcgaagg agcagttaaa cgttctttcg 26531 gaagaattgg tcagattatg agaaaagaag taaatggaac aagtgatatt tggggtaaac ttaacaactc 26601 attgaaagat tacggcgaga aaatggacgc cttagctact aaaatccgaa ctttcggtac tatcttcgcg 26671 caacaggtca aaggcttaat gattgctagt atacaagcat tgataccagt gattgccgga ttagtacctg 26741 caataatggc agtacttaat gcggttggtg tattaggtgg tggcgtttta ggtttagttg gcgcattctc 26811 tgtcgcaggt cttggagttg ttggCtttgg tgcaatggct attagcgctc ttaaaatggt tgaagatgga 26881 acattggcag taacaaaaga agttcaaaac tttagagatg cgagcgatca gttaaaaact acatggcgtg 26951 atattgttaa agagaatcaa gcaagtatct ttaatgcgat gtcagcaggt atcagaggcg ttacaagtgc 27021 gatgtctcaa ttaaaaccat tcttatccga agtatctatg ctagttgaag caaacgcacg cgagtttgag 27091 aattgggtta aacattccga aacagctaag aaagcgtttg aagcattgaa tagcataggt ggcgcaatct 27161 tcggagattt attgaacgct gcaggacgat ttggcgacgg attagttaac attttcactc aattaatgcc 27231 gttgttcaaa tttgtgtctc aaggactaca gaacatgtct atagctttcc aaaattgggc taatagtgta 27301 gctggtcaga atgctattaa agcgtttatt gactacacta ccactaactt acctaagatt ggtcagatat 27371 ttggtaatgt gttcgctggt attggtaatt taatgattgc ttttgcacaa aacagttcca acatttttga 27441 ttggttggtt aaattaactt ctcaatttag agcatggtca gaacaagtag gacaatcaca agggtttaaa 27511 gactttatca gttatgttca agagaatggt cctactatta tgcagttaat cggtaatatc gtaaaagcat 27581 tagttgcttt tggtactgca atggctccta tagctagtaa attgttagac tttatcacta atctagctgg 27651 atttatcgct aaactattcg aaacacaccc agctatagca caagttgctg gcgttatggg tattttaggc 27721 ggtgtatttt gggctttaat ggCtCcgatt gttgctataa gtagtgtact tacaaatgtg tttggtttga 27791 gcttattcag cgtcactgaa aagattttag acttcgttag aacatcaagt ttagttactg gagctacgga 27861 agcattaata ggtgcattcg gttcgatttc agcacctatt ttagcagttg ttgcagtaat tggtgcattc 27931 attggtgtcc tcgtttattt atggaaaaca aacgagaact ttagaaatac tattactgaa gcgtggaacg 28001 gtgttaaaac ggcagtttct ggtgcgattc aaggtgtagt cggctggtta actgaattgt ggggcaaaat 28071 ccaatctacc ttacaaccga taatgcctat attgcaagta ttaggacaaa tattcatgca agttttaggt 28141 gttttggtaa taggcatcat tacaaacgtt atgaatatca tacaaggttt gtggacttta attacaattg 28211 cgttccaagc cataggaaca gtgatatccg tagcagtcca aatcatagta ggtttgttca ctgctttaat 28281 tcagttgctt actggcgact tctcaggtgc ttgggagact attaaaacta cggttaccaa tgtgcttgat 28351 acgatttggc aatacatgca atcagtttgg gagtcaatta tcggcttttt aactggcgta atgaatcgaa 28421 cactttctat gtttggtaca agttggtcac agatatggag tacaatcact aattttgtta gcagtatttg 28491 gaacactgtt acaagttggt tcagtcgagt ggcttcgagt gtagctgaaa aaatggggca agcactaaac 28561 tttattatca caaaaggttc tgaatgggtt tctaacattt ggaatacagt tacaagtttc gcgagtaaag 28631 tagctgatgg gtttaaaaga gttgtctcaa atgtaggtga cggtatgagt gatgcacttg gtaagattaa 28701 aagtttcttc agtgatttct taaatgccgg agcggaatta atcggcaaag tagctgaggg tgtagccaaa 28771 tctgcgcaca aagtagtcag cgcggtaggc gatgcgattt catcagcttg ggactctgta acttcattcg 28841 taagtggaca cggtggaggt agtagcttag gtaaaggttt agcggtatca caagcaaaag taattgctac 28911 agactttggc agtgccttta ataaagagct atcctctact ttgacagata gtatagtaaa tcctgtaagt 28981 acttctatag acagacacat gactagcgat gttcaacata gcttaaaaga aaataataga cctattgtga 29051 atgtaacgat tagaaatgag ggcgaccttg atttaattaa atcacgcatt gatgacatga acgctataga 29121 cggaagtttc aacttattat aagggaggtt tgttagttga tagcgcacga tatagaagta ataaggaatg 29191 gttcacagta tcgcgtcagt gacaatcctt tcacttataa tcacttggaa gtagttgaat ataacgttac 29261 aggcgcagga tatcatcgta actattctga tatagagggt attgatggta gatttcataa ttacgctaaa 29331 gaagaactta aaaaagtaga gcttaagata aggtataaag tacctaaaat tgcttatgct tcacatttaa 29401 agtcagacgt ccaagcacta tttgctggac gtttttattt aagggaatta gctacaccag acaattcaat 29471 taagtatgag catatattag atataccaaa agacaaacaa gcatttgagc ttgattatgt tgatggacga 29541 caactttttg taggactagt aagtgaagtt tcttttgaca caacacaaac atcaggggaa ttttctttgt 29611 cgtttgaaac aaccgaacta ccatactttg aaagtgtcgg ttatagtact gatcttgaaa gtaataacga 29681 ccctgaaaaa tggtcggtac ctgatagatt gcctacaaac gaaggtgata agaggcgtca aatgacattt 29751 tacaacacta actcaggaga agtttattat aacggtgatg ttcctttaac acagtttaat cagtttaatg 29821 ttgttgaaat agagitagct gaagatgtta aagctaatga taaggatgga ttcactttct atacagataa 29891 aggaaatatc tcagttatta aggaagttga tttaaaagcc ggagataaaa taatcttcga cggtaaacat 29961 acctatagag gttatttaaa tatagattct tttaataaaa ctttagaaca accggtttta tatccaggct 30031 ggaatcgatt caagtctaat aaagtaatga aacaaattac atttagacac aaattatatt ttagataagg 30101 agtagcctat gccaatttta ttaaaaagtc tacagggtgt agggcacgct attaatgtta gtacaaaggt 30171 aagtaaaaag ctaaatgaag atagttcttt ggatctaact attatcgaga acgcgagtac gtttgacgca 30241 ataggtgcta taactaaaat gtggacgatc actcatgttg aaggtgaaga tgatttcaac gaatatgtaa 30311 ttgtcatact tgataagtct actattggcg aaaaaataag gcttgatatc aaagctaggc aaaaagaact 30381 tgatgacctt aacaattcta ggatttacca agagtataac gaaagtttta caggcgttga gttcttcaat 30451 actgtcttta aaggaacggg ttataagtat gtattacatc caaaagtaga tgcatctaaa ttcgagggat 30521 taggcaaagg agatacacga ttagaaatct ttaaaaaagg acttgagcgt tatcatctcg aatatgaata 30591 cgatgcaaag actaaaacgt ttcatttgta tgatgaatta tctaagtttg ccaattatta cattaaagct 30661 ggtgtgaatg ctgataacgt caaaatacaa gaagatgcat ctaaatgtta tacctttatt aaaggttatg 30731 gtgattttga tggacaacag acttttgcag aagcgggact acaaattgaa ttCactcatc cattagcaca 30801 attgataggt aaaagagaag cgccaccgct tgttgatgga cgtattaaaa aagaagatag tttaaaaaaa 30871 gcaatggagt tattgataaa gaaaagtgtc actgcttcta tttccttaga ctttgtagcg ttacgtgaac 30941 atttcccaga agctaaccct aaaataggtg atgttgttag agtggtggat tctgccatag gatataacga 31011 cttagtgaga atagtcgaaa tcactacaca tagagatgcg tacaataata tcactaagca agatgtagta 31081 ttaggagact ttacaaggcg taatcgttat aacaaagcag ttcatgatgc tgcaaattat gttaaaagcg 31151 taaaatctac aaaatccgac ccatctaaag aactaaaagc attaaacgca aaagttaacg caagtttatc 31221 tataaataat gaattggtta agcagaatga aaaaataaac gctaaagtcg ataagatgaa tactaaaaca 31291 gttacaactg ctaatggtac gatcatgtac gactttacta gtcaatcaag tataagaaac atcaaatcaa WO 00/32825 PCT/IB99/02040 196 31361 ttggaacgat tggcgactct gtagctagag ggtcgcacgc aaaaactaat ttcacagaaa tgttaggcaa 31431 gaaattgaaa gctaaaacga ctaatcttgc aagaggtggc gcaacaatgg caacagttcc aataggtaaa 31501 gaagcggtag aaaacagcat ttatagacaa gcagagcaaa taagaggaga cctaatcata ttacaaggca 31571 ctgatgatga ctggttacac ggttattggg caggcgtacc gataggcact gataaaacgg atacaaaaac 31641 gttttacggt gccttttgtt ctgcaattga agttattaga aagaataatc cagattcaaa aatactagtg 31711 atgacagcta caagacaatg ccctatgagt ggtacaacaa tacgccgtaa agacacggac aaaaacaaac 31781 tagggttaac acttgaggac tatgtaaacg ctcaaatatt agcttgtagt gagttagatg taccagtgtt 31851 tgacgcatat cacacagatt actttaagcc atacaatcca gcttttagga aagcgagcat ggaggacggc 31921 ttacacccta acgaaaaagg tcacgaggtt attatgtacg agttaatcaa ggattattac agtttttacg 31991 actaaaggag gcaaccaatg gcttacggat taattacaag tttacattca atgacaggtc ggaaaatagt 32061 tgctcaacat gagtataact atcgcttgtt agatgaaggt atgagcaaac ttgagaaaat gtttatatac 32131 catcaaaaag aagaaatata cgcacactca gcgaaacaaa ttaaatactt gaatgacagt gttgaagatt 32201 atttaacgta tttaaatagc cgttttagca atatgattct aggccataac ggcgacggta tcaatgaagt 32271 aaaagacgcg cgtattgata atacaggtta tggtcataag acattgcaag atcgtttgta tcatgattat 32341 tcaacactag atgctttcac taaaaaggtt gagaaagctg tagatgaaca ctataaagaa tatcgagcga 32411 cagaataccg attcgaacca aaagagcaag aaccggaatt tatcactgat ttatcgccat atacaaatgc 32481 agtaatgcaa tcattttggg tagaccctag aacgaaaatt atttatatga cgcaagctcg tccaggtaat 32551 cattacatgt tatctagatt gaagcccaac ggacaattta ttgatagatt gcttgttaaa aacggcggtc 32621 acggtacaca caatgcgtat agatacattg atggagaatt atggatttat tcagctgtat tggacagtaa 32691 caaaaacaac aagtttgtac gtttccaata tagaactgga gaaataactt atggtaatga aatgcaagat 32761 gtcatgccga atatatttaa cgacagatat acgtcagcga tttataatcc tatagaaaat ttaatgattt 32831 tcagacgtga atataaagct tctgaaagac aagctaagaa ttcattgaat ttcattgaag taagaagtgc 32901 tgacgatatt gataaaggta tagacaaagt attgtatcaa atggatatac ctatggaata cacttcagat 32971 acacaaccta tgcaaggtat cacttatgat gcaggtatct tatattggta tacaggtgat tcgaatacag 33041 ccaaccctaa ctacttacaa ggtttcgata taaaaacaaa agaattgtta tttaaacgac gtatcgatat 33111 tggcggtgtg aataataact ttaaaggaga cttccaagaa gctgagggtc tagatatgta ttacgatcta 33181 gaaacaggac gtaaagcact tttaataggg gtaactattg gacctggtaa taacagacat cactcaattt 33251 attctatcgg ccaaagaggt gttaaccaat tcttaaaaaa cattgcacct caagtatcga tgactgattc 33321 aggtggacgt gttaaaccgt taccaataca gaacccagca tatctaagtg atattacgga agttggtcat 33391 tactatatct atacgcaaga cacacaaaat gcattagatt tcccgttacc gaaagcgttt agagatgcag 33461 ggtggttctt ggatgtactg cctggacact ataatggtgc tctaagacaa gtacttacca gaaacagcac 33531 aggtagaaat atgcttaaat tcgaacgtgt cattgacatt ttcaataaga aaaacaacgg agcatggaat 33601 ttctgtccgc aaaacgccgg ttattgggaa catatcccta agagiattac aaaattatca gatttaaaaa 33671 tcgttggttt agatttctat atcactactg aagaatcaaa acgatttact gattttccta aagactttaa 33741 aggtattgca ggttggatat tagaagtaaa atcgaataca ccaggtaaca caacacaagt attaagacgt 33811 aataacttcc cgtctgcaca tcaattttta gttagaaact ttggtactgg tggcgttggt aaatggagtt 33881 tattcgaagg aaaggtggtt gaataatgat agtagataat ttttcgaaag acgataactt aatcgagtta 33951 caaacaacat cacaatataa tccaattatt gacacaaaca tcagtttcta tgaatcagat agaggaactg 34021 gtgttttaaa ttttgcagta actaagaata acagaccgtt atctataagt tctgaacatg ttaaaacatc 34091 tatcgtgtta aaaaccgatg attataacgt agatagaggc gcttatattt cagacgaatt aacgatagta 34161 gacgcaatta atgggcgttt gcagtatgtg ataccgaatg aatttttaaa acattcaggc aaggtgcatg 34231 ctcaggcatt ctttacacaa aacgggagta ataatgttgt tgttgaacgt caatttagct tcaatattga 34301 aaatgattta gttagtgggt ttgatggtat aacaaagctt gtttatatca aatctattca agatactatc 34371 gaagcagtcg gtaaagactt taaccaatta aagcaagata tggatgatac acaaacgtta atagcaaaag 34441 tgaatgatag tgcgacaaaa ggcattcaac aaatcgaaat caagcaaaac gaagctatac aagctattac 34511 tgcgacgcaa actagtgcaa cacaagctgt tacagctgaa gtcgataaaa tagttgaaaa agagcaagcg 34581 atttttgaac gtgttaacga agttgaacaa caaatcaatg gcgctgacct tgttaaaggt aattcaacaa 34651 caaattggca aaagtctaaa cttacagatg attacggtaa agcaattgaa tcgtatgagc agtccataga 34721 tagcgtttta agcgcagtta acacatctag gattattcat attactaatg caacagatgc gccagaaaag 34791 acggatatag gcacgttaga gaagcctgga caagatggtg ttgatgacgg ttcttcgttc gatgaatcaa 34861 cttatacatc aagcaaatct ggtgtgttag ttgtttatgt tgttgataat aatactgctc gtgcaacatg 34931 gtacccagac gattcaaacg atgagtacac aaaatacaaa atctacggca catggtaccc gttttataaa 35001 aagaatgatg gaaacttaac taagcaattt gttgaagaaa cgtctaacaa cgctttaaat caagctaagc 35071 agtatgtaga tgataaattc ggaacaacga gctggcaaca acataagatg acagaggcga atggtcaatc 35141 aattcaagtt aacttaaata atgcgcaagg cgatttggga tatttaactg ctggtaatta ctatgcaaca 35211 agagtgccgg atttaccagg tagtgttgaa agttatgagg gttatttatc ggtattcgtt aaagacgata 35281 caaacaagct atttaacttc acgccttata actctaaaaa gatttacaca cgatcaatca caaacggcag 35351 acttgagcaa cagtggacag ttcctaatga acataagtca acggtattgt tcgacggtgg agcaaatggt 35421 gtaggtacaa caatcaatct aaccgaacca tacacaaact attctatttt attagtaagt ggaacttatc 35491- caggtggcgt tattgaggga ttcggactaa ccacattacc taatgcaatt caattaagta aagcgaatgt 35561 agttgactca gacggtaacg gtggcggtat ttatgagtgt ttactatcca aaacaagtag cactacttta 35631 agaatcgata acgatgtgta ctttgattta ggtaaaacat caggttctgg agcgaatgcc aacaaagtta 35701 ctataactaa aattatgggg tggaaataat gaaaatcaca gtaaatgata aaaatgaagt tatcggatac 35771 gttaatactg gcggtttacg caatagttta gatgtagacg ataacaatgt gtctatcaaa ttcaaagaag 35841 agttcgaacc tagaaagttc gttttcacta acggcgaaat taaatacaat agcaatttcg aaaaagaaga 35911 cgtaccgaat gcatcaaacc aacaaagtgc gtcagattta agtgatgagg aacttcgcgg aatggttgca 35981 agtatgcaaa tgcagatgac gcaagtgaac atgttgacaa tgcaattgac gcaacaaaac gctatgttaa 36051 cacaacagtt gaccgaactg aaaactaaca aaacaaatac tgagggggac gtttaaatga tgaagatgat 36121 ttatccaact tttaaagaca ttaaaacttt ttatgtgtgg ggttgctata aaaatgagca aattaagtgg 36191 tacgtagaca tgggtgtaat cgacaaagaa gaatatgcat tgatcactgg tgaaaaaiat ccagaggcaa 36261 aagatgaaaa gtcacaggtg taatgcttga ggctttttaa tttaacacaa agtaggtggc gtaatgtttg 36331 gatttaccaa acggcacgaa catgaatggc gaattagaag attagaagag aatgataaaa caatgcttag 36401 cactctcaat gagattaaat taggtcaaaa aactcaagag caagttaaca ttaaattaga taaaacttta 36471 gatgctatcc agagggaaag acagatagac gaaaaaaata agaaagaaaa cgacaaaaat atacgcgata 36541 tgaaaatgtg gattctcggt ttgataggga ctatcttcag tacgattgtc atagctttac taagaactat 36611 ttttggtatt taaaggaggt gattaccatg cttaaaggga ttttaggata tagcttctgg gcgtgcttct WO 00/32825 PCT/IB99/02040 197 36681 ggtttggtaa atgtaaataa cagttaagag tcagtgcttc ggcactggct ttttattttg attgaaatga 36751 ggtgcataca tgggattacc taacccaaag actagaaagc ctacagctag tgaagtggtg gagtgggcaa 36821 agtcgaatat tggtaagagg attaatatag ataattatcg gggcagtcaa tgttgggata cacctaactt 36891 tatttttaaa agatattggg gttttgtaac atggggcaat gctaaggata tggctaatta cagatatcct 36961 aagggtttcc gattctatcg ttattcatct ggatttgtac cggaacctgg agacatcgca gtttggcacc 37031 ctggcaacgg aataggttcg gacggacaca ccgcaatagt agtaggacca tctaataaaa gttattttta 37101 tagcgttgac caaaactggg ttaattctaa tagttggaca ggttctccag gaagattagt aagacaccct 37171 tatgtaagtg ttacaggctt tgttaggcct ccatactcaa aagatactag caaacctagt agtactgata 37241 caagttcagc atcaaaagcc aatgactcaa caattactgg cgaagcgaag aaaccgcaat ttaaagaagt 37311 taaaacagta aaatacactg cttacagcaa tgttttagat aaagaagagc acttcattga tcatatagtt 37381 gtaatgggtg atgaacgctc agatattcaa ggattatata taaaagaatc aatgcatatg cgttctgtag 37451 acgaactgta tacgcaaaga aataagttta taagcgatta tgaaataccg catttatatg tcgatagaga 37521 ggctacatgg cttgctagac caaccaattt tgatgacccg cgtcacccta attggctagt tattgaagta 37591 tgtggtggtc aaacagatag caaacgacaa ttcttattga atcaaataca agcgttaata cgtggtgttt 37661 ggttattgtc agggattgat aaaaacttat ctgaaacgac gttaaaggta gaccctaata tttggcgtag 37731 tatgaaagat ttaattaatt acgacttgat taagcaaggt ataccggata acgcaaagta tgagcaagtt 37801 aaaaagaaaa tgcttgagac atacattaaa cgagatatat tgacacgaga aaatataaaa gaagtaacga 37871 caaaaacaac aataagaatt agtgataaaa catcagttga cagtgcgtcc acacgaggcc ctactccatc 37941 agacgaaaaa ccaagcatcg ttactgaaac aagtccattc acattccagc aagcactgga tagacaaatg 38011 tctaggggta acccgaaaaa atctcataca tggggctggg ctaatgcaac acgagcacaa acgagctcgg 38081 caatgaatgt taagcgaata tgggaaagta acacgcaatg ctatcaaatg cttaatttag gcaagtatca 38151 aggcatttca gttagtgcgc ttaacaaaat acttaaagga aaaggaacgc tcgacggaca aggcaaagca 38221 ttcgcggaag cttgtaagaa aaacaacatt aacgaaattt atttgatcgc gcacgctttc ttagaaagtg 38291 gatacggaac aagtaacttc gctagtggta gatacqgtgc atataattac ttcggtattg gtgcattcga 38361 caacgaccct gattatgcaa tgacgtttgc taaaaataaa ggttggacat ctccagcaaa agcaatcatg 38431 ggcggtgcta gcttcgtaag aaaggattac atcaataaag gtcaaaacac attgtaccga attagatgga 38501 atcctaagaa tccagctacc caccaatacg ctactgctat agagtggtgc caacatcaag caagtacaat 38571 cgctaagtta tataaacaaa tcggcttaaa aggtatctac ttcacaaggg ataaatataa ataaagaggt 38641 gtgtaaatgt acaaaataaa agatgttgaa acgagaataa aaaatgatgg tgttgactta ggtgacattg 38711 gctgtcgatt ttacactgaa gatgaaaata cagcatctat aagaataggt atcaatgaca aacaaggtcg 38781 tatcgatcta aaagcacatg gcttaacacc tagattacat ttgtttatgg aagatggctc tatattcaaa 38851 aatgagcccc ttattatcga cgatgttgta aaagggttcc ttacctacaa aatacctaaa aaggttatca 38921 aacacgctgg ttatgttcgc tgtaagctgt ttttagagaa agaagaagaa aaaatacatg tcgcaaactt 38991 ttctttcaat atcgttgata gtggtattga atctgctgta gcaaaagaaa tcgatgttaa attggtagat 39061 gatgctatta cgagaatttt aaaagataac gcgacagatt tattgagcaa agactttaaa gagaaaatag 39131 ataaagatgt catttcttac atcgaaaaga atgaaagtag atttaaaggt gcgaaaggtg ataaaggcga 39201 accgggacaa cctggtgcga aaggtgatac aggtaaaaaa ggagaacaag gcgcacccgg taaaaacggt 39271 actgtagtat caatcaatcc tgacactaaa atgtggcaaa ttgatggtaa agatacagat atcaaagcag 39341 aacctgagtt attggacaaa atcaatatcg caaatgttga agggttagaa gataaattgc aagaagttaa 39411 aaaaatcaaa gatacaactc tcaacgactc taaaacgtat acggattcaa aaattgctga actagttgat 39481 agcgcgcctg aatctatgaa tacattaaga gaattagcag aagcaataca aaacaactct atttcagaaa 39551 gtgtattgca acagattggc tcaaaagtta gtacagaaga ttttgaggaa ttcaaacaaa cactaaacga 39621 tttatatgct ccaaaaaatc ataatcatga tgagcggtat gttttgtcat ctcaagcttt tactaaacaa 39691 caagcggata atttatatca actaaaaagc gcatctcaac cgacggttaa aatttggaca ggaacagaaa 39761 atgaatataa ctatatatat caaaaagacc ctaatacact ttacttaatt aaggggtgat ttttatggaa 39831 ggtaatttta aaaatgtaaa gaagtttatt tacgaaggtg aagaatatac aaaagtatat gctggaaata 39901 tccaagtatg gaaaaagcct tcatcttttg taataaaacc cttacctaaa aataaatatc cggatagcat 39971 agaagaatca acagcaaaat ggacaataaa tggagttgaa cctaataaaa gttatcaggt gacaatagaa 40041 aatgtacgta gcggtataat gagggtttcg caaactaatt taggttcaag tgatttagga atatcaggag 40111 tcaatagcgg agttgcaagt aaaaatatca actttagtaa tccttcaggg atgttgtatg tcactataag 40181 tgatgtttat tcaggatctc caacattgac cattgaataa ttttaaacga ctaatttttt agtcgttttt 40251 tattttggat aaaaggagca aacaaatgga tgcaaaagta ataacaagat acatcgtatt gatcttagca 40321 ttagtaaatc aattcttagc gaacaaaggt attagcccga ttccagtaga cgatgagact atatcatcaa 40391 taatacttac tgttgttgct ttatatacta cgtataaaga caatccaaca tctcaagaag gtaaatgggc 40461 aaatcaaaag ctaaagaaat ataaagctga aaacaagtat agaaaagcaa cagggcaagc gccaattaaa 40531 gaagtaatga cacctacgaa tatgaacgac acaaatgatt tagggtaggt gttgaccaat gttgataaca 40601 aaaaaccaag cagaaaaatg gtttgataat tcattaggga agcagttcaa tcctgatttg ttttatggat 40671 ttcagtgtta cgattacgca aatatgtttt ttatgatagc aacaggcgaa aggttacaag gtttatacgc 40741 ttataatatt ccatttgata ataaagcaag gattgaaaaa tacgggcaaa taattaaaaa ctatgatagc 40811 tttttaccgc aaaagttgga tattgtcgtt ttcccgtcaa agtatggtgg cggagctgga catgttgaaa 40881 ttgttgagag cgcaaattta aacactttca catcatatgg gcaaaattgg aatggtaaag gttggacaaa 40951 tggcgttgcg caacctggtt ggggtcctga aactgttaca agacatgttc attattacga tgacccaatg 41021 tattttatta gattaaattt cccagataaa gtaagtgttg gagataaagc taaaagcgtt attaagcaag 41091 caactgccaa aaagcaagca gtaattaaac ctaaaaaaat tatgcttgta gccggtcatg gttataacga 41161 tcctggagca gtaggaaacc gaacaaacga acgcgatttt atccgtaaat atataacgcc aaatatcgct 41231 aagtatttaa gacatgcagg tcatgaagtt gcattatatg gtggctcaag tcaatcacaa gacatgtatc 41301 aagatactgc atacggtgtt aatgtaggaa ataataaaga ttatggatta tattgggtta aatcacaggg 41371 gtatgacatt gttctagaga ttcatttaga cgcagcagga gaaaatgcaa gtggtgggca tgttattatc 41441 tcaagtcaat tcaatgcgga tactattgat aaaagtatac aagatgttat taaaaataac ttaggacaaa 41511 taagaggtgt aacacctcgt aatgatttac tgaacgttaa tgtatcagca gaaataaata tcaattatcg 41581 tttatctgaa ttaggtttta ttactaataa aaaagatatg gattggatta agaagaatta tgacttgtat 41651 tctaaattaa tagctggtgc gattcatggt aagcctatag gtggtttggt agctggtaat gttaaaacat 41721 cagctaaaaa ccaaaaaaat ccaccagtgc cagcaggtta tacacttgat aagaataatg tgccttataa 41791 aaaagagact ggtaattaca cagttgccaa tgttaaaggt aataacgtaa gggacggcta ttcaactaat 41861 tcaagaatta caggtgtatt acctaataac gcaacaatca aatatgacgg cgcatattgc atcaatgggt 41931 atagatggat tacttatatt gctaatagtg gacaacgtcg ctatattgcg acaggagagg tagataaagc WO 00/32825 PCT/IB99/02040 198 42001 aggtaatagg ataagtagtt ttggtaagtt tagcacgatt tagtatttac ttagaataaa aattttgcta 42071 cattaattat agggaatctt acagttatta aataactatt tggatggatg ttaatattcc tatacacttt 42141 ttaacattac tctcaagatt taaatgtaga taacaggcag gtactacggt acttgcctat ttttttgtta 42211 taatgtaatt acattaccag taaccaatct ggcttaaaac cacatttccg gtagccaatc cggctatgca 42281 gaggacttac ttgcgtaaag tagtaagaag ctgactgcat atttaaacca cccatactag ttgctgggtg 42351 gttgtttttt atgttatatt ataaatgatc aaaccacacc acctattaat ttaggagtgt ggttattttt 42421 tatgcaaaaa aaacgaaaaa aagttcataa aaagtattgc atatcacgtt taaccgtgtt ataataaggt 42491 ataccagttg agaggaggat aaaaagtgtt agaaaatttt aaaactatag cagaaatcgc cttttataca 42561 atgtcagcaa ttgccatagc gaaaacattg aaaaaagacg ataagtaagt agacaagccc gaaagggctg 42631 tctatatata aattctaaca ctaaaatact atgaaaacaa tttacattat tttaatcatt cttatttgga 42701 taaacgtgtt tttaggcaac gatataagta aaagtgttgt tgcactgctt actactttac tgcttatcaa 42771 tttatggaag agggataaaa atgacagcaa taaaagaaat aattgaatca atagaaaagt tattcgaaaa 42841 agaaacggga tataaaattg ctaaaaattc cggattacca tatcaaactg tgcaagattt aagaaatgga 42911 aaaacatctt tatcagatgc cagatttaga acgataataa agttatacga gtatcaaaga tcgcttgaaa 42981 acgaagaaga taaataaaag gagccaaaaa tatgtttgtt acaaaagaag aatttaaaac tttgaatgta 43051 aaagaagtat ttgaatcagg taaaaacttt ataaaaatta cagatggaag acatgcaata tattgggtaa 43121 atgatagata cgtagtactt gaccataaaa aaggcgattt gtacccgcaa aaagcatacc caaaatatat 43191 caaaagaaaa ttagtaagtt aaataattag aaaaccacgt cttaattgac gtggttattt tttaggtttg 43261 cgcgtgtcaa atacgtgtca atttagttct atttctttag ttttctttct aaacttaatt gcttgtaaac 43331 cgcatagtta taggcttttc agctatatac caagataaga tttatcccgc cgtctccata aaaatatgct 43401 tggaaacctt gatttaatgg ggttttaatc tagcaagtgt caaatatgtg tcaagaaaat aattttctga 43471 cacgttgacc ttgctctttt ttatgttcat caagtaagtg agagtaggtg tctaaagtta tagatatatt 43541 ataatggcct aatcttttgc taatatattc aatagg WO 00/32825 PCT/IB99/02040 199 Table 10 Bacteriophage 96 ORFs list SID LAN FRA POS a.a. RBS sequence STA STO 100733 960RF001 1 25999..29142 1047 ccttgaatcgaaaggaggttagcct ttg taa 100734 96ORF002 1 32008. .33906 632 tttttacgactaaaggaggcaacca atg taa 100735 960RF003 1 30109..31995 628 ttatattttagataaggagtagcct atg taa 100736 960RF004 1 36760. .38634 624 attttgattgaaatgaggtgcatac atg taa 100737 960RF005 3 33903..35729 608 gtttattcgaaggaaaggtggttga ata taa 100738 960RF006 2 | 40589. .42043 484 aatgatttagggtaggtgttgacca atg | tag 100739 960RF007 1 18652..20091 479 tatacacacatactaaacctgaacg att tga 100740 96ORF008 2 8960. .10201 413 tggcagaatttgggggcgataacga atg tga 100741 960RF009 2 17447..18670 407 gacgcaataacggaagtgatcgtca atg tga 100742 960RF010 1 38647..39819 390 taaatataaataaagaggtgtgtaa atg tga 100743 960RF011 -1 119..1195 358 gtagctcgcctacccttattatttt ttg tga 100744 960RF012 2 20045..21013 322 tttaatgacaaattacctgacatag atg tga 100745 960RF013 3 29157..30098 313 acttattataagggaggtttgttag ttg taa 100746 96ORF014 1 21925..22839 304 agaaaataaagtgaggtaataaaat atg tag 100747 960RF015 1 5812..6591 259 atacacggtaaaggtgggagaatag atg taa 100748 960RF016 1 7852..8607 251 aataaaatgttgaaaggagagaaaa atg taa 100749 960RF017 3 3444..4190 248 aaatttaacattaatatcactttaa gtg taa 100750 960RF018 -3 28281..29000 239 taagctatgttgaacatcgctagtc atg tga 100751 960RF019 3 7188..7859 223 tttaccgttctaggacgtggtttaa atg taa 100752 960RF020 3 21324..21908 194 gaagggcaaaaaggagttttgatat atg taa 100753 960RF021 3 6612..7175 187 attaaaaattaattaaaaggacggt ata tag 100754 960RF022 2 24536..25093 185 aaagaaaaacgaaggagtgtattaa atg taa 100755 960RF023 1 5275..5811 178 catgaaatggtaggaggtatgaaaa gtg tag 100756 960RF024 3 14481..15014 177 taaaacgataggagataacgaataa atg taa 100757 960RF025 2 25157..25666 169 ataaaaaaattgaaaagaggtatat att taa 100758 960RF026 -3 15084..15590 168 tcattcttaacatagcccttaattc atg tga 100759 960RF027 -1 1229..1732 167 aatagcaaataaaggagtgtaaaac atg taa 100760 96ORF028 1 16960..17454 164 aaggcgtgtgatacagtgaaaacaa ttg taa 100761 960RF029 -1 1736..2227 163 tatgagaaaaggagtcatataaaag atg taa 100762 960RF030 1 25531..25995 154 ttttcaagagggagagtcgctcgta ctg tag 100763 960RF031 2 23633..24097 154 tttagtattgaaggtgattctgtag atc tag 100764 96ORF032 -2 2248. .2706 152 ataagacaccaaaggggtttggcgc atg tga 100765 960RF033 -3 39147..39605 152 agcatataaatcgtttagtgtttgt ttg taa 100766 960RF034 2 13181..13615 144 tagaagtcgaaaaagtggaggcaat ata taa 100767 960RF035 2 10628. .11053 141 gagctaggattgcaagcaacgatat ttg tga 100768 960RF036 2 24110. .24535 141 gtatttttcatagaggtggttaaat atg taa 100769 960RF037 1 12583..12996 137 atgaggaacagaagcaaccaacttt att tga 100770 960RF038 1 15628..16032 134 atgttaagaatgatgcctagtttaa ttg taa 100771 960RF039 3 39816..40220 134 ctaatacactttacttaattaaggg gtg taa 100772 960RF040 -3 27528..27932 134 tttccataaataaacgaggacacca atg tga 100773 96ORF041 3 16206..16607 133 gatgagggcggaggtgtcagagtag atg tga 100774 960RF042 2 35720..36106 128 aagttactataactaaaattatggg gtg taa 100775 96ORF043 -2 35713..36081 122 ttaaacgtccccctcagtatttgtt ttg taa 100776 960RF044 -2 9460..9828 122 agtatccatcagttgaagataatct ata taa 100777 960RF045 -3 5139..5504 121 ttctttttgtattctgtaatattca att tga 100778 960RF046 2 11513..11872 119 aagtaaatgtatagaggtggaataa atg taa 100779 960RF047 2 22991. .23350 119 gtcgtactacgtctgataagagcga gtg tag 100780 960RF048 3 8607..8963 118 tggaaaaagaattgagtgatgacta atg tga 100781 960RF049 1 23353..23697 114 atccgtttaaaccaataaggtagag gtg taa 100782 960RF050 -2 2728..3072 114 tggtaaattagtattacattaagta ata taa 100783 960RF051 3 4692..5021 109 tcaaaatatacggaggtagtcaact atg tga 100784 960RF052 -1 20882..21211 109 gtagcaaagagacaactaaaaaagt gtg taa 100785 960RF053 1 40252..40578 108 acgactaattttttagtcgtttttt att tag 100786 960RF054 1 4942..5262 106 aatataaaactaaaaaacaaaattt atg tag 100787 960RF055 -2 4840..5151 103 ccgtcgcaatatatagttcgcttaa atc taa, 100788 960RF056 3 36324..36623 99 aatttaacacaaagtaggtggcgta atg -taa 100789 960RF057 2 1394..1690 98 cttcagtggctcttttagcatttaa ata"' taa 100790 960RF058 -3 26247..26537 96 tacttcttttctcataatctgacca att tga 100791 96ORF059 -1 21485..21772 95 agactcaacgcctttttgaacatac ttg tga 100792 960RF060 -3 22647. .22931 94 cctctttgtaaccgacaagactgta ata taa 100793 960RF061 1 14023. .14304 93 ttatctaattaagggggacgagtga gtg taa 100794 96ORF062 -2 38281..38559 |92 tatataacttagcgattgtacttgc ttg taa WO 00/32825 PCT/IB99/02040 200 100795 960RF063 -3 30786..31064 92 gtctcctaatactacatcttgctta gtg tga 100796 96eRF064 -2 30205..30480 - 91 atgcatctacttttggatgtaatac ata tag 100797 960RF065 1 2617..2886 89 Iaaggtctaataaaaatttctccttc ttg taa 100798 960RF066 3 28056. .28325 89 aaggtgtagtcggctggttaactga att taa 100799 960RF067 -3 17142. .17411 89 ttccgttattgcgtcgtgaagttgt ttg tga 100800 960RF068 2 12326..12589 87 aatgcatgtcgtttggtctgcctaa ttg tag 100801 960RF069 2 42734. .42997 87 tttttaggcaacgatataagtaaaa gtg taa 100802 960RF070 1 11869..12129 86 aaatgttcaagaaatggagtgaagc ata taa 100803 960RF071 3 15396. .15656 86 aacaaqctatacaaattatcgataa att taa 100804 960RF072 -3 37749..38009 86 agattttttcgggttacccctagac att taa 100805 960RF073 3 11244. .11501 85 acatgcatatatagaggtggaataa atg tag 100806 960RF074 -3 42936..43193 85 aattatttaacttactaattttctt ttg taa 100807 960RF075 -3 26610..26867 85 tactgccaatgttccatcttcaacc att taa 100808 960RF076 -1 11126. .11380 84 tttatctaatacatttaagttaacc atc taa 100809 960RF077 -2 16537..16791 84 tacccaccatataggcaggtagtag gtg tag 100810 960RF078 -3 19521..19775 84 aataactttgaattgatacctcaac ata tga 100811 960RF079 3 13608..13859 83 ttagggcaaatggaggcagacacaa atg tag 100812 960RFOBO -3 28029..28280 83 tgagaagtcgccagtaagcaactga att tga 100813 960RF081 3 20973..21221 82 aatgaagttatcccattcatgactt atc tag 100814 960RF062 -1 8729..8974 81 cgattattgtgctttcaatttcaaa ttg tga 100815 960RF083 -3 3147..3392 81 tttagcctttatataatcaacttct gtg tga 100816 960RF084 3 1611..1853 80 tgctttatctttagtttctttcttt ttg tga 100817 960RF085 -2 29470..29709 79 ctcttatcaccttcgtttgtaggca atc taa 100818 960RF086 1 35188. 35424 78 gcgcaaggcgatttgggatatttaa Ctg tag 100819 960RF087 -2 13039. .13275 78 ttttgattgagctctaaagtgtctt att tag 100820 960RF088 3 24930. .25163 77 gaactatcattaaaagttaaatgga ata tga 100821 960RF089 -3 22329. .22562 77 tccagtataagatagtggtaatccc ata taa 100822 960RF090 -3 16803. .17036 77 acctttagtcgaataccctgcgtca ata tag 100823 960RF091 -1 22559..22789 76 aacgcttctggtttaacgttcatgt atg taa 100824 960RF092 3 18360..18587 75 attgcaaaagatattgtaagtagat atg taa 100825 960RF093 -2 25384. .25608 74 catgatttccttgtaattctctttc atc taa 100826 960RF094 1 10417..10638 73 aacacacattaaggagtgttaaaaa atg tag 100827 960RF095 3 12963. .13184 73 tactaaacgaagataaaactatgac att taa 100828 960RF096 1 42994. .43212 72 gatcgcttgaaaacgaagaagataa ata taa 100829 960RF097 -1 36047. .36265 72 tcaagcattacacctgtgacttttc atc taa 100830 960RF098 -2 36766..36984 72 caggttccggtacaaatccagatga ata taa 100831 960RF099 -2 34765..34983 72 tcattctttttataaaacgggtacc atg tag 100832 960RF100 1 10198..10413 71 acaagaagactcagaggtttttcac atg taa 100833 960RF101 1 15208..15423 71 gagaaacaagttaagataaggagag atg tga 100834 960RF102 3 4209..4424 71 attttaaaacgaaatataggagagg ctg tag 100835 960RF103 3 11673. .11888 71 catgcaccttatggtatgcgcttag ctg taa 100836 960RF104 3 12117..12332 71 tttacgtccaaagagcttttgactt gtg taa 100837 960RF105 3 23892..24107 71 gatggtgggttatccagtgttataa gtg taa 100838 960RF106 -3 34428. .34643 71 tagacttttgccaatttgttgttga att taa 100839 960RF107 -3 24495..24710 71 ggcacattaccaattgttaatttaa atg taa 100840 960RFI08 -1 23876. .24088 70 acatatttaaccacctctatgaaaa ata taa 100841 96ORF109 -2 17317. .17529 70 acctgtacgctttgctccgtgatta att taa 100842 96ORF110 -3 38931. .39143 70 actttcattcttttcgatgtaagaa atg taa 100843 960RF1ll -3 21855. .22067 70 agtaaattttttcttttgtgctgtc att tga 100844 960RF112 1 3217. .3426 69 aaatgtcaacgggaggtgatacgaa atg taa 100845 960RF113 -1 25469. .25678 69 tcagggatatatcctaaatatctag ctg taa 100846 960RF114 -2 9838. .10047 69 ataataatcatcacggtaaagtagc atc tga 100847 960RF115 1 13819. .14022 67 gcagtaggggttatggcaggtcaag ttg tga 100848 960RF116 -1 41033. .41236 67 caacttcatgacctgcatgtcttaa ata taa 100849 960RF117 -3 24711. .24914 67 tctgctgtattccatttaactttta atg Itaa 100850 960RF118 -1 12374. .12574 66 tccatctcctctaaaataaagttgg ttg taa 100851 960RF119 -1 3980. .4180 66 ctcctatatttcgttttaaaatttc att tga 100852 96OR~F120 -3 6033. .6233 66 ttgtaatttagaaatataacgataa ata taa 100853 960RF121 -2 37939. .38136 65 ctgaaatgccttgatacttgcctaa att tga 100854 960RF122 2 37892. .38 -086 64 acgacaaaaacaacaataagaatta gtg tga 100855 960RF123 -73 29193. .29387 64 ggacgtctgactttaaatgtgaagc ata tga 100856 960RF124 1 4408. .4599 63 tttatcggtaccaatttaatgatta atg taa 100857 96-RF125 -1 7787..7978 63 ttaaaaatccaagttttgccatcgt att tga 100858 RF126 -3 27027..27218 63 aaatttgaacaacggcattaattga gtg tga 100859 960RF127 3 15051. .15239 62 atcgagtcaaggaggttttggggaa gtg -- tga 100860 960RF128 - 1 6914. .7102 62 agcgaatgggtttgattgttgactc ata -- ~ 100861 960RF129 -3 31332..31520 62 tcttatttgctctgcttgtctataa atg tga 100862 RF130 -3 30084..30272 62 gaaatcatcttcaccttcaacatga gtg taa 100863 960RF131 13 11058. .11243 61 1 agaaaaagagaaatgaagtgatcta atg taa 100864 96RF132 -1 36434..36619 61 taagcatggtaatcacctcctttaa ata tga 100865 960RF133 -1 35591..35776 61 ctaaactattgcgtaaaccgccagt att taa 100866 -2 9250..9435 61 atccatgagcttataacccgtcta att tga WO 00/32825 PCT/IB99/02040 201 100867 960RF135 1 29563..29745 60 cgacaactttttgtaggactagtaa gtg tga 100868 960RF136 -3 12486..12668 60 cactttactttcaacttgttcagga ttg taa 100869 960RF137 -1 14501..14680 59 caaactgaaagctaagtaatcagca atc tga 100810 960RF138 -2 23326. .23505 59 cttgtgacatttgatgaaattttag ttg tga 100871 960RF139 -3 42672. .42851 59 aatccggaatttttagcaattttat atc taa 100872 960RF140 -3 31137..31316 59 acttgattgactagtaaagtcgtac atg taa 100873 960RF141 -3 18969..19148 59 aacaaaaataacattatagggatct ata taa 100874 96ORF142 -3 4740..4919 59 cataaattttgttttttagttttat att tga 100875 960RF143 2 36107..36283 58 aacaaatactgagggggacgtttaa atg taa 100876 960RF144 3 16029. .16205 58 tatacgaagtaaagaaggtagataa ata tag 100877 960RF145 -3 29013..29189 58 tgtcactgacgcgatactgtgaacc att tga 100878 960RF146- -3 14883. .15059 58 aatctttgaatgttgtgactaagta ttg taa 100879 960RF147 -1 .18251. .18424 57 tatcagcgttaattgcacgtaatct atg taa 100880 960RF148 -1 13583. .13756 57 aataccttctttaactgaatgttga ata taa 100881 960RF149 -2 10756. .10929 57 taaattcacatctctatactgatat_ ctg tag 100882 960RF150 2 14171. .14341 56 atttttaatgaagaagtgttattaa ctg tag 100883 960RF151 2 19217. .19387 56 cctacatactcattgcgctactttt atg tga 100884 960RF152 -1 12614. .12784 56 atttctacagtaaaaatatctttat ctg taa 100885 960RF153 -2 11836. .12006 56 ttgcattacctattgcgaatgctag ttg taa 100886 960RF154 -2 4165. .4335 56 atataacgcttttgtcctcgaccaa atc tga 100887 960RF155 -3 40464. .40634 56 aaatcaggattgaactgcttcccta atg tga 100888 960RF156 3 423. .590 55 tggtaattttgataatttagcttta ata taa 100889 960RF157 -1 41879. .42046 55 gtagcaaaatttttattctaagtaa ata taa 100890 960RF158 -2 36166. .36333_ 55 cattcatgttcgtgccgtttggtaa atc tag 100891 960RF159 -2 16228. .16395 55 tttaacatctgagcataccttttat ttg taa 100892 960RF160 3 1038. .1202 5-4 atctctaagcagttgttgagcagcg ttg taa 100893 960RF161 -1 19193. .19357 54 tctttgttgttaggtacaccaaaca atg tag 100894 960RF162 -1 18074. .18238 54 ctcgtcctattaacacaatagatcc ata -tga 100895 960RF163 -1 15386. .15550 54 agccatcataggactgtaaaattca ctg taa 100896 960RF164 -1 10049. .10213 54 tacatcgatttcaataagcttttga att tag 100897 960RF165 -2 18514. .18678 54 gtgcttcaatatcatctattaactt ata taa 100898 960RF166 -2 11104. .11268 54 ctagccatgattacccttaaattag ttg tag 100899 960RF167 -3 13764. .13928 54 agacagtttataatgtgtatctcta ata tga 100900 960RF168 1 14305. .14466 53 ttttgaatttttggaggacgagtaa atg tag 100901 .960RF169 -1 17885. .18046 53 gtgttgaagccttaatagactcttt ata tga 100902 960RF170 -1 10790. .10951 53 taggcgctttacatatccacgttaa att taa 100903 960RF171 -3 12765. .12926 53 atcttcgtttagtatataaaacgct ctg taa 100904 960RF172 3 22836. .22994 52 cgttcgcaacgcttaaaccaactga ata tga. 100905 960RF173 -1 15956. .16114 52 ctctacatcatcattagccgtcgtc ata taa 100906 960RF174 -1 10571. .10729 52 tagtgccattcatattactttctaa ata Itaa 100907 96ORF175 -1 j3440. .3598 52 cagcctatcttcactatcaacatga ttg taa 100908 960RF176 -3 37170. .37328 52 tttatctaaaacattgctgtaagca gtg taa 100909 960RF177 -3 6693. .6851 52 ttcctaatctactaagtaactcgat ata taa 100910 960RF178 -3 5655. .5813 52 gacatcttgattagttttttcagtc atc tag 100911 960RF179 1 34564. .34719 51 gttacagctgaagtcgataaaatag ttg tag 100912 960RF180 1 42661. .42816 51 atataaattctaacactaaaatact atg tga 100913 960RF181 -2 37741. .37896 51 tggacgcactgtcaactgatgtttt atc taa 100914 960RF182 -2 25039. .25194 51 ttcgtaatctttttctccgtcaeta att tga 100915 960RF183 -2 4534. .4689 5 tcagttttaatattttcagccatag ttg tga 100916 96ORP~184- 1 6721. .6873 50 ggagctggagaatttacagtaaaag ttg tag 100917 960RF185 2 36548. .36700 50 acaaaaatatacgcgatatgaaaat gtg taa 100918 960RF186 -1 40025. .40177 s0 tggagatcctgaataaacatcactt ata tga 100919 960RF187 -1 34466. .34618 50 attacctttaacaaggtcagcgcca ttg tga 100920 960RF188 -1 33842. .33994 50 agttcctctatctgattcatagaaa ctg taa 100921 960RF189 -1 24914. .25066 50 acatagaatggtcttccgtgtgtga ate taa 100922 960RF190 -- 2 20395. .20547 50 tatcttagagtaaccctctccactc ata tga 100923 960RF191 3 24768. .24917 49 aaaggaattgaagcagtgaaacacg ctg taa 100924 960RF192 -1 16169. .16318 49 ttgtggtttcggcaacgttgcttgt atg tga 100925 960RF193 -2 39100. .39249 49 cagtaccgtttttaccgggtgcgcc ttg t aa 100926 96RF194 -2 25921. .26070 49 ttggtacagacgtctttgctaatcg ttg taa 100927 960RF195 -2 17779. .17928 49 caaccaatgctcgggatggtcaggg ttg tga 100928 96ORF196 -2 14182. .14331 49 1ttaaatacttttcttctagcaatgc ate tga 100929 960RF197 -2 7609. .7758 49 ttatcatcaaacgacttaacaccaa ttg tga 100930 960RF198 -2 1537. .1686 49 ttattagctagtgcgttagtgttag gtg taa 100931 960RF199 -3 7719. .7868 -49 taatacttgtatcggatagtcatct att -- taa 100O932 960RF200 2 22271. .22417 48 ttctttaatgaggttaaacctctaa ttg -t a§ 100933 960RF201 2 30353. .30499 48 tctactattggcgaaaaaaeaaggc t tg tag 100934 960RF202 2 1 32591. .32737 48 agattgaagcccaacggacaattta ttg taa 100935 960RF203 2 39131. .39277 48 [agcaaagactttaaagagaaaatag ata tag 100936 960RF204 -2 36985. .37131_ 48 atcttcctggagaacctgtccaact att tga 100937 96RF205 -3 38721..38867 48 aaggaaccattttacaacatcgtcg ata taa 100938 960RF206 -3 35880. .36026 48 gttaacatagcgetetgttgcgtc att taa WO 00/32825 PCT/IB99/02040 202 100939 960RF207 -3 11550..11696 48 ttgctctctcgctccatgattttgg ata taa 100940 960RF208 2 37178..37321 47 agattagtaagacacccttatgtaa gtg taa 100941 96ORF209 2 42341..42484 47 tgcatatttaaaccacccatactag ttg taa 100942 960RF210 3 41850..41993 47 aaaggtaataacgtaagggacggct att tag 100943 96ORF211 -1 6662..6805 47 ttgttggaatggtgggacgaattgg ttg tga 100944 960RF212 -2 25213..25356 47 agtagcacattcccaaaattgtaaa atc taa 100945 960RF213 -3 42219..42362 47 gtggtttgatcatttataatataac ata taa 100946 960RF214 3 27834..27974 46 aaaagattttagacttcgttagaac atc tag 100947 960RF215 3 35811..35951 46 ttacgcaatagtttagatgtagacg ata taa 100948 960RF216 -1 5402..5542 46 tttccgtaaggtgtattcaacttga att tga 100949 960RF217 -2 24229..24369 46 tataggtctgttaagcacataacct atc taa 100950 960RF218 -2 6253..6393 46 ttgtcattcttgctaacacgtcaga ttg taa 100951 960RF219 1 883..1020 45 aaatcactcccgaaatattcgttaa ata taa 100952 960RF220 2 32936..33073 45 gataaaggtatagacaaagtattgt atc taa 100953 960RF221 3 41703..41840 45 ggtaagcctataggtggtttggtag ctg taa 100954 960RF222 -1 39860. .39997 45 acttttattaggttcaactccattt att taa 100955 960RF223 -1 24716..24853 45 acatttcaaatgattctggaacaac ata taa 100956 960RF224 -2 26794..26931 45 caatatcacgccatgtagtttttaa ctg taa 100957 960RF225 -2 19201..19338 45 caaacaatggattgtaatcaaataa atg tga 100958 960RF226 -2 15709..15846 45 tgacttgcttgttgtctaacacaat ata taa 100959 960RF227 -3 36711..36848 45 acattgactgccccgataattatct ata tga 100960 96ORF228 3 2325..2459 44 tcgccatagtgagttccaataccgt ata taa 100961 960RF229 -1 38612..38746 44 ttgtcattgatacctattcttatag atg tga 100962 960RF230 -1 31733..31867 44 gctggattgtatggcttaaagtaat ctg tag 100963 960RF231 -2 12076..12210 44 tgactcatagctttaacttgttcgt ctg taa 100964 960RF232 -3 31644..31778 44 atagtcctcaagtgttaaccctagt ttg taa 100965 960RF233 -3 23988..24122 44 atttgatttgtaagttcaggctcaa ctg taa 100966 960RF234 -3 17529..17663 44 agtacgtttttttgaatcgtaccta atg taa 100967 960RF235 1 7153..7284 43 aatgctaatggtccaatagaaatca atg tag 100968 960RF236 2 2681..2812 43 ttctttcacttcaacttcacatttc ata tga 100969 960RF237 2 4496..4627 43 gtactatgcttcacagtcttagcga ttg taa 100970 960RF238 -1 41720..41851 43 cacctgtaattcttgaattagttga ata tga 100971 96ORF239 -1 35324..35455 43 acttactaataaaatagaatagttt gtg taa 100972 960RF240 -1 8570..8701 43 atccccgttttgacttaatacatca atc tga 100973 960RF241 -2 33502..33633 43 ataattttgtaatactcttagggat atg tag 100974 960RF242 -2 23662..23793 43 agctaatgctacagcagtgttgtaa atc tag 100975 960RF243 -3 32391..32522 43 acctggacgagcttgcgtcatataa ata tag 100976 960RF244 -3 30273..30404 43 aaaactttcgttatactcttggtaa atc tga 100977 960RF245 -3 5895..6026 43 tgcactaaaatgcttataattctta atc taa 100978 960RF246 -3 2679..2810 43 attcatcaagaaactatagccggtc atg tga 100979 960RF247 1 34891..35019 42 acatcaagcaaatctggtgtgttag ttg taa 100980 960RF248 2 30668. .30796 42 aattattacattaaagctggtgtga atg tag 100981 960RF249 2 31838..31966 42 caaatattagcttgtagtgagttag atg taa 100982 96ORF250 2 33539. .33667 42 cttaccagaaacagcacaggtagaa ata taa 100983 96ORF251 -1 20486..20614 42 cttctgtacgagccacacgcaatga ttg tag 100984 96ORF252 -1 15128. .15256 42 gatatetcattactagctactacta ata tga 100985 960RF253 -2 41446. .41574 42 aaaacctaattcagataaacgataa ttg tga 100986 960RF254 -2 41005..41133 42 gttataaccatgaccggctacaagc ata taa 100987 960RF255 -2 23008..23136 42 aggataaatgacttgaccatctttc ata taa 100988 960RF256 -2 14794..14922 42 ttgtatgcgtcaatgagttggtcga ttg tag 100989 960RF257 -2 8503..8631 42 tacctaacttttttaataatttcta atg tga 100990 960RF258 -3 22143. .22271 42 aaacgctttgtaaaatgcctctgca att tga 100991 960RF259 -3 18639..18767 42 cttgtatctattatagagattaacc att tag 100992 960RF260 -3 15624..15752 42 gttttggtaactagccactgtatag ata taa 100993 960RF261 2 18746..18871 41 catattgaggctctaatagagtcac ata taa 100994 960RF262 -1 13067..13192 41 aattaattaattcttctcttgttgg ttg taa 100995 960RF263 -2 18742..18867 41 taacagacacgtctaatcgccttac att tga 100996 960RF264 -2 18376..18501 41 catattatcataaagaacaagtaac ttg taa 100997 960RF265 -2 367..492 41 ctaaacgaaaaagagggtacaatac atc tga 100998 960RF266 -3 32802..32927 41 aggtatatccatttgatacaatact ttg taa 100999 960RF267 -3 10194..10319 41 atcatcgaaaggcgataactcgtta ttg tga 101000 960RF268 1 1159..1281 40 ttattcttcctttttgtaattgtaa atg taa 101001 960RF269 2 10373..10495 40 gacagagttgaaaagaaaatcatga atg taa 101002 960RF270 2 15734..15856 40 ttattcggcgtaatcgcactgatgc ttg tag 101003 960RF271 -1 43451..43573 40 c c tNo shine-dalgarno att -- tg sequence 101004 960RF272 -1 36959..37081 40 acgctataaaaataacttttattag at# tag 101005 960RF273 -1 35798..35920 40 ctgacgcactttgttggtttgatgc att taa 101006 960RF274 -1 8147..8269 40 1 tctgtectctctatgtttgttagtct ctg tga 101007 96ORF275 -2 43066..43188 40 tttaacttactaattttcttttgat ata tga 101008 960RF276 -2 42535..42657 40 aaataatgtaaattgttttcatagt att tag 101009 960RF277 -2 30628..30750 40 tttgtagtcccgcttctgcaaaagt ctg ta WO 00/32825 PCT/IB99/02040 203 101010 960RF278 -2 13291..13413 40 ttcgtatettccaagcaatteattt ttg tga 101011 96ORF'279 -2 3172. .3294 40 cagattgtttagtaacgcctaattt atc taa 101012 960RF280 -3 18804..18926 40 taaataaccaacacgtgtatcaaca att tag 101013 960RF281 -3 15843..15965 40 atttaaaaagtgtattctataacca ate tag 101014 960RF282 -3 8460..8582 40 ttagtcatcactcaattctttttcc att taa 101015 960RF283 -3 7593..7715 40 gatgttgtctacacagtgctaacac atg taa 101016 960RF284 -3 6453.:.6575 40 aattaatttttaattaccatttcta att tga 101017 96ORF285 1 15082. .15201 39 eaataeetagteacaacattcaaag att taa 101018 960RF286 1 34444..34563 39 acacaaacgttaatagcaaaagtga atg tag 101019 960RF287 2 27920..28039 39 eetattttagcagttgtcagtaa ttg tag 101020 960RF288 2 28415..28534 39 atcggctttttaaetggegtaatga ate tag 101021 960RF289 2 38147..38266 39 tatcaaatgettaatttaggcaagt ate tga 101022 960RF290 3 40917..41036 39 gcaaatttaaacactttcacatcat atg taa 101023 960RF291 -2 38815. .38934 39 tctetaaaaacagettaeagcgaac Iata taa 101024 960RF292 -- 2 32671. .32790 39 ctataggattataaatcgetgacgt ata tga 101025 960RF293 -2 31216. .31335 39 ttgatttgatgtttcttatacttga ttg taa 101026 960RF294 -2 21589. .21708 39 gtatcttcatcagaatcgcctaaaa ate taa 101027 960RF295 -2 18976. .19095 39 tatcaatatatgctaacctagcaec ata taa 101028 960RF296 -2 11482. .11601 39 1gccacctcgtaetctttttgcaaec att taa 101029 960RF297 -3 12933. .13052 39 teacgaaataatgtttetttaattt ata taa 101030 960RF298 -3 8262. .8381 39 gaactgatcttgcttaaatgattta att_ tag 101031 960RF299 -3 6993. .7112 39 eattageattagcgaatgggtttga ttg tga 101032 960RF300 2 23516. .23632 38 aetacatctgaacaactaaaatote ate tag 101033 960RF301 2 125943. .26059 38 agattagaagaagaaaaaagaagac gtg taa 101034 960RF302 2 36929. .37045 38 tattggggttttgtaacatggggca atg tag 101035 960RF303 3 4476. .4592 38 ataaaagctacetagtagcagtact atg tga 101036 960RF304 3 20586. .20702 38 tactctaagatagctaaagcaatac gtg Itga 101037 960RF305 3 28356. .28472 38 cggttaccaatgtgcttgatacgat ttg taa 101038 960RF306 -1 24359. .24475 38 acttaaataaaagccgtatcgtgcc atg taa 101039 960RF307 -1 20147. .20263 38 ttgtacctatacgagttaactcctt att tag 101040 960RF308 -2 138158. .38274 38 1ttecgtatccactttctaagaaagc gtg tga 101041 960RF309 -2 35149. .35265 38 agcttgtttgtatcgtctttaacga ata taa 101042 96ORF310 -2 31423. .31539 38 gtaatatgattaggtctcctcttat ttg taa 101043 960RF311 -2 10438. .10554 38 egcetttaaatcgttttaggteact atc taa 101044 960RF312 -2 1390. .1506 38 gagaacaacaeaaacattaaeaaca ate taa 101045 960RF313 -3 33051.-33167 38 acgtcetgtttctagatcgtaatac ata tag 101046 960RF314 -3 25194. .25310 38 agcaaaccgttaaagataacattga ate taa 101047 960RF315 -3 6273. .6389 38 eattettgetaaeaegtcagattga etg tga 101048 960RF316 -3 4281. .4397 38 ataattcgtattcattaatcattaa att tag 101049 960RF317 1 2260. .2373 37 atgaetccttttcteatatttcttt ata taa 101050 96ORF318 2 21230. .21343 37 atttcacacttttttagttgtctct ttg taa 101051 960RF319 3 18018. .18131 37 ataetgagtcaecaatttaageecg atg tag 101052 960RF320 3 36972. .37085 37 attacagatatcctaagggtttccg att taa 101053 960RF321 -1 36302. .36415 37 etcttgagttttttgacctaattta ate taa 101054 960RF322 -1 32606. .32719 37 eeataagttattteteeagttetat att- taa 101055 960RF323 -1 11453. .11566 37 ttaaaeegttettttttateaatc att tga 101056 960RF324 -1 7268. .7381 37 taetggetegeeeeagtgaagttet ata tga 101057 96ORF325 -2 32347. .32460 37 ttaetgeatttgtatatggegataa ate tag 101058 960RF326 -2 24682. .24795 37 aegtttattaegeteataaageeat ata tag 101059 960RF327 -2 23905. .24018 37 1aaatggetgtggegettgaeeatat gtg taa 101060 960RF328 -2 21460. .21573 37 agagataataegtttttgttett etg tga 101061 960RF329 -2 21208. .21321 37 gaettaaettettegatattcatat ate tga 101062 O6RF330 -2 18085. .18198 37 eeagtegaeaeeageaaagtattet ttg tag 101063 960RF331 -2 8170. .8283 37 aetttgagaegtegtetgtetetet atg tag 101064 960RF332 -2 5971. .6084 37 eaatttgtttteegttttetcttag ttg Itag 101065 96ORF333 -3 37632. .37745 37 aeettgettaateaagtegtaatta att tga 101066 960RF334 -3 29628. .29741 37 etgagttagtgttgtaaaatgteat ttg tag 101067 960RF335 -3 7164. .7277 37 ttageggatateegttttetagtaa ate taa 101068 960RF336 1 22903. .23013 36 gtaaaaaaagaeaatatgaeeatta etg tga 101069 960RF337 1 43258. .43368 36 taattgaegtggttattttttaggt ttg taa 101070 960RF338 2 112668. .12778 36 gaaetggtggaatgggeatggaaea ate tag 101071 960RF339 2 128292. .28402 36 tteaeegetttaatteagttgetta etg taa 101072 96ORF340 2 35396. .35506 36 tteetaatgaaeataagteaaeggt att tga 101073 960RF341 3 25428. .25538 36 aetegagaaeaattagaaaaageaa ttg tga 101074 960RF342 -1 40913. .41023 36 tateegggaaatttaatetaataaa ata-- tga 101075 960RF343 -1 39173. .39283 36 tgeeaeattttagtgteaggattga ttg -. t 101076 960RF344 -1 37580. .37690 36 gggteeaeetttaaegtegttteag a ta taa 101077 96ORF345 -1 31556. .31666 36 ggattatetttetaataaetteaa ttg tga 101078 96RF346 -1 29972. 30082 3 6 ggetaeoeettatetaaaatataat ttg taa 101079 960RF347 -1 28787. .28897 36 c tgeeaaagtetgtageaattaett ttg tga 101080 9-60RF348 -1 21839. .21949 36 F taa~aateegataaaataaeattge etg tga 101081 96RF34.9 -1 I3647. .3757 36 1taaaettegaagttaeeeagege ttg tga WO 00/32825 PCT/IB99/02040 204 101082 960RF350 -2 -40801..40911 36 accattccaattttgceeatatgat gtg tag 101083 960RF351 -2 38953..39063 36 tatcttttaaaattCtcgtaatage atc taa 101084 960RF352 -2 31585..31695 36 tagctgtcatcactagtatttttga ate taa 101085 960RF353 -2 24550..24660 36 atagtccgttttacegcctcgtaet att tag 101086 960RF354 -2 20083..20193 36 ateatcattttgatatttcteaaae ata tga 101087 960RF355 -2 991. .1101 36 gcatcttggeagtacgacgtaaaac ate tag 101088 960RF356 -3 38148..38258 36 taagaaagegtgcgegatcaaataa att tga 101089 960RF357 -3 8790..8900 36 tgaagttatctagcgctatttttet ttg tag 101090 960RF358 -3 4458. .4568 36 tteataaaagtattctttgtagtat atg tag 101091 960RF359 1 4666..4773 35 ttateaaaatatacaacttaattaa atc tag 101092 960RF360 1 11569. .11676 35 ataaatttaeegaacatgaaaatga att tga 101093 960RF361 2 6122..6229 35 ggaaaacaaattgatgttgtagtga ttg taa 101094 960RF362 -1 40418..40525 35 ttcgtaggtgtcattacttctttaa ttg ta 101095 960RF363 -1 34358..34465 35 gttttgettgatttcgatttgttga atg tga 101096 960RF364 -1 20654..20761 35 ctatttccactgatteceatctaa atg tga 101097 960RF365 -1 8423..8530 35 tcttttttagagttacgaggtttca att tag 101098 960RF366 -1 2402..2509 35 tgacgtatggeaaeattttagatca atc taa 101099 960RF367 -2 36607..36714 35 aaaataaaaagecagtgeegaagca ctg tag 101100 960RF368 -2 27061. .27168 35 caaatcgtcctgeagcgttcaataa ate tag 101101 960RF369 -2 26470..26577 35 1atgagttgttaagtttacceaaat ate taa 101102 960RF370 -2 10327..10434 35 eegtgeeatetteteggtataagta ata taa 101103 960RF371 -2 8650..8757 35 gggtaegggttgttaetgttgatat atc taa 101104 960RF372 -3 14382..14489 35 gttttttaattgatetaetgttaa att taa 101105 960RF373 -3 8151..8258 35 atgtttgttagtetetgtgtagtet atg taa 101106 960RF374 -3 5007..5114 35 aaaegatttaagtggaaeattatte ata taa 101107 960RF375 2 30563..30667 34 egattagaaatetttaaaaaaggae ttg tga 101108 960RF376 -1 19916..20020 34 tetatgteaggtaatttgteattaa att taa 101109 960RF377 -1 9236..9340 34 ettttetgttagtaattgtttttaa ate taa 101110 96ORF378 -1 9026. .9130 34 aetetttateteagttgettttaa ata tag 101111 960RF379 -2 28447. .28551 34 ettttgtgataataaagtttagtgc ttg tga 101112 960RF380 -3 40329..40433 34 eeatttaeettettgagatgttgga ttg tga 101113 960RF381 -3 39801. .39905 34 eaaaagatgaaggettttteeatae ttg taa 101114 960RF382 -3 33831..33935 34 atgttgtttgtaaetegattaagtt ate tga 101115 960RF383 -3 33687..33791 34 gttattacgtettaataettgtgtt gtg tag 101116 960RF384 -3 13530. .13634 34 tataegeaetagtactgateaetga ttg taa 101117 960RF385 -3 3843..3947 34 tttgattgattgttctagttaagaa att taa 101118 960RF386 1 12256..12357 33 agteataaagaagttagcaatgtga ttg tag 101119 960RF387 2 2207. .2308 33 teeaagaetetttaaetgttaactt ate tag 101120 96ORF388 a 2 2519..2620 33 attgttgaatttegattgatetaaa atg tga 101121 960RF389 2 22517..22618 33 agaagtaaaatgegtaatgetttag atg tag 101122 960RF390 2 27302. .27403 33 tteeaaaattgggetaatagtgtag ctg taa 101123 960RF391 2 32384..32485 33 aetaaaaaggttgagaaagetgtag atg taa 101124 960RF392 2 39287..39388 33 aaaaaeggtaetgtagtateaatea atc tag 101125 960RF393 3 18153. .18254 33 gtagtatatgeegaetttgatttga atg taa 101126 960RF394 3 24189..24290 33 teagaeeetaaeattaaeaaaeeag ttg tga 101127 960RF395 -1 15266. .15367 33 tegataatttgtatagettgtttta atg tag 101128 960RF396 -2 32239. .32340 33 ttttagtgaaageatetagtgttga ata tag 101129 960RF397 -2 16123..16224 33 ttatgtgtgeetateatattaaeaa ttg tag 101130 960RF398 -2 13648. .13749 33 tetttaaetgaatgttgaatageat ttg tag 101131 960RF399 -2 10987. .11088 33 aettetgtaggtattcttatateaa ttg tga 101132 960RF400 -2 3382..3483 33 ettaeeggtaattctteaaaattaa atg taa 101133 960RF401 -3 40794..40895 33 eeatatgatgtgaaagtgtttaaat ttg taa 101134 960RF402 -3 39978..40079 33 atatteetaaateaettgaacaa att tga 101135 960RF403 -3 38607..38708 33 atetteagtgtaaaategaeageea atg tag 101136 960RF404 -3 21288..21389 33 eagaeaeegtettaagteeetttag ata taa WO 00/32825 PCT/IB99/02040 205 Table 11 SEQUENCE INFORMATION FOR PHAGES MATCHING WITH TABLE 1 M32695 Bacteriophage PM2 nuclease cleavage site gill66l45|gblM32695|BM2NCS [166145] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M32693 Bacteriophage PM2 Hind III fragment 4 gil166l44gbM32693|BM24HIND3 (166144] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M32693 Bacteriophage PM2 Hind III fragment 4 gi[166144|gblM32693|BM24HIND3 [166144] (View GenBank report,FASTA report,ASN.1 reportGraphical view, 1 MEDLINE link, or 1 nucleotide neighbor) M32694 Bacteriophage PM2 Hind III fragment 3 gill66l43jgbjM32694jBM23HIND3 [166143] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 1 MEDLINE link) M26134 Bacteriophage PM2 structural protein gene containing purine/pyrimidine rich regions and anti-Z-DNA-IgG binding regions, complete cds giI289360|gbjM26134|BM2PROTIV [289360] (View GenBank report,FASTA report,ASN.1 report,Graphical view, 1 MEDLINE link, or 1 protein link) J02452 bacteriophage fi 3-terminal region ma gil215409|gbIJ024521PFITR3 (215409] (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 1 MEDLINE link) AF020798 Bacteriophage Chp 1 genome DNA, complete sequence gi!2l776I|dbjjD00624|BCPl (217761] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 12 protein links, or 1 genome link) X72793 Clostridium botulinum C phage BONT/Ci, ANTP-139, ANTP-33, ANTP-17, ANTP-70 genes and ORF-22 gil51617 IembIX72793ICBCBONT (516171] (View GenBank report,FASTA reportASN. 1 reportGraphical view, I MEDLINE link, 6 protein links, or 4 nucleotide neighbors) X51464 Clostridium botulinum D Phage C3 gene for exoenzyme C3 giJ 149071emblX51464ICBDPE3 [14907] (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, I protein link, or 2 nucleotide neighbors) D90210 Bacteriophage c-st (from C. botulinum) CI-tox gene for botulinum Cl neurotoxin giJ217780ldbjjD902101CSTC ITOX (217780] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 1 protein link) 1 WO 00/32825 PCT/IB99/02040 206 S49407 type D neurotoxin [bacteriophage d-16 phi, host = C. botulinum, type D, CB16, Genomic, 4087 nt] gil260238igbjS49407IS49407 (260238] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 1 protein link) X53370 Bacteriophage phi29 temperature sensitive mutant TS2(98) DNA polymerase gene gil15733lembIX533701POTS298 [15733] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,! MEDLINE link, 1 protein link, or 7 nucleotide neighbors ) X53371 Bacteriophage phi29 temperature sensitive mutant TS2(24) DNA polymerase gene gil1573 llemblX5337IjPOTS224 (15731] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,1 MEDLINE link, I protein link, or 7 nucleotide neighbors ) X05973 Bacteriophage phi29 prohead RNA gil15680embIX059731POP29PRO [15680] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, or 4 nucleotide neighbors) VOI155 Left end of bacteriophage phi-29 coding for 15 potential proteins Among these are the terminal protein and the proteins encoded by the genes 1, 2 (sus), 3, and (probably) 4 gil15659|embVO1155|POP29B (15659] (View GenBank reportFASTA reportASN.I report,Graphical view,l MEDLINE link, 16 protein links, or 16 nucleotide neighbors) X73097 Bacteriophage phi-29 left origin of replication giJ312194embIX73097|BP29ORIL [312194] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 5 nucleotide neighbors) M14430 Bacteriophage phi-29 gene- 17 gene, complete cds gij21532ljgblM14430jP29GI7A [215321] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 6 protein links, or 8 nucleotide neighbors) M14431 Bacteriophage phi-29 gene-16 gene, complete cds gil2153191gbIM14431|P29GI6A (215319] (View GenBank reportFASTA reportASN.1 report,Graphical view,! MEDLINE link, 2 protein links, or 7 nucleotide neighbors) M20693 Bacteriophage phi-29 DNA, 3' end gil215343|gblM20693|P29REPINB (215343] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 4 nucleotide neighbors) M21016 Bacteriophage phi-29. DNA, 5' end gil215342|gb|M21016IP29REPINA [215342] (View GenBank reportFASTA reportASN.1 reportGraphical view,! MEDLINE link, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 -207 M12456 Bacteriophage phi-29 genes 9, 10 and 11 encoding p9 tail, incomplete, p10 connector, complete, and p1 1 lower collar, incomplete, respectively gil2l5338jgblMl2456|P29P9 [215338] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 .MEDLINE link, 3 protein links, or 2 nucleotide neighbors) M14782 Bacillus phage phi-29 head morphogenesis, major head protein. head fiber protein, tail protein, upper collar protein, lower collar protein, pre-neck appendage protein, morphogenesis(13), lysis, morphogenesis(15), encapsidation genes, complete cds gil2153231gb|M14782P29LATE2 [215323] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 11 protein links, or I 1 nucleotide neighbors) M26968 Bacteriophage phi-29 (from Bacillus subtilis) proteins p 1 delta-1 genes, complete cds, and the sus1(629) mutation gi1341558|gb1M26968|P29P1D1A [341558] (View GenBank reportFASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) J02448 Bacteriophage fl, complete genome gil 166201 lgbIJ024481F1CCG [166201] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 10 protein links, 205 nucleotide neighbors. or 1 genome link ) M24832 Bacteriophage f2 coat protein gene, partial cds gill66228|gbIM24832IF2CRNACA [166228] (View GenBank reportFASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors) J02451 Bacteriophage fd, strain 478, complete genome gil215394gb1J0245 I PFDCG [215394] (View GenBank report,FASTA report,ASN.1 reportGraphical view,5 MEDLINE links, 10 protein links, 204 nucleotide neighbors, or I genome link) M34834 Bacteriophage fr replicase gene, 5' end gill661391gblM348341BFRREGRA [166139] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 protein link, or 9 nucleotide neighbors) M38325 Bacteriophage fr replicase gene, 5' end gil166137|gbIM383251BFRREGR [166137] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 protein link, or 9 nucleotide neighbors) M35063 Bacteriophage fr coat protein replicase cistron (R region) RNA gil1661341gbIM350631BFRRCRRA [166134] (View GenBank report,FASTA report,ASN. I report,Graphical view, 1 protein link, or 3 nucleotide neighbors) S66567 alpha-atrial natriuretic factor/coat protein-fusion polypeptide [human, bacteriophage fr, expression vector pFAN15, PlasmidSyntheticRecombinant, 510 nt] gil435742|gbIS66567IS66567 [435742] (View GenBank report,FASTA report.ASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 15 nucleotide neighbors WO 00/32825 PCT/IB99/02040 208 X15031 Bacteriophage fr RNA genome gilI5071lembIX15031ILEBFRX [15071] (View GenBank report,FASTA report,ASN.1 report,Graphical view,l MEDLNE link, 4 protein links, 9 nucleotide neighbors, or 1 genome link) U51233 Mus musculus neutralizing anti-RNA-bacteriophage ft immunoglobulin variable region light chain (IgM) mRNA, partial cds gi11277150igbIU512331MMU51233 [1277150] (View GenBank report,FASTA report,ASN.1 report,Granhical view,l protein link, or 1669 nucleotide neighbors) US1232 Mus musculus neutralizing anti-RNA-bacteriophage fr immunoglobulin variable region heavy chain (IgM) mRNA, partial cds gil 12771481gblU512321MMU5 1232 [1277148] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I protein link, or 1073 nucleotide neighbors) U02303 Bacteriophage Ifl, complete genome gif3676280gbiU023031B2U02303 [3676280] (View GeriBank report,FASTA report,ASN.1 report,Graphical view,10 protein links, or I genome link) V00604 Phage M13 genome gij14959jembjV00604jRNM13X [14959] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, 10 protein links, or 205 nucleotide neighbors) A32252 Synthetic bacteriophage M13 protein III probe gil1567340|embIA32252|A32252 [1567340] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) A32251 Synthetic bacteriophage M13 protein III probe gil1567339|emblA32251|A32251 [1567339] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) M12465 Bacteriophage M13 mp10 mutations in lac operon gil2152l0|gblM12465jM13LACMUT [215210] (View GenBank reportFASTA reportASN.1 reportGraphical view,1 MIEDLINE link, or 215 nucleotide neighbors) M24177 Synthetic Bacteriophage M13 (clone M13.SV.B12) SV40 early promoter region DNA gil2094161gbIM24177|SYNSVB12 [209416] (View GenBank reportFASTA report,ASN. 1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M24176 Synthetic Bacteriophage M13 (clone M13.SV.B1 1) SV40 early promoter region DNA gil209415|gbIM241761SYNSVB 11 [209415] (View GenBank report.FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 -209 M24175 Synthetic Bacteriophage M13 (clone M13.SV.8) SV40 early promoter region DNA gil208806jgbjM24l75jSYNMl3SV8 [208806] (View Gen.Bank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, or 242 nucleotide neighbors) M19979 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gil207813gbIM199791SYN33M13M [207813] (View GenBank report,FASTA report,ASN.I report,Graphical view,l MEDLINE link, or 617 nucleotide neighbors) M19565 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gij207808jgbjM l 9565|SYN33M13H [207808] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 567 nucleotide neighbors) M19564 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gil207807jgbjMl9564jSYN33Ml3G [207807] (View GenBank report,FASTA reportASN.I report,Graphical view,l MEDLINE link, or 12 nucleotide neighbors) M19563 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gil2078061gbIM195631SYN33M13F [207806] (View GenBank report,FASTA report,ASN.I report,Graphical view,1 MEDLINE link, or 262 nucleotide neighbors) M19561 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 giI207804jgbjM1956ljSYN33M13D [207804] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 27 nucleotide neighbors) M19560 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gil207803jgbjM19560jSYN33Ml3C [207803] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 1 MEDLINE link) M19559 Synthetic hybrids; recombinant DNA from bacteriophage M13 and plasmid pHV33 gij207802|gbjMl9559jSYN33M13B [207802] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 227 nucleotide neighbors) M10568 Bacteriophage M13 replicative form II, replication origin, specific nick location gil2l5220gbIM10568|M13ORI [215220] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 650 nucleotide neighbors) M10910 Bacteriophage M13 gene II regulatory region and MI3sjl mutant gij215209jgbjM10910]Ml3IIREG [215209] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 72 nucleotide neighbors) M38295 Bacteriophage M13 HaeII restriction fragment DNA gil2l5208jgbjM38295jM13HAEIHI [215208] (View GenBank report,FASTA report,ASN.1 report,Graphical view, or 67 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 E02067 -210 DNA encoding a part of Bacteriophage M13 tg 127 gil217031 IldbjIE02067E02067 [2170311] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) 102467 Bacteriophage MS2, complete genorne gil2152321gbJ02467|MS2CG [215232] (View GenBank report,FASTA reportASN.1 report,Graphical view,S MEDLINE links, 4 protein links, 20 nucleotide neighbors, or I genome link) AJ004950 Bacteriophage P1 ban gene gil3688226lemblAJO1 1592|BP101 1592 f36882261 (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 1 protein link) U88974 Bacteriophage P1 structural lyric transgiycosylase (orf47), pep44b (orf44b), pep44a (orf44a), and pep43 (orf43) genes, complete cds; and pep42 (orf42) gene, partial cds gil2661099lgblAF0356071AF035607 [2661099] (View GenBank report,FASTA reportASN. 1 report,Graphical view,5 protein links, or 1 nucleotide neighbor) AJ000741 Bacteriophage P1 darA operon gil2462938|emblAJ00074 11BPAJ7641 (2462938] (View GenBank report,FASTA report.ASN.I report,Graphical view,1 MEDLINE link, 10 protein links, or 31 nucleotide neighbors X01828 Bacteriophage P1 recombinase gene cin gil15133|embIX018281MYPlCIN [15133] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 MEDLINE link, I protein link, or 3 nucleotide neighbors) X98146 Bacteriophage P1 DNA sequence around the Op88 operator gil1359513embX98 146|BP1OP880P [1359513] (View GenBank report,FASTA report,ASN.1 report,Graphical view, or 1 nucleotide neighbor) S61175 imrIrl operon: icd=cell division repressor, antl=antirepressor (promoters P5 la, P5lb} [bacteriophage P1, Genomic, 728 nt] gii385908gbIS61175fS61175 [385908] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 MEDLINE link; or 3 nucleotide-neighbors) X87824 Bacteriophage P1 gene 26 gi1861l64IemblX87824jXXEP1G26 [861164] (View GenBank report,FASTA report-ASN.1 reportGraphical view, or 1 protein link) X15638 Phage P1 DNA for lyric replicon containing promoter P53 and two open reading frames gil15735lembIX1563SPPILREP [157351 (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 3 protein links, or 24 nucleotide neighbors WO 00/32825 PCT/IB99/02040 211 X 17512 Bacteriophage P1 DNA for immunity region immI gill 54791embIX I75121P 1 IMMUNIY [15479] (View GenBank report,FASTA report,ASN.1 report,Graphical view,2 MEDLINE links, or 4 nucleotide neighbors) X 16005 Bacteriophage P1 cI gene for PIcI repressor protein gil15477lembIX160051PlCI [15477] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors X03453 Bacteriophage P1 cre gene for recombinase protein gilI5135lembIX03453|MYPICRE [15135] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, 2 protein links, or 12 nucleotide neighbors X06561 Bacteriophage P I cI gene 5-region giI15128jembIX06561|MYPpCl (15128] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 4 protein links, or 6 nucleotide neighbors) V01534 Bacteriophage PI genome fragment (IS2 insertion spot). This regions contains four unidentified reading frames and is known as insertion hot spot for IS2 insertion sequences gi115118|embIV015341MYOVPI [15118] (View GenBank reportFASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 4 protein links, or 3 nucleotide neighbors) X56951 Bacteriophage P1 gene 10 gil406728lembIX569511BPPIGPIO [406728] (View GenBank report,FASTA reportASN.1 reportGraphical view,2 MEDLINE links, 3 protein links, or 1 nucleotide neighbor) K02380 Bacteriophage P1 replication region including repA, parA, and parB genes and incA, incB, and incC incompatibility determinants giI215652|gbIK023801PP IREP [215652] (View GenBank report,FASTA reportASN.1 report,Graphical view,5 MEDLINE links, 4 protein links, or 8 nucleotide neighbors) X87674 Bacteriophage P1 lydA & lydB genes gil 974 7 63lembIX876741BACPILYD [974763] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) X87673 Bacteriophage PI gene 17 gil97476 l|emblX876731BACP 17 [974761] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) M16618 Bacteriophage P1 ci repressor binding sites gil2156001gblM166181PPIC1 [215600] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 3 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 212 SEG PPICIN Bacteriophage P1 cin gene encoding recombinase, cixL recombination site, and 5' end of C invertible element gil2156071gbISEGPP I CIN [215607] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLNE link, 1 protein link, or 4 nucleotide neighbors) K03173 Bacteriophage P1 C invertible element, right end, and cixR recombination site gi|215606igblK031731PP I CIN2 [215606] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) 215605 Bacteriophage P1 cin gene encoding recombinase, cixL recombination site, and 5' end of C invertible element gij2I56051lclfX0 1828 [215605] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M25470 Bacteriophage Pl tail fiber protein gene, complete cds gil3413491gbM254701PP ITFPR [341349] (View GenBank report,FASTA reportASN.I report,Graphical view, 1 MEDLrNE link, 3 protein links, or 3 nucleotide neighbors M34382 Bacteriophage P 1 sim region proteins, complete cds gil2l5661|gbIM343821PP ISIM [215661] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 2 protein links) M81956 Bacteriophage P1 R protein (R) gene, complete cds gil2156581gbjM819561PP1RP [215658] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 4 nucleotide neighbors j M37080 Bacteriophage P1 mini-P 1 plasmid origin of replication gil215657igbIM370801PPI REPOR [215657] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINE link, or 46 nucleotide neighbors) M27041 Bacteriophage P1 ref gene, complete cds gil2156501gbjM270411PPIREF [215650] (View GenBank reportFASTA reportASN.I reportGraphical view,1 MEDLINE link, I protein link, or 1 nucleotide neighbor) L01408 Bacteriophage P1 partition protein (parB) gene, 3' end gil2l5642|gbIL014081PPIPARB [215642] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 protein link, or 41 nucleotide neighbors) SEG PPIPAR Bacteriophage miniplasmid P1 parA gene, 5' end gij215639jgbjlSEGPP IPAR [215639] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 48 nucleotide neighbors) M36425 Bacteriophage miniplasmid P1 parB gene, 3' end giJ215638|gbIM364251PPIPAR2 [215638] (View GenBank reportFASTA reportASN. 1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 M36424 213 Bacteriophage miniplasmid P1 parA gene, 5' end gil215637|gblM364241PP1PAR1 [215637 (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M11129 Bacteriophage P1 miniplasmid origin of replication region giI215632|gbIM 11 1291PP 1ORLM [215632] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 43 nucleotide neighbors) M25414 Bacteriophage P1 c I repressor binding site, operator 88 (Op88) gi1215631|gbjM25414|PPOP88A [215631] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 3 nucleotide neighbors) M25413 Bacteriophage P1 cI repressor binding site, operator 68 (Op68) gi!21563OIgbIM254131PP1OP68A [215630] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 1 MEDLINE link) M25412 Bacteriophage P1 ci repressor binding site, operator 21 (Op 21 ) gil2l56291gbIM25412|PP1OP21A [215629) (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 1 nucleotide neighbor) M10510 Bacteriophage P1 recombination site loxR giJ2156281gblM10510PP1LOXR [215628] (View GenBank reportFASTA report,ASN.1 report,Graphical view, 1 MEDLINE link, or 1 nucleotide neighbor) M10287 Bacteriophage P 1 loxP X loxP recombination site gil2156271gbM10287PPILOXPX [215627] (View GenBank reportFASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 13 nucleotide neighbors) M10494 Bacteriophage P1 recombination site loxP gil2156261gb1M104941PP1LOXP [215626) (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 134 nucleotide neighbors) M10511 Bacteriophage P1 recombination site loxL gil215625|gbIM1051 llPPILOXL [215625] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M10512 Bacteriophage P1 recombination site IoxB gi12156241gbIM105121PPILOXB [215624] (View GenBank report,FASTA reportASN.1 report,Graphical view, or 1 MEDLINE link) M10145 Bacteriophage P1 genome fragment with recombination site loxP giJ2156231gblM101451PP1CREX (215623] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 21 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 M13327 214 Bacteriophage PI Cin recombinase activated cross over site, junction IV, clone pSHI326 gil2156221gbIM133271PP I CN26IV [215622] (View GenBank report,FASTA report,ASN. I report,Graphical view, 1 MEDLINE link, or 7 nucleotide neighbors) M13325 Bacteriophage P1 Cin recombinase activated cross over site, junction II, clone pSHI326 gil21562I|gb|MI33251PPICN261I [215621] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 M4EDLINE link, or 1401 nucleotide neighbors) M13323 Bacteriophage P1 Cin recombinase activated cross over site, junction IV, clone pSHI325 gil2l5620Igb|M13323JPPl1CN25IV [215620] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 7 nucleotide neighbors) M13321 Bacteriophage P1 Cin recombinase activated cross over site, junction II, clone pSHI325 gil2156191gb|M1332 1PPICN25II [215619] (View GenBank report,FASTA reportASN. I report,Graphical view, 1 MEDLINE link, or 1058 nucleotide neighbors) M13324 Bacteriophage P1 Cin recombinase activated cross over site, junction I, clone pSHI326 gil2l5618igblM13324|PP I CIR26I [215618] (View GenBank reportFASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 7 nucleotide neighbors ) M13319 Bacteriophage P1 Cin recombinase activated cross over site, right junction, clone pSHI327 gil215617|gbjM13319PP1 CIN27R [215617] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 7 nucleotide neighbors ) M13320 Bacteriophage P1 Cin recombinase activated cross over site, junction I, clone pSHI325 gil2l5616|gblM133201PPICIN25I [215616] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINE link, or 7 nucleotide neighbors ) M13318 Bacteriophage P1 Cin recombinase activated cross over site, left junction, clone pSHI324 giJ 2 15615|gblM133181PP1CIN24L [215615] (View GenBank reportFASTA reportASN. 1 report,Graphical view,1 IMDLINE link, or 1370 nucleotide neighbors ) M13317 Bacteriophage P1 Cin recombinase activated cross over site, right junction, clone pSHI323 gi1 2 l56141gbIM133171PPICIN23M [215614] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 1055 nucleotide neighbors ) M13316 Bacteriophage P1 Cin recombinase activated cross over site, left junction, clone pSI323 gi|2l5613|gbIM13316|PPICIN23L [215613] (View GenBanik reportFASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 7 nucleotide neighbors ) M13315 Bacteriophage P1 Cin recombinase activated cross over site, right junction, clone pSHI322 gil215612|gblM133151PPICIN22R [215612] (View GenBank reportFASTA reportASN.I reportGraphical view,1 MEDLINE link, or 7 nucleotide neighbors ) WO 00/32825 PCT/IB99/02040 M13314 215 Bacteriophage P1 Cin recombinase activated cross over site, left junction, clone pSHI322 giI21561IgbIM133141PP I CIN22L [215611] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, or 1401 nucleotide neighbors) M13313 Bacteriophage P1 Cin recombinase activated cross over site, right junction, clone pSHI321 giI215610|gbIM13313|PPICIN21R [215610] (View GenBank report,FASTA reportASN.1 report,Graphical view,l MEDLINE link, or 7 nucleotide neighbors) M13312 Bacteriophage P1 Cin recombinase activated cross over site, left junction, clone pSHI321 gil2l56091gbIM133121PPlCIN21L [215609] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 1058 nucleotide neighbors) M 16568 Bacteriophage P1 c4 repressor gene, complete cds gif215603|gbIM165681PPlC4 [215603] (View GenBank report,FASTA reportASN. 1 report,Graphical view,I MEDLINE link, 1 protein link, or 4 nucleotide neighbors) M13326 Bacteriophage P1 Cin recombinase activated cross over site, junction III, clone pSHI326 giJ215602JgbJM13326JPP1C26IE [215602] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 1192 nucleotide neighbors) M13322 Bacteriophage P1 Cin recombinase activated cross over site, junction M, clone pSHI325 gil215601|gb|M13322|PP1C25II [215601] (View GenBank reportFASTA reportASN.1 reportGraphical view,I MEDLINE link, or 1231 nucleotide neighbors) J05651 Bacteriophage P1 modulator protein (bof) gene, complete cds gil215598Jgb|J0565lJPPlBOFYl (215598] (View GenBank report,FASTA reportASN. 1 report,Graphical view, I MEDLINE link, 1 protein link, or 3 nucleotide neighbors) M33224 Bacteriophage P1 regulatory protein (bof) gene, complete cds gil215596|gbIM33224|PPIBOFFO [215596] (View GenBank report,FASTA reportASN. 1 reportGraphical view,] MEDLINE link, 1 protein link, or 3 nucleotide neighbors M10288 E.coli/bacteriophage P1 loxR recombination site gill46647|gbIM10288JECOLOXR [146647] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 3 nucleotide neighbors ) M10289 E.coli/bacteriophage P1 IoxL recombination site gi1466461gbIM10289JECOLOXL [146646] (View GenBank report,FASTA reportASN.1 report,Graphical view,] MEDLINE link, or 2 nucleotide neighbors ) M10290 E.coli loxB site, which can recombine with bacteriophage P1 loxP site gil 146645igbiM10290JECOLO) [146645] (View GenBank report,FASTA reportASN. 1 reportGraphical view,] MEDLINE link, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 216 M10287 Bacteriophage P1 loxP X loxP recombination site gij215627|gbjM10287jPP1 LOXPX [215627] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 13 nucleotide neighbors) M74046 Bacteriophage P1 pacA and pacB genes, complete cds giJ215634lgblM740461PP 1 PACAB [215634] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,1 MEDLINE link, or 2 protein links) M95666 Bacteriophage P1 gene 10, doc and phd genes, complete cds gil 4 63276JgblM95666jPPlPHDDOC [463276] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, 4 protein links, or 1 nucleotide neighbor) M25604 Bacteriophage Q-beta mutated autonomously replicating sequence MDVl RNA fragment gil5563591gbIM25604|PQBARSMUT [556359] (View GenBank report,FASTA report,ASN.1 report,Graphical view,l MEDLINE link, or 8 nucleotide neighbors) V00643 first half of the phage Q-beta gene for coat protein gil 15088|embIV006431LEQBET [15088] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors M25167 Bacteriophage Q-beta RNA fragment recovered from replicase binding complex gil5563621gbIM251671PQBREPLICB [556362] (View GenBank report,FASTA reportASN. 1 reportGraphical view, I MEDLINE link, or 2 nucleotide neighbors) M24876 Bacteriophage Q-beta replicase RNA, 5' end gil5563601gblM24 8761PQBREPLICA [556360] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, I protein link, or 4 nucleotide neighbors) M25444 Synthetic bacteriophage Q-beta DNA gil209118lgblM254441SYNPQBTERM [209118] (View GenBank report,FASTA reportASN. 1 reportGraphical view,1 MEDLINE link, or 8 nucleotide neighbors) A25463 Bacteriophage Q-beta self-replicating microvariant (+)'RNA gil532 4 891gblM25463|PQBMVSRRNA [532489] (View GenBank reportFASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) 425014 Bateriophage Q-beta RNA replicase gene, 5'end, and maturation protein gene, 3' end gil294316|gblM250141PQBREPLC [294316] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors 425065 Bacteriophage Q-beta RNA sequence with putative stem loop gil294315|gbjM25065|PQBLOOP [294315] (View GenBank report,FASTA reportASN. 1 report,Graphical view, I MEDLINE link, or 3 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 217 M10265 Bacteriophage Q-beta RNA molecule with the ability to replicate extracellularly gil2157261gblM102651PQBRNA [215726] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, or 8 nucleotide neighbors ) M24815 Bacteriophage Q-beta specified replicase subunit RNA, gil2157251gbM24815PQBREPL [215725] (View GenBank report,FASTA report,ASN. I report,Graphical view, 1 MEDLINE link, or 4 nucleotide neighbors ) M25461 Bacteriophage Q-beta plus-strand RNA, 5' terrninus gi12L57241gblM25461PQBPSSE [215724] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M25462 Bacteriophage Q-beta plus-strand RNA, 3' terminus gil215 7 23IgbjM25462[PQBPS3E [215723] (View GenBank report,FASTA reportASN.1 reportGraphical view, or 8 nucleotide neighbors) M24871 Bacteriophage Q-beta nanovariant WSIII RNA gijl5722jgblM2487|PQBNVWSIC [215722] (View GenBank reportFASTA report,ASN. 1 reportGraphical view,1 MEDLINE link, or 2 nucleotide neighbors) M24870 Bacteriophage Q-beta nanovariant WSII RNA gil21572 lIgblM24870PQBNVWSIB [215721] (View GenBank report,FASTA reportASN. 1 report,Graphical view, I MEDLINE link, or 2 nucleotide neighbors) M24869 Bacteriophage Q-beta nanovariant WSI RNA gil215720IgbIM248691PQBNVWSIA [215720] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 MEDLINE link, or 2 nucleotide neighbors) M10495 Coliphage Q-beta MDV-1(+) RNA gil2157191gbIM104951PQBMDVIA [215719] (View GenBank report,FASTA reportASN.1 report,Graphical view,l MEDLINE link, or 10 nucleotide neighbors) J02484 bacteriophage qbeta coat protein cistron first half gil2157171gbIJ024841PQBCP5 [215717] (View GenBank reportFASTA reportASN.1 reportGraphical view,1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors) M57754 Bacteriophage Q-beta minus strand RNA, 5' terminus gil2l5 7 161gbIM577541PQBBMS5E [215716] (View GenBank report,FASTA reportASN.1 report,Graphical view, or 8 nucleotide neighbors) M24297 Bacteriophage Q-beta 5-terminal region of the minus strand gil215 7 15|gbM242971PQBEND [215715] (View GenBank report,FASTA report,ASN.I report,Graphical view,I MEDLINE link, or 8 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 M10695 218 Bacteriophage Q-beta, MDV-1 RNA gil2l57141gbIM10695|PQB IR [215714] (View GenBank report,FASTA report,ASN.1 report,Graphical view,2 MEDLINE links, or 12 nucleotide neighbors M24827 Bacteriophage R17 A protein gene, 5'end gil2l6078|gbIM24827|R17RNACIS (216078] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 5 nucleotide neighbors) M24829 Bacteriophage R17 coat protein gene, 5' end gij216075|gbFM24829JRl7CP5 [216075] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 5 nucleotide neighbors) 102488 bacteriophage r17 ma synthetase initiation site gil216080jgbIJ024881R17RNASYN [216080] (View GenBank report,FASTA reportASN.I report,Graphical view,3 MEDLINE links, 2 protein links, or 6 nucleotide neighbors 102487 bacteriophage r17 coat protein initiation site gil2160731gblJ02487|R17COATP [216073] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) 102486 bacteriophage r17 a protein initiation site giJ21607IjgblJ024861R17APROT [216071] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) M24826 Bacteriophage R17 coat protein RNA fragment gil216077gbjM24826|R17CPRAA (216077] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 7 nucleotide neighbors ) M24296 Bacteriophage R17 3'-terminal fragment A RNA gil216070lgbjM24296Rl73TFA [216070] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 9 nucleotide neighbors ) 1TFN structure refinement for a 24-nucleotide ma hairpin, nmr, minimized average structure ribonucleic acid, hairpin, bacteriophage r17 molid: 1; molecule: rl7c; chain: null; engineered: yes gil1942336|pdbl1TFNI [1942336] (View GenBank report,FASTA reportASN.I report,Graphical view, or 1 structure link) 1RPEA ma (5'-d(gpgpgpapcpupgpapcpgpapupcpapcpgp cpapgpupcpupapu-3') (24-mer ma hairpin coat protein binding site for bacteriophage r17) (nmr, mnimized average structure) gi1l4210201pdbllRHTI [1421020] (View GenBank reportFASTA reportASN.l reportGraphical view, or 1 structure link) WO 00/32825 PCT/IB99/02040 2-19 M14428 Bacteriophage SI 3 circular DNA, complete genome gi!2160891gbIM14428IS13CG [216089) (View GenBank report,FASTA report,ASN.1 report,Graphical view,2 MEDLINE links, 12 protein links, 26 nucleotide neighbors, or I genome link) 105393 Bacteriophage Ti DNA N- 6 -adenine-methyltransferase (M.Tl) gene, complete cds gi1l661631gbIJ053931BTlNAMTA [166163] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 2 protein links) L46845 Bacteriophage T2 frd3, frd2 genes, complete cds gi,951387|gbIL468451PT2FRD32G [951387] (View GenBank report,FASTA report,ASN.I report,Graphical view,2 protein links, or 17 nucleotide neighbors) L43611 Bacteriophage T2 fibritin (wac) gene, complete cds gil9038691gbIL436 1 lPT2WAC (903869] (View GenBank report,FASTA report,ASN.1 reportGraphical view,I protein link, or 4 nucleotide neighbors) M24812 Bacteriophage T2 secondary structure RNA sequence gil2157961gblM24812IPT2RNA [215796] (View GenBank reportFASTA reportASN. 1 report,Graphical view,1 MEDLINE link, or 4 nucleotide neighbors) M22342 Bacteriphage T2 DNA-(adenine-N6)methyltransferase (dam) gene, complete cds gil2157921gblM22342jPT2DAM [215792] (View GenBank report,FASTA reportASN.I reportGraphical view,l MEDLINE link, 1 protein link, or 2 nucleotide neighbors) S57515 orf 61.2 (intergenic region between 41 and 611 [bacteriophage T2, Genomic, 323 nt] gil298524|gblS57515|S57515 [298524] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 1 protein link) X05312 Bacteriophage T2 gene 38 for receptor recognizing protein gij15l97jemblX053121MYT2G38 [15197] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 1 protein link) X04442 Bacteriophage T2 gene 37 for receptor recognizing protein gil 15195lembIX04442lMYT2G37 (15195] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 1 protein link) X12460 Bacteriophage T2 gene 32 m.RNA for single-stranded DNA binding protein gill5192lemblX124601MYT2G32 [15192] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 14 nucleotide neighbors) X57797 Bacteriophage T2 gene for gp12 gil14875lemblX565551BT2GPI2 [14875] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I protein link, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 220 X01755 Bacteriophage T2 tail fiber gene 36 gil15189IembIX0I755|MYT2F36 [15189] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or I nucleotide neighbor) M14784 Bacteriophage T3 strain amNG225B right end, tail fiber protein, lysis protein and DNA packaging proteins, complete cds giI2158l~lgbIMl4784jPT3RE [215810] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 9 protein links, or 10 nucleotide neighbors SEGPT3RNAPOL Bacteriophage T3 RNA polymerase III gene, 5' end giI710559!gbjISEGPT3RNAPOL [710559] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) M22610 Bacteriophage T3 RNA polymerase III gene, 3' end gii340722|gb1M22610jPT3RNAPOL2 [340722] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M22609 Bacteriophage T3 RNA polymerase III gene, 5' end gil340721|gbIM226091PT3RNAPOLI [340721] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) X05031 Bacteriophage T3 gene region 1-2.5 with primary origin of replication gill5719embX05031POT3ORI [15719] (View GenBank report,FASTA report,ASN.I report,Graphical view,I MEDLINE link, 11 protein links, or 5 nucleotide neighbors X03964 Bacteriophage T3 early control region pos. 308-8 10 from genome left end giI15718|embbX039641POT3EP [15718] (View GenBank report,FASTA report,ASN.1 report,Graphical view,2 MEDLINE links, or 20 nucleotide neighbors) X17255 Bacteriophage T3 gene I to gene I1 gil15682jembX172551POT31 IIG [15682] (View GenBank report,FASTA reportASN.1 reportGraphical view,4 MEDLINE links, 36 protein links, 17 nucleotide neighbors, or I genome link) X15840 Phage T3 gene 10 gil15625|embIX158401PODT3G1O [15625] (View GenBank reportFASTA reportASN. 1 report,Grapbical view, 1 MEDLINE link, or 3 nucleotide neighbors) X02981 Bacteriophage T3 gene 1 for RNA polymerase gil15561lembIX0298 I1PODOT3P [15561] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors) J02503 bacteriophage t3 5' end, terminally redundant sequence (trs) gi1215816|gbIJO2503IPT3TRS1 [215816] (View GenBank report,FASTA reportASN.1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 221 SEG PT3TRS bacteriophage t3 5' end, terminally redundant sequence (trs) gil2158181gbIlSEGPT3TRS [215818] (View GenBank report,FASTA report,ASN.I report,Graphical view, or 1 MEDLINE link) 102504 bacteriophage t3 3' end, terminally redundant sequence (trs) gij215817jgbjJ02504jPT3TRS2 (215817] (View GenBank report,FASTA report,ASN.I report, or Graphical view3 H YPERLrNK http://www.rs.noda.sut.ac.jp/~kunisawa h t tp://www.rs.noda.sut.ac.jp/~kunisawa Bacteriophage T4 genomic database compiled by Arisaka et al. X95646 Bacteriophage T5 DNA for region 60.5%-71% of the T5 genome gil2791557lemblAJ00119IIBTJO01191 [2791557] (View GenBank report,FASTA report,ASN.I report,Graphical view,7 MEDLINE links, 12 protein links, or 6 nucleotide neighbors) X56847 Bacteriophage T5 genornic region encoding early genes DIO-D15 gi 15407lembIX129301MYTSD10 [15407] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLTNE link, 5 protein links, or 4 nucleotide neighbors AF039886 Bacteriophage T5 subclone T5.5.3r5.18r, single pass sequence, genornic survey sequence gi12811154jgblAF039886|AF039886 [2811154] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF039885 Bacteriophage T5 subclone T5.40f,4 If, single pass sequence, genomic survey sequence gil28111531gblAF039885|AF039885 [2811153] (View GenBank report,FASTA reportASN. I report, or Graphical view) AF039884 Bacteriophage T5 subclone T5.26.fr, single pass sequence, genomic survey sequence gil2811152igblAF0398841AF039884 [2811152] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF039883 Bacteriophage T5 subclone 10-T5.5.7F, single pass sequence, genomic survey sequence gil281115 lfgblAF0398831AF039883 [2811151] (View GenBank report,FASTA reportASN.I report, or Graphical view) AF039882 Bacteriophage T5 subclone 41-T5.5.4BF, single pass sequence, genomic survey sequence gil281l150jgbAF039882jAF039882 [2811150] (View GenBank reportFASTA report,ASN. 1 report, or Graphical view) AF039881 Bacteriophage T5 subclone 39-T5.5.4aF, single pass sequence, genomic survey sequence gil2811149igblAF0398811AF039881 [2811149] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 AF039880 Bacteriophage T5 subelone 19-T5.7.2r, single pass sequence, genornic survey sequence gil2811148gblAF0398801AF039880 [2811148] (View GenBank report,FASTA report,ASN.1 report, or Graphical view) AF039879 Bacteriophage T5 subclone 18-T5.7.2F, single pass sequence, genornic survey sequence gi128111471gbiAF0398791AF039879 [2811147] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF039878 Bacteriophage T5 subclone I1 -T5.5.7R, single pass sequence, genornic survey sequence gil281 I 1461gblAF039878|AF039878 [2811146] (View GenBank report,FASTA report,ASN.1 report,Graphical view, or 2 nucleotide neighbors) AF039877 Bacteriophage TS subclone T5.4FR, single pass sequence, genomic survey sequence gil28111451gblAF0398771AF039877 [2811145] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF039876 Bacteriophage T5 subclone 22-TS.16R, single pass sequence, genornic survey sequence gil2811l44|gbIAF0398761AF039876 [2811144) (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF039875 . Bacteriophage T5 subclone 21-TS.16R, single pass sequence, genomic survey sequence gij281I143|gbjAF039875|AF039875 [2811143] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF039874 Bacteriophage T5 subclone 21-TS.16F, single pass sequence, genomic survey sequence gil2811142igbAF0398741AF039874 [2811142) (View GenBank reportFASTA report,ASN. 1 report, or Graphical view) AF039873 Bacteriophage T5 subcione 09-T5.6F, single pass sequence, genomic survey sequence gil281114l1gblAF039873|AF039873 [2811141) (View GenBank reportFASTA reportASN. 1 report, or Graphical view) AF039872 Bacteriophage T5 subclone 09-T5.6R, single pass sequence, genomic survey sequence gil28 11140gblAF0398721AF039872 [2811140) (View GenBank reportFASTA reportASN. 1 reportGraphical view, or 2 nucleotide neighbors) AF039871 Bacteriophage T5 subclone 04-T5.26.R, single pass sequence, genomic survey sequence gil28111391gblAF039871|AF039871 [2811139] (View GenBank reportFASTA reportASN. 1 report, or Graphical view) AF039870 Bacteriophage TS subclone 13-TS.42F, single pass sequence, genomic survey sequence gil2811138igblAF039870|AF039870 [2811138] (View GenBank reportFASTA reportASN. 1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 223 X69460 Bacteriophage T5 Itf gene for L-shaped tail fibers gil15415|embX69460|M5LTF [15415] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, I protein link, or 4 nucleotide neighbors X03402 Bacteriophage T5 D15 gene for 5' exonuclease gil15413lembIX034021MYTSEXOG [15413] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 MEDLINE link, 1 protein link, or 2 nucleotide neighbors) ZI 1972 Bacteriophage T5 tRNA-Tyr, tRNA-Glu, tRNA-Trp, tRNA-Phe, tRNA-Cys and tRNA-Asn genes, and ORFs 91aa, 90aa, 42aa and 172aa gil15795lembIZl 19721T56TRNAG [15795] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 4 protein links, or 3 nucleotide neighbors) X03898 Bacteriophage T5 genes for tRNA-His, -Ser and -Leu gil15786lemblX038981STTSRNI [15786] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 2 MEDLINE links) X04177 Bacteriophage T5 gene for transfer RNA-Gln gil 15421 lemblX041771MYTSTRNQ [15421] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or 2 nucleotide neighbors) X03899 Bacteriophage T5 genes for tRNA-Val, -Lys, -fMet, -Pro and -Ile3 gill5787|emblX03899jSTT5RN2 (15787] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) X03798 Bacteriophage T5 gene for tRNA-Asp (GUC) gil15472emblX03798|NCTTRDG (15472] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) Y00364 Bacteriophage T5 tRNA gene cluster (27.8%-22.4%) gil15420lemblY00364NMSTRN (15420] (View GenBank reportFASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 13 nucleotide neighbors) X03140 Bacteriophage T5 DNA with rho-dependent transcription terminator (Hind III-P fragment) gil15417IemblX031401MYT5RHO [15417] (View GenBank reportFASTA reportASN.1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) Z35070 Bacteriophage T6 DNA gil535228|embjZ35074|MYEREGBT6 (535228] (View GenBank reportFASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, or 1 protein link) WO 00/32825 PCT/IB99/02040 224 AF060870 Coliphage T6 small subunit distal tail fiber (gene 36) gene, partial cds; and large subunit distal tail fiber (gene 37) and tail fiber adhesin (gene 38) genes, complete cds gil3676458gblAF052605|AF052605 [3676458] (View GenBank report,FASTA reportASN. 1 report,Graphical view,3 protein links, or 2 nucleotide neighbors) Z35072 Bacteriophage T6 DNA encoding ORF19.1 gene and g19 gene gil535232embIZ350721MYTAILT6 [5352321 (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 2 protein links) X12488 Bacteriophage T6 gene 32 mRNA for single-stranded DNA binding protein gilI5843lembX124881MYT6G32 [15843] (View GenBank reportFASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, I protein link, or 14 nucleotide neighbors Z78095 Bacteriophage T6 DNA (1506 bp) gil1488562lembIZ780951BPHZ78095 [1488562] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I protein link, or 4 nucleotide neighbors) Z35079 Bacteriophage T6 DNA for Ip5, Ip6 gi1535215lemblZ35079lMY57BT6 [535215] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) X68725 E.coli bacteriophage T6 gene for beta-glucosyl-HMC-alpha-glucosyl-transferase gil296439IemblX68725ECT6 [296439) (View GenBank report,FASTA reportASN.1 reportGraphical view,I MEDLINE link, 3 protein links, or I nucleotide neighbor) X69894 Bacteriophage T6 alt gene for ADP-Ribosyltransferase gil 5422lemblX69894lMYT6ADP [15422] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, I protein link, or 1 nucleotide neighbor) L46846 Bacteriophage T6 frd3, frd2 genes, complete cds gil9513901gblL468461PT6FRD32G [951390] (View GenBank report,FASTA reportASN.1 reportGraphical view, or 2 protein links) M27738 Bacteriophage T6 translational repressor protein (regA), complete cds gil215993|gblM27738jPT6REGA [215993] (View GenBank reportFASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, I protein link, or 5 nucleotide neighbors ) M38465 Bacteriophage T6 DNA ligase gene, complete cds gil215991|gbIM384651PT6LIG55 [215991] (View GenBank reportFASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 2 nucleotide neighbors ) WO 00/32825 PCT/IB99/02040 225 V01 146 Genome of bacteriophage T7 gil4311871embl VOl 461T7CG [431187] (View GenBank report,FASTA report,ASN.I report,Graphical view,13 MEDLINE links, 60 protein links, 105 nucleotide neighbors, or 1 genome link) X60322 Bacteriophage alpha3 genes A, B, K, C, D, E, J, F, G, H gill4775lemblX603221BACALPHA [14775] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 10 protein links, 22 nucleotide neighbors, or I genome link) X13332 Bacteriophage alpha3 DNA for origin of replication gill5093lemblX133321MIA30RPL [15093] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 1 MEDLINE link) X12611 Bacteriophage alpha3 gene for protein A part., fmger domain gilI50921emblX1261 llMIA3AFIN [15092] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, I protein link, or 6 nucleotide neighbors) X15721 Bacteriophage alpha3 deletion mutation DNA for the origin region (-ori) of replication gill4774lemblX1572 1IBA3DMOR9 [14774] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 11 nucleotide neighbors) X15720 Bacteriophage alpha3 deletion mutant DNA for the origin region (-ori) of replication gil14773|emblXI5720IBA3DMOR8 [14773] (View GenBank reportFASTA reportASN. 1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) X15719 Bacteriophage alpha3 insertion mutant DNA for the origin region (-ori) of replication gill4772lemblX157191BA3DMOR7 [14772] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 10 nucleotide neighbors) X15718 Bacteriophage alpha3 deletion mutation DNA for origin region (-ori) of replication gil 14771 lemblX1 5718IBA3DMOR6 [14771) (View GenBank reportFASTA reportASN. I reportGraphical view, I MEDLINE link, or 11 nucleotide neighbors) X15717 Bacteriophage alpha3 deletion mutant DNA for origin region (-ori) of replication gill4770lemblXl5717jBA3DMOR5 [14770] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,1 IMEDLINE link, or 9 nucleoride neighbors) X15716 Bacteriophage alpha3 deletion mutant DNA for origin region (-ori) of replication gill4769lemblX157161BA3DMOR4 [14769] (View GenBank report,FASTA reportASN.1 reportGraphical view,l MEDLINE link, or 10 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 226 X15715 Bacteriophage alpha3 deletion mutant DNA for origin region (-ori) of of replication gil l4768lemblX157151BA3DMOR3 [14768] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 11 nucleotide neighbors ) X15714 Bacteriophage alpha3 deletion mutant DNA for origin region (-ori) of replication gil14767lemblX157141BA3DMOR2 [14767] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINE link, or 11 nucleotide neighbors ) X15713 Bacteriophage alpha3 deletion mutant DNA for the origin region (-ori) of replication gil l4766lemblX157131BA3DMORl [14766] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, or 11 nucleotide neighbors) X62059 Bacteriophage alpha3 origin of cDNA synthesis (oriGA) gil 1 4 7 63 IemblX620591AL30RIGA [14763] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, or 13 nucleotide neighbors) X62058 Bacteriophage alpha3 origin of cDNA synthesis (oriAA) gil l4762lemblX62058|AL3ORIA [14762] (View GenBank report,FASTA reportASN.I reportGraphical view,I MEDLINE link, or 13 nucleotide neighbors) J02444 Bacteriophage alpha3 origin of DNA replication gil1661031gblJO24441AL3ORI [166103] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 12 nucleotide neighbors) M25640 Bacteriophage alpha-3 H protein gene, complete cds gil1661OlgbIM256401AL3HP [166101] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, I protein link, or 13 nucleotide neighbors) M10631 Bacteriophage alpha-3 cleavage site for phage phi-X174 gene A protein gill 660991gblM 10631 |AL3 CSA [166099] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors) X00774 Bacteriophage alpha-3 gene J sequence gil 15431 |embIX00774INCBA3J (15431] (View GenBank report,FASTA reportASN.I reportGraphical view,I MEDLINE link, 3 protein links, or 2 nucleotide neighbors) M25640 Bacteriophage alpha-3 H protein gene, complete cds gil166I0l|gbM256401AL3HP [166101] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 1 protein link, or 13 nucleotide neighbors) M10631 Bacteriophage alpha-3 cleavage site for phage phi-X174 gene A protein gil l66099|gblM1063 1IALCSA [166099] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 102459 227 Bacteriophage lambda, complete genome gil2151041gbIJ024591LAMCG [215104] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,87 MEDLINE links, 67 protein links, 190 nucleotide neighbors, or 1 genome link) J02482 Bacteriophage phi-X 174, complete genome gil216019[gbIJ02482[PX1CG [216019] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,23'MEDLINE links, 11 protein links, 26 nucleotide neighbors, or 1 genome link) 102454 Bacteriophage G4, complete genome gil2154151gbfJ024541PG4CG [215415] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,6 MEDLrNE links, 11 protein links, 20 nucleotide neighbors or 1 genome link) X60323 Bacteriophage phiK complete genome gil1478118lembIX60323IBPHIKCG [1478118] (View GenBank report,FASTA reportASN.I reportGraphical view,10 protein links, 18 nucleotide neighbors, or 1 genome link) L42820 Bacteriophage BF23 tail protein (hrs) gene, complete cds gil 10486801gblL428201BBFHRS (1048680] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) X54455 Bacteriophage BF23 gene 17 and gene 18 gil14797lemblX544551BF231718G [14797] (View GenBank report,FASTA reportASN.I report,Graphical view,2 protein links, or 2 nucleotide neighbors) M37097 Bacteriophage BF23 DNA, right end of terminal repetition gil166115igblM370971BBFRIGH [166115] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 2 nucleotide neighbors) M37096 Bacteriophage BF23 DNA, left end of terminal repetition gill66114|gbIM370961BBFLEFT [166114] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M37095 Bacteriophage BF23 A2-A3 gene, complete cds, and Al gene, 5' end gil16611OIgbIM370951BBFA2A3 [166110] (View GenBank report,FASTA reportASN.I reportGraphical view,2 MEDLINE links, 3 protein links, or 1 nucleotide neighbor) AF056281 Bacteriophage BF23 clone bf23.mac5/6.1, genomic survey sequence gil3090930|gblAF05628 11AF056281 [3090930] (View GenBank report,FASTA reportASN.1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 228 AF056280 Bacteriophage BF23 clone bf23.mac3, genormic survey sequence gil30909291gblAF056280IAF056280 [3090929] (View GenBank report,FASTA report,ASN.I report, or Graphical view) AF056279 Bacteriophage BF23 clone bf23.mac18/21.34, genomic survey sequence gi! 3 0909281gb|AF0562791AF056 2 79 [3090928] (View Gen.Bank report,FASTA report,ASN. I report, or Graphical view) AF056278 Bacteriophage BF23 clone bf23.mac16/19.33, genornic survey sequence gi!3090927gblAF056278|AF056278 [3090927] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056277 Bacteriophage BF23 clone bf23.mac16/19-33, genomic survey sequence gii 3 090926|gblAF0562771AFO56277 [3090926] (View GenBank report,FASTA report,ASN.1 report, or Graphical view) AF056276 Bacteriophage BF23 clone bf23.mac 12/9-9, genomic survey sequence gil 3 090925|gb|AF056276|AF05627 6 [3090925] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056275 Bacteriophage BF23 clone bf23.mac 11/14-24, genomic survey sequence giJ3090924gblAF056275|AF0562 7 5 [3090924] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF056274 Bacteriophage BF23 clone bf23.57r64r, genonic survey sequence gil3090923|gblAF0562741AF0562 74 [3090923] (View GenBank report,FASTA reportASN.1 reportGraphical view, or 3 nucleotide neighbors AF056273 Bacteriophage BF23 clone bf23.54fr, genomic survey sequence gi!3090922|gb|AF0562731AF056273 [3090922] (View GenBank report,FASTA report,ASN.I report, or Graphical view) AF056272 Bacteriophage BF23 clone bf23.47fr.mac 1017, genomic survey sequence giJ3090921|gblAF056272|AF056272 [3090921] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056271 Bacteriophage BF23 clone bf23.23.66r, genomic survey sequence gil3090920|gb1AF0562 711AF056271 [3090920] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF056270 Bacteriophage BF23 clone bf23.23.64f, genomic survey sequence giJ3090919|gbIAF0562701AF056270 [3090919] (View GenBank report,FASTA report,ASN.1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 229 AF056269 Bacteriophage BF23 clone bf23.23.60r, genomic survey sequence gil3090918|gbjAF056269jAF056269 [3090918] (View GenBank report,FASTA report,ASN.1 report, or Graphical view) AF056268 Bacteriophage BF23 clone bf23.23.60f, genomic survey sequence gil3090917|gb1AF056268|AF056268 [3090917] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, or 1 nucleotde neighbor AF056267 Bacteriophage BF23 clone bf23.23.59r, genomic survey sequence gil3090916|gblAF056267|AF056267 [3090916] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056266 Bacteriophage BF23 clone bf23.23.59f, genomic survey sequence gil30909151gbIAF0562661AF056266 [3090915] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056265 Bacteriophage BF23 clone bf23.23.56r, genomic survey sequence gi13090914|gb1AF0562651AF056265 [3090914] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056264 Bacteriophage BF23 clone bf23.23.56f, genomic survey sequence gi130909131gblAF056264|AF056264 [3090913] (View GenBank reportFASTA reportASN. 1 report, or Graphical view) AF056263 Bacteriophage BF23 clone bf23.23.68f55r, genornic survey sequence gi|3090912IgblAF0562631AF056263 [3090912 (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF056262 Bacteriophage BF23 clone bf23.23.43fr.66f, genomic survey sequence giJ3090911 |gblAF0562621AF056262 [3090911] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056261 Bacteriophage BF23 clone bf23.23.2fr, genomic survey sequence giJ3090910jgb1AF056261|AF056261 [3090910] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056260 Bacteriophage BF23 clone bf23.23.55.f, genornic survey sequence giI30909091gb|AF0562601AF056260 [3090909] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056259 Bacteriophage BF23 clone bf23.23.53.r, genomic survey sequence giJ3090908|gblAF056259|AF056259 [3090908] (View GenBank report,FASTA reportASN.1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 230 AF056258 Bacteriophage BF23 clone bf23.23.53.f, genomic survey sequence giJ3090907|gb1AF0562581AF056258 [3090907] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056257 Bacteriophage BF23 clone bf23.23.52.r, genornic survey sequence gil3090906|gb|AF0562571AF056257 [3090906] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056256 Bacteriophage BF23 clone bf23.23.52.f, genomic survey sequence gil3090905gbjAF056256jAF056256 [3090905] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056255 Bacteriophage BF23 clone bf23.23.49.r, genomic survey sequence gi!3090904|gbIAF0562551AF056255 [3090904] (View GenBank report,FASTA report,ASN.I report, or Graphical view) AF056254 Bacteriophage BF23 clone bf23.23.49.f, genomic survey sequence giJ3090903|gb|AF056254|AF056254 [3090903] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056253 Bacteriophage BF23 clone bf23.23.48.r, genomic survey sequence gil3090902|gb|AF056253|AF056253 [3090902] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) AF056252 Bacteriophage BF23 clone bf23.23.48.f, genonic survey sequence giJ3090901|gbjAF0562521AF056252 (3090901] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF056251 Bacteriophage BF23 clone bf23.23.44.r, genomic survey sequence gil30909001gb1AF0562511AF056251 (3090900] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056250 Bacteriophage BF23 clone bf23.23.41.f, genomic survey sequence gi|30908991gb1AF0562501AF056250 [3090899] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) AF056249 Bacteriophage BF23 clone bf23.23.22.a.r, genomic survey sequence gi13O9O898|gblAF056249|AF056249 [3090898] (View GenBank report,FASTA reportASN.1 report, or Graphical view) AF056248 Bacteriophage BF23 clone bf23.23.22.a.f, genomic survey sequence gi3090897|gb1AF0562481AF056248 (3090897] (View GenBank reportFASTA reportASN. 1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 AF056247 231 Bacteriophage BF23 clone bf23.23.68.r, genornic survey sequence gil3090896|gbIAF0562471AF056247 [3090896] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) Z50114 Bacteriophage BF23 DNA for putative tail protein gene giJ2464952fembIZ501141BF23LATE [2464952] (View GenBank repori,FASTA report,ASN. 1 report,Graphical view, or 1 protein link) D12824 Bacteriophage BF23 genes for minor tail protein gp24 and major tail protein gp25, complete cds gil520578|dbjlDl2824JBBF2TAIL [520578] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 3 nucleotide neighbors) Z34953 Bacteriophage K3 ip9, ip7 and ip8 genes gil53526lJembZ34953JMYK3IP 97 8 [535261] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 3 protein links, or 1 nucleotide neighbor) Z35075 Bacteriophage K3 DNA for Ip3 and Ip4 gil535229embZ35075fMYEORF64K [535229] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 2 protein links) X05560 Bacteriophage K3 gene 38 for receptor recognizing protein gil15112lemblX055601MYK3G38 [15112] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, or I protein link) X04747 Bacteriophage K3 gene 37 for receptor recognizing protein gill5! 10lembIX04747|MYK3G37 (15110] (View GenBank report,FASTA reportASN. 1 reportGraphical view, I MEDLINE link, I protein link, or 2 nucleotide neighbors) X01754 Bacteriophage K3 tail fiber gene 36 gilI5l8OlemblX01754MYK3F36 [15108] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, or 2 protein links) M16812 Bacteriophage K3 t' lysis gene, complete cds giJl5503|gbJl6812JPK3LYST [215503] (View GenBank report,FASTA reportASN. 1 reportGraphical view,I MEDLINE link, 1 protein link, or 4 nucleotide neighbors) L46833 Bacteriophage K3 frd3, frd2 genes, complete cds gil951377|gbJL46833JPK3FRD32G [951377] (View GenBank report,FASTA reportASN. 1 reportGraphical view,2 protein links, or 2 nucleotide neighbors) L43613 Bacteriophage K3 fibritin (wac) gene, complete cds giJ90386lgbL436l3JPK3WAC [903861] (View GenBank report,FASTA report,ASN.1 reportGraphical view,1 protein link, or 4 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 232 X01753 Bacteriophage Ox2 tail fiber gene 36 gil15122lernblX017531MYOX2F3 6 [15122] (View Gen.Bank report,FASTA report,ASN. I reportGraphical view, I MEDLINE link, 2 protein links, or 1 nucleotide neighbor) L43612 Bacteriophage Ox2 fibritin (wac) gene, complete cds gil 9 0 3 848|gbL436121OX2WAC [903848] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I protein link, or 4 nucleotide neighbors) Z46880 Bacteriophage OX2 stp gene gil5 9 96 63 lemblZ468801BPOX2STP [599663] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, I protein link, or 4 nucleotide neighbors) X05675 Bacteriophage Ox2 gene 38 for receptor-recognizing protein and flanking regions gijl5l24|ernbfX05675sMYOX2G 3 8 [15124] (View GenBank report,FASTA report,ASN. I reportGraphical view, I MEDLINE link, 3 protein links, or I nucleotide neighbor) M33533 Bacteriophage RB18 translational repressor protein (regA) and Orf43.1, complete cds gi!216083|gblM33533|RB18REGA [216083] (View GenfBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINE link, 2 protein links, or 2 nucleotide neighbors AF033329 Bacteriophage RB 18 single-stranded binding protein (gene 32) gene, partial cds, and 5' region gil 2 6457881gblAF0333291AQ 33 32 9 (2645788] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 protein link, or I1 nucleotide neighbors) M86231 Bacteriophage RB69 gene 62, 3'end; RegA (regA) gene, complete cds gil215354|gblM8623 IIP6962REGA [215354] (View GenBank reportFASTA reportASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 1 nucleotide neighbor) AF033332 Bacteriophage RB69 single-stranded binding protein (gene 32) gene, partial cds, and 5' region gil2645794gblAF0333321AF0 3 3 33 2 (2645794) (View GenBank reportFASTA reportASN.1 reportGraphical view,1 protein link, or 12 nucleotide neighbors) U34036 Bacteriophage RB69 DNA polymerase (43) gene, complete cds gil12371251gbIU340361BRU34036 [1237125] (View GenBank reportFASTA reportASN. 1 report,Graphical view,1 MEDLINE link, or 1 protein link) V01145 Bacteriophage HI genome fragment Each Thymine given in this sequence represents a HMU-residue (HMIJ = 5-hydroxyrnethyluracil) gil15557jemblV011451PODOHI [15557] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) K05676 Bacteriophage M1 gene 38 for receptor recognizing protein and flanking regions gilI5114IembIX05676IMYMIG38 [15114] (View GenBank reportFASTA reportASN. 1 report,Graphical view, I MEDLINE link, 3 protein links, or I nucleotide neighbor) WO 00/32825 PCT/IB99/02040 233 AF034575 Bacteriophage Ml putative integrase (int) gene, complete cds, and artP region, complete sequence gil2662472|gblAF0345751AF034575 [2662472] (View GenBank report,FASTA report,ASN.1 report,Graphical view, 1 MEDLINE link, or 1 protein link) AF033321 Bacteriophage Ml single-stranded binding protein (gene 32) gene, partial cds, and 5' region gil2645772igblAF0333211AF033 3 2 1 [2645772] (View GenBank report,FASTA report,ASN.1 report,Graphical view,l protein link, or 17 nucleotide neighbors) X55190 Bacteriophage Tula 37 and 38 genes for receptor-recognizing proteins 37 and 38 (respectively), partial cds gil 14860lembIX551I901BPTUIA [14860] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 2 nucleotide neighbors) AF033334 Bacteriophage TuIb single-stranded binding protein (gene 32) gene, partial cds, and 5' region gil26457981gblAF033334|AF033334 [2645798] (View GenBank report,FASTA report,ASN. I report,Graphical view, or 5 nucleotide neighbors) X55191 Bacteriophage Turb 37 gene for receptor-recognizing protein 37 (partial cds), 38 gene for receptor-recognizing protein 38, and t gene (partial cds) gill4863|emblX551911BPTUIB [14863] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 3 protein links, or 3 nucleotide neighbors ) X13065 Bacteriophage phi8O early region gil14800lemblXl 30651BP80ER [14800] (View GenBank report,FASTA report,ASN. I report,Graphical view, I MEDLINE link, 8 protein links, or 6 nucleotide neighbors ) D00360 Bacteriophage phi80 cor gene gil217782|dbjlD00360|P8080COR [217782] (View GenBank report,FASTA report,ASN.1 report,Graphical view, or 1 protein link) X01639 Bacteriophage phi 80 DNA-fragment with replication origin gil15828|emblX016391XCXPHI80 [15828] (View GenBank report,FASTA reportASN. I reportGraphical view, 1 MEDLINE link, or 25 nucleotide neighbors) X04051 Lambdoid bacteriophage phi 80 int-xis region (integrase-excisionase region) gil15770lemblX0405 1ISTPHI80X [15770] (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, 2 protein links, or 1 nucleotide neighbor) X06751 Phage Phi8O DNA for major coat protein gil15768JemblX0675 IISTPHI80C [15768] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or I1 nucleotide neighbors) X75949 Bacteriophage phi8O DNA for ORF x171.8 and ORF x171.28' gil45881 Ilemb|X759491ECORF171B [458811] (View GenBank reportFASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or 28 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 234 L40418 Bacteriophage phi-80 gene, complete cds gil1019107|gb|L40418IP80A [1019107] (View GenBank report,FASTA report,ASN. I report,Graphical view, 1 MEDLINE link, or 1 protein link) M24831 Bacteriophage phi-80 Tyr-tRNA gene, 3 end gi!215363|gbJM2483 I P80TGY [215363] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 43 nucleotide neighbors) M10670 Bacteriophage phi-SO replication origin gi!2153611gblM106701P800RI (215361] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) M24825 Bacteriophage phi-SO RNA fragment gil2l536OIgblM24825jP8OM3A [215360] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or I nucleotide neighbor) M11919 Bacteriophage phi-80 cI immunity region encoding the N gene gil2153581gblM 11919IP80CI [215358] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 2 nucleotide neighbors M10891 Bacteriophage phi-80 attP site DNA gil215357jgbjM1O891poP80ATP [215357] (View GenBank report,FASTA report,ASN.1 report,Graphical view,1 MEDLINE link, or 1 nucleotide neighbor) M19473 Bacteriophage 933J (from E.coli) proviral Shiga-like toxin type 1 subunits A and B genes, complete cds gil215072|gbJM19473IJ93SLTI [215072] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, 2 protein links, or 20 nucleotide neighbors) Y10775 Bacteriophage 933W ileX, stx2A and stx2B genes gil1938206|emblYl 07751BP933ILEX [1938206] (View GenBank report,FASTA reportASN.1 reportGraphical view,2 protein links, or 36 nucleotide neighbors) X83722 Bacteriophage 933W slt-IIB gene gil 14 9 0 2 29|embIX83722B933WSLT [1490229] (View GenBank reportFASTA reportASN.1 reportGraphical view,2 protein links, or 20 nucleotide neighbors) X07865 Bacteriophage 933W slt-II gene for Shiga-like toxin typeII subunit A and B gil14892lemblX078651BWSLTII [14892] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 protein links, or 29 nucleotide neighbors) M16625 Bacteriophage H19B (from E.coli) sltIA and sltIB genes encoding Shiga-like toxin I subunits A and B, complete cds gil2l5O43|gblM16625|H19BSLT [215043] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 24 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 M17358 235 Bacteriophage H19B shiga-like toxin-I (SLT- 1) A and B subunit DNA, complete cds gil2l5046jgbjMl7358|Hl9BSLTA [215046] (View GenBank report,FASTA report,ASN. I report,Graphical view,I MEDLINE link, 2 protein links, or 20 nucleotide neighbors) U29728 Bacteriophage N4 single-stranded DNA-binding protein (N4SSB) gene, complete cds gil939708|gbjU29728|BNU29728 [939708] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, or 1 protein link) J02580 Bacteriophage PA-2 (E.coli porcine strain isolate) Rz gene, 5'end; ORF2, outer membrane porin protein (1c) and ORFI genes. complete cds gil2l53661gbIJ025801PA2LC (215366] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 4 protein links, or 4 nucleotide neighbors) U32222 Bacteriophage 186, complete sequence gil3337249)gbIU322221BIU32222 [3337249] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,6 MEDLINE links, 46 protein links, or 5 nucleotide neighbors) X51522 Bacteriophage P4 complete DNA genome gil450916lemblX515221MYP4CG [450916] (View GenBank reportFASTA report,ASN. 1 report,Graphical view,3 MEDLINE links, 13 protein links, 6 nucleotide neighbors. or 1 genome link) X92588 Bacteriophage 82 orf33, orfl51, orf56, orf96, rus, orf45, and Q genes gil105111 IembIX925881BAC82HOLL [1051111] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,7 protein links, or 1 nucleotide neighbor) J02803 Bacteriophage 82 antitermination protein (Q) gene, complete cds gil2l5364gbIJ02803|P82Q [215364] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINElink, or 1 protein link) U02466 Bacteriophage HK022 (cro), (clI) and (0) genes, complete cds, (P) gene, partial cds gil4072851gbIU024661BHU02466 [407285] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 5 protein links, or 1 nucleotide neighbor) M26291 Bacteriophage D108 regulatory DNA-binding protein (ner) gene, complete cds gil166194|gbIM26291 D18NER [166194] (View GenBank reportFASTA reportASN.1 reportGraphical view,l MEDLINE link, 1 protein link, or 1 nucleotide neighbor) M11272 Bacteriophage D108 left-end DNA gil1661931gbjM 112721D18LEDNA [166193] (View GenBank reportFASTA report,ASN. I report,Graphical view, 1 MEDLINE link, or 2 nucleotide neighbors) Ml8902 Bacteriophage D108 kil gene encoding a replication protein, 3' end; and containing three ORFs, complete cds gill661911gbIM18902ID18KIL [166191] (View GenBank reportFASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors WO 00/32825 PCT/IB99/02040 236 M10191 Bacteriophage D108, left end with Mu A protein binding sites LI and L2 gill66190IgbIM10191ID18SSL [166190] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, or 5 nucleotide neighbors) J02447 bacteriophage d108 gene a 5' end gil l66189|gblJ024471D I 8AAA [166189] (View GenBank report,FASTA report,ASN.1 reportGraphical view, or1 MEDLINE link) V00865 Bacteriophage D108 fragment from genes A and ner (C-terminus of ner and N-terminus of A) giIl5437embjV00865|NCD108 [15437] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 2 protein links) XO 1914 Bacteriophage IKe gene for DNA binding protein gil 14957lembIX019141INIKEDBP [14957] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 2 nucleotide neighbors AF064539 Bacteriophage N15, complete genome gil31926831gblAF064539|AF064539 [3192683] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,2 MEDLINE links, 60 protein links, 26 nucleotide neighbors, or I genome link) U02303 Bacteriophage Ifl, complete genome gil3676280IgbIU02303|B2UO2303 [3676280] (View GenBank report,FASTA reportASN.1 report,Graphical view,10 protein links, or 1 genome link) AF007792 Bacteriophage Mu late morphogenetic region gi135517751gblAF0077921AF007792 [3551775] (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 1 nucleotide neighbor) U24159 Bacteriophage HPI strain HPIc1, complete genome gil1046235|gbU24159|BHU24159 [1046235] (View GenBank report,FASTA reportASN.1 reportGraphical view,6 MEDLINE links, 41 protein links, 8 nucleotide neighbors, or 1 genome link) Z71579 Bacteriophage S2 type A 5.6 kb DNA fragment gill 67 9806lemblZ715791BPiSIlADNA [1679806] (View GenBank report,FASTA reportASN.1 report,Graphical view,3 MEDLINE links, 9 protein links, or 9 nucleotide neighbors X53238 Klebsiella sp. bacteriophage KI 1 gene 1 for RNA polymerase gill4984|emblX532381KSK IIRPO [14984] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 237 X85010 Bacteriophage A5 11 ply5l I gene gil853748|emblX850101BPA51 IPLY [853748] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 3 protein links, or I nucleotide neighbor) U29728 Bacteriophage N4 single-stranded DNA-binding protein (N4SSB) gene, complete cds giI9397081gblU29728lBNU29728 [939708] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 1IEDLINE links, or 1 protein link) 102445 bacteriophage bol 3'-terminal region ma gill661521gblJ024451BO1TR3 [166152] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 5 nucleotide neighbors) L06183 Bacteriophage L5 (from Leuconostoc oenos) genome gil 2 893531gbIL061831BL5GENM [289353] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, or 1 genome link) AF074945 Mycoplasma arthritidis bacteriophage MAVI, complete genome gil3511243|gblAF074945|AF074945 [3511243] (View GenBank report,FASTA reportASN.1 report,Graphical view,15 protein links, 3 nucleotide neighbors, or I genome link) L13696 Bacteriophage L2 (from Mycoplasma), complete genome gil2893381gblL 136961BL2CG [289338] (View GenBank report,FASTA reportASN.1 reportGraphical view,3 MEDLINE links, 14 protein links, or 1 genome link) X80191 Bacteriophage PP7 mRNA for maturation, coat, lysis and replicase proteins gil5172371emb1X80191|BPP7PR [517237] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 4 protein links, or I genome link) M19377 Bacteriophage Pf3 from Pseudomonas aeruginosa (New York strain), complete genome gil2l5380jgbjMl9377jPF3COMNY [215380] (View GenBank reportFASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 9 protein links, or 5 nucleotide neighbors) M11912 Bacteriophage Pf3 from Pseudomonas aeruginosa (Nijmegen strain), complete genome gil2153711gblMI 19121PF3COMN [215371] (View GenBank report,FAS.TA reportASN. I reportGraphical view, 1 MEDLINE link, 9 protein links, 5 nucleotide neighbors, or I genome link) V00605 Bacteriophage Pfl gene encoding DNA binding protein gill 4 970lembIV006051INOPF I [14970] (View GenBank report,FASTA report,ASN.1 reportGraphical view, 1 proteine link, or I nucleotide neighbor) L05626 Bacteriophage PR4 capsid protein (P6) gene, complete cds gil 2 l5735jgbjL05626jPR4P6MAJA [215735] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 ~238 D13409 Bacteriophage phiCTX (isolated from Pseudomonas aeruginosa) cosR, attP, int genes gil217776|dbj!D I3409jBPHCOSR [217776] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 3 protein links, or 3 nucleotide neighbors) D13408 Bacteriophage phiCTX (isolated from Pseudomonas aeruginosa) cosL, ctx genes gil217775!dbjlD134081BPHCOSLCTX [217775] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, or 3 nucleotide neighbors) M24832 Bacteriophage f2 coat protein gene, partial cds gill 6 62 2 81gbIM24832IF2CRNACA [166228] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors S72011 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes,partial cds gil2618967|gblAF0176291AF017629 [2618967] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINElink, 2 protein links, or 44 nucleotide neighbors) AF017628 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618964|gb|AF017628|AF017628 [2618964] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINElink, 2 protein links, or 44 nucleotide neighbors) AF017627 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618961igblAF0176271AF017627 [2618961] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINElink, 2 protein links, or 44 nucleotide neighbors) AF017626 Bacteriophage 21 isocitrate dehydrogenase (icd) gene, partial cds; and integrase (int) gene, partial cds gil26189581gblAF017626|AF017626 [2618958] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 49 nucleotide neighbors) AF017625 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil 2 618955IgblAFO176251AFO17625 [2618955] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINElink, 2 protein links, or 44 nucleotide neighbors) AF017624 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int)genes, partial cds gil2618952igblAF0176241AF017624 (2618952] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINElink, 2 protein links, or 44 nucleotide neighbors) AF017623 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618949igblAF0176231AF017623 [2618949] (View GenBank report,FASTA reportASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 44 nucleotide neighbors) AF017622 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618946|gbIAFO176221AF017622 [2618946] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 AF017621 239 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil26189431gblAF0176211AF01762 1 [2618943] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors D26449 Bacteriophage PS 17 Fl gene for tail sheath protein (gpFI) and FII gene for tail tube protein (gpFl), complete cds gil452l62jdbjjD26449jBPSFIFI [452162] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 2 protein links) X87627 Bacteriophage D3112 A and B genes gil974768lemblX876271BPD3112AB [974768] (View GenBank report,FASTA report,ASN.I report,Graphical view,l MEDLINElink, 2 protein links, or 1 nucleotide neighbor) U32623 Bacteriophage D3 transcriptional activator CII (clI) gene, complete cds gil984852fgbIU326231BDU32623 [984852] (View GenBank report,FASTA report,ASN.I reportGraphical view,I protein link, or 1 nucleotide neighbor) L34781 Bacteriophage phi 1 I holin homologue (ORF3) gene, complete cds and peptidoglycan hydrolase (lytA) gene, partial cds gil5118381gbL347811BPHHOLIN [511838] (View GenBank reportFASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 4 protein links, or 2 nucleotide neighbors ) L14810 Bacteriophage P22 (gp 10) gene, complete cds, and (gp26) gene, complete cds gil2940531gblL 14810P22GP1026X [294053] (View GenBank report,FASTA reportASN. I reportGraphical view,! MEDLINE link, 2 protein links, or 2 nucleotide neighbors ) X87420 Bacteriophage ES18 genes 24, c2, cro, c1, 18, and oL and oR operators gil l 1 4 3407lemblX87420BPES I 8GEN (1143407] (View GenBank reportFASTA report,ASN. 1 reportGraphical view,5 protein links, or 9 nucleotide neighbors) L42820 Bacteriophage BF23 tail protein (hrs) gene, complete cds gilI04868OgbL428201BBFHRS [1048680] (View GenBank report,FASTA reportASN.I reportGraphical view,! IMEDLINElink, 1 protein link, or 1 nucleotide neighbor) X14980 Bacteriophage PRD I XV gene for protein P15 (lytic enzyme) gil15802lembX149801TEPRDIXV [15802] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINElink, 1 protein link, or 4 nucleotide neighbors) X06321 Bacteriophage PRD 1 gene 8 for DNA terminal protein gil15800lembIX063211TEPRD18 [15800) (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, 2 protein links, or 10 nucleotide neighbors) X14336 Filamentous Bacteriophage 12-2 genome gil 14920lemblX143361INBI22 [14920] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,! MEDLINE link, 9 protein links, 1 nucleotide neighbor, or I genome link) WO 00/32825 PCT/IB99/02040 L05001 240 Bacteriophage X glucosyl transferase gene, complete cds gil216044|gbLO501IPXFCLUSYLT [216044] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or I protein link) M29479 Bacteriophage p4 sid and psu genes partial cds, and delta gene, complete cds gi12157011 gblM294791PP4SDP [215701] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,3 protein links, or 4 nucleotide neighbors) SEGPP4PSUSID Bacteriophage P4 capsid size determination protein (sid) gene, 5' end gil215698gbIlSEGPP4PSUSI [215698] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 1 nucleotide neighbor) M29650 Bacteriophage P4 polarity suppression protein (psu) gene, complete cds gil2156971gbIM296501PP4PSUSID2 [215697] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M29651 Bacteriophage P4 capsid size determination protein (sid) gene, 5' end gil2l56961gbIM296511PP4PSUSIDI [215696] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) M27748 Bacteriophage P4 gop, beta, and clI genes, complete cds and int gene, 3' end gil215691|gbIM277481PP4GOPBC [215691) (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 4 protein links, or 1 nucleotide neighbor) K02750 Bacteriophage IKe, complete genome gil215061|gbIK027501IKECG [215061] (View GenBank report,FASTA reportASN.I report,Graphical view,I MEDLINElink, 10 protein links, 4 nucleotide neighbors, or I genome link) L40418 Bacteriophage phi-80 gene, complete cds gil1019107|gbIL40418|P80A [1019107] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 NEDLINE link, or 1 protein link) AF032122 Bacteriophage SfII integrase (int) gene, partial cds; and bactoprenol glucosyl transferase (bgt), and glucosyl tranferase II (gtrII) genes,complete cds gil2465412|gblAF0213471AF021347 [2465412] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINElink, 4 protein links, or 2 nucleotide neighbors) q35825 Bacteriophage SF6 fragment D lysozyme gene, complete cds gij2161 05gbjM35825|SF6LYZ [216105] (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 1 protein link) 35479 Bacteriophage C16 ipI gene gil534936|embZ35479IBC161PI [534936] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, I protein link, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 241 X12638 Bacteriophage 21 DNA for gene 2 gi|296141|embIX12638|B21GENE2 [296141) (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or 1 nucleotide neighbor) X02501 Bacteriophage 21 DNA for left end sequence with genes 1 and 2 gi|15825|emblX0250 11XXPHA21 [15825] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 3 nucleotide neighbors) M65239 Bacteriophage 21 lysis genes S, R, and Rz, complete cds gil215466|gbIM652391PH2LYSGEN [215466] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 3 protein links, or 1 nucleotide neighbor) M58702 Bacteriophage 21 late gene regulatory region gil215465|gblM587021PH2LATEGE [215465] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 MEDLINE link) M81255 Bacteriophage 21 head gene operon gil2154541gbjM812551PH2HEADTL [215454] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,2 MEDLINE links, 10 protein links, or 4 nucleotide neighbors) M23775 Bacteriophage 21 glycoprotein 1 gene, complete cds, and glycoprotein gene, 5' end gil2l545l|gblM23775jPH2GPA [215451] (View GenBank reportFASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 3 nucleotide neighbors) M61865 Bacteriophage 21 excisionase (xis), integrase (int) and isocitrate dehydrogenase (icd), complete cds gil215448|gblM618651PH22XISAA [215448] (View GenBank report,FASTA reportASN. 1 reportGraphical view,2 protein links, or 9 nucleotide neighbors) S72011 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618967]gblAF0176291AF017629 [2618967] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors ) AF017628 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil26189641gblAF0176281AF017628 [2618964] (View GenBank reportFASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors ) AF017627 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil261896l1gblAF0176271AF017627 [2618961] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors) AF017626 Bacteriophage 21 isocitrate dehydrogenase (icd) gene, partial cds; and integrase (int) gene, partial eds gil2618958|gblAF0176261AF017626 [2618958] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 49 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 AF017625 742 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gi12618955igblAF0176251AF017625 [2618955] (View GenBank report,FASTA report,ASN. I report,Graphical view, I MEDLINE link, 2 protein links, or 44 nucleotide neighbors AF017624 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618952|gblAFO176241AF0 176 24 [2618952] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, 2 protein links, or 44 nucleotide neighbors) AFO 17623 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil 26 189491gblAF017623fAF0176 23 [2618949] (View GenfBank report,FASTA report,ASN. 1 report,Graphical view, I MEDLINE link, 2 protein links, or 44 nucleotide neighbors) AF017622 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil2618946igblAF0 17622IAF017622 [2618946] (View GenBank report,FASTA reportASN. I report,Graphical view, I MEDLINE link, 2 protein links, or 44 nucleotide neighbors) AF017621 Bacteriophage 21 isocitrate dehydrogenase (icd) and integrase (int) genes, partial cds gil 2 6 18943|gblAF017621|AF017 62 1 [2618943] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, I MEDLINE link, 2 protein links, or 44 nucleotide neighbors) M57455 Bacteriophage 42D (clone pDB17) (from Staphylococcus aureus) staphylokinase gene, complete cds gil2 lS344jgbMs7455jP42S-1K [215344] (View GenBanik reportFASTA report,ASN. 1 report,Graphical view, I protein link, or 9 nucleotide neighbors) Y12633 Bacteriophage 85 DNA, promoter sequence of unknown gene gil 2 058285|emblYI2633IB85PROM [2058285] (View GenBank report,FASTA reportASN. 1 report, or Graphical view) X98146 Bacteriophage PI DNA sequence around the Op88 operator gil1359513lembX981461BPlOP880P [1359513] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 1 nucleotide neighbor) Y07739 Staphylococcus phage Twort holTW, plyTW genes gil2764979|emblY077391BPTWGHOLG [2764979] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or 2 protein links) L07580 Bacteriophage phi- I1 rinA and rin B genes, required for the activation of Staphylococcal phage phi-il int expression gil 166160gbIL07580|BPHRINAB3 [166160) (View GenBank report,FASTA reportASN. 1 reportGraphical view, I MEDLINE link, or 2 protein links) M34832 Bacteriophage phi-Il integrase (int) and excisionase (xis) genes, complete cds gil1661571gbIM348321BPHINTXIS [166157] (View GenBank report,FASTA reportASN. 1 report,Graphical view,I MEDLINE link, 2 protein links, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 243 M20394 Bacteriophage phi-11 S.aureus attachment site (attP) gil 1661561gblM20394|BPHA TTP [166156] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 MEDLINE link, or 4 nucleotide neighbors) X23128 Bacteriophage phi-13 integrase gene gil758228lemblX823121PH1Il3rNT [758228] (View GenBank report,FASTA report,ASN. 1 report,Graphical view, 1 protein link, or 3 nucleotide neighbors) X61719 S.aureus phi- 13 lysogen right chromosome/bacteriophage DNA junction gil46625lemblX61719ISAP13RJNC [46625] (View GenBank report,FASTA report,ASN. I report,Graphical view, or 1 MEDLINE link) X61718 S.aureus phi-13 lysogen left chromosomal/bacteriophage DNA junction gil46624lemblX617181SAP13LJNC [46624] (View GenBank report,FASTA reportASN. 1 reportGraphical view, or I MEDLINE link) X61717 Bacteriophage phi- 13 core sequence for attachment gil14799lembIX617171BP13A TTP [14799] (View GenBank report,FASTA reportASN. 1 report,Graphical view,2 MEDLINE links, or 3 nucleotide neighbors) U01875 Bacteriophage phi- 13 putative regulatatory region and integrase (int) gene, partial cds gil437118gbIU01875JU01875 [437118] (View GenBank report,FASTA reportASN. 1 reportGraphical view,3 MEDLINE links, or 4 nucleotide neighbors) X67739 S.aureus Bacteriophage phi-42 attP gene gil 4 809lemblX677391BPATTPA [14809] (View GenBank report,FASTA report,ASN. 1 reportGraphical view, 1 MEDLINE link, or 3 nucleotide neighbors) U01872 Bacteriophage phi-42 integrase (int) gene, complete cds gi14371151gblU01872JU01872 [437115] (View GenBank report,FASTA reportASN.I reportGraphical view,3 MEDLINE links, 2 protein links, or 3 nucleotide neighbors) X94423 Staphylococcus aureus bacteriophage phi-42 DNA with OR.Fs (restriction modification system) gil17715 9 7lemblX944231SARMS [1771597] (View GenBank reportFASTA reportASN. 1 report,Graphical view,2 protein links, or 1 nucleotide neighbor) M27965 Bacteriophage L54a (from S.aureus) int and xis genes, complete cds giJ215096JgblM27965L54rNTXIS [215096] (View GenBank reportFASTA reportASN. 1 report,Graphical view, MEDLINE I link, 2 protein links, or 3 nucleotide neighbors) U72397 Bacteriophage 80 alpha holin and amidase genes, complete cds gil1763241|gblU72397|B8U72397 [1763241] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,2 protein links, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 244 AB009866 Bacteriophage phi PVL proviral DNA, complete sequence gil3341907|dbjlAB009866|AB009866 [3341907] (View GenBank report,FASTA report,ASN.1 report,Graphical view,63 protein links, or 1 nucleotide neighbor) Z47794 Bacteriophage Cp-1 DNA, complete genome gil2288892lembIZ477941BPCPIXX [2288892] (View GenBank report,FASTA report,ASN.1 report,Graphical view,3 MEDLINT links, 28 protein links, I nucleotide neighbor, or I genome link) SEGCP7RSIT Bacteriophage Cp-7 (S.pneumoniae) 5 inverted terminal repeat gil 166186|gbIlSEG CP7RSIT [166186] (View GenBank report,FASTA report,ASN.1 report,Graphical view, or 1 MEDLINE link) M11635 Bacteriophage Cp-7 (S.pneumoniae) DNA, 3' inverted terminal repeat gil166185|gblM I6351CP7RSIT2 [166185] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) M11636 Bacteriophage Cp-7 (S.pneumoniae) 5' inverted terminal repeat gil 166184|gb|M 11636ICP7RSITI (166184] (View GenBank report,FASTA reportASN.1 report, or Graphical view) SEGCPSRSIT Bacteriophage Cp-5 (S.pneumoniae), 5' inverted terminal repeat gil l6618llgblSEGCP5RSIT (166181] (View GenBank report,FASTA report,ASN. I report,Graphical view, or 1 MEDLINE link) M11633 Bacteriophage Cp-5 (S.pneumoniae) 3' inverted terminal repeat gill6618OlgbjMll6331CPSRSIT2 [166180] (View GenBank report,FASTA report,ASN. 1 report, or Graphical view) Ml 1634 Bacteriophage Cp-5 (S.pneumoniae), 5' inverted terminal-repeat gill661791gblM116341CPSRSITI (166179] (View GenBank report,FASTA reportASN.1 report, or Graphical view) M34780 Bacteriophage Cp-9 muramidase (cpl9) gene gil 166187|gbIM34780CP9CPL [166187] (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, 1 protein link, or 1 nucleotide neighbor) M34652 Bacteriophage HB-3 amidase (hbl) gene, complete cds gil215O55|gbjM34652jHB3HBLA (215055] (View GenBank report,FASTA report,ASN.I reportGraphical view,I MEDLINE link, or 1 protein link) U64984 Streptococcus pyogenes phage T12 repressor, excisionase (xis), integrase(int) and crythrogenic toxin A precursor (speA) genes, complete cds gill877426|gbIU40453SPU40453 (1877426] (View GenBank reportFASTA reportASN. 1 reportGraphical view,2 MEDLINE links, 4 protein links, or 22 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 245 X12375 Phage CP-Tl (Vibrio cholerae) DNA for packaging signal (pac site) gil15435lemblX12375INCCPPAC [15435] (View GenBank report,FASTA report,ASN.I report,Graphical view,I MEDLINE link, or 1 protein link) AF087814 Vibrio cholerae filamentous bacteriophage fs-2 DNA, complete genome sequence gil3702207IdbjIAB0026321AB002632 [3702207] (View GenBank report,FASTA report,ASN. I report,Graphical view, 1 MEDLIE link, 9 protein links, or 1 genome link) D83518 Bacteriophage KVP40 gene for major capsid protein precursor, complete cds gil3046858ldbjID83518ID83518 [3046858] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I MEDLINE link, or 1 protein link) AF033322 Bacteriophage PST single-stranded binding protein (gene 32) gene, partial cds, and 5' region gil2645774igblAF0333221AF033322 [2645774] (View GenBank report,FASTA report,ASN.1 report,Graphical view,I protein link, or 17 nucleotide neighbors) X94331 Bacteriophage L cro, 24, c2, and cl genes gil 1469213|embIX9433 1 IBLCRO24C [1469213] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, or 4 protein links) U82619 Shigella flexneri bacteriophage V glucosyl transferase (gtr), integrase (int) and excisionase (xis) genes, complete cds gi!2465470igblU82619ISFU82619 [2465470] (View GenBank reportFASTA report,ASN.I reportGraphical view,I MEDLINE link, 8 protein links, or I nucleotide neighbor) WO 00/32825 PCT/I1399/02040 246 Table 12 NCBI Entrez Nucleotide QUERY Key words: bacteriophage and lysis 56 citations found (all selected) AJO 11581 Bacteriophage PSI 19 lysis genes 13, 19, 15, and packaging gene 3, complete cds gil36760841emblAJ0115811BPS011581 [3676084] (View GenBank report,FASTA reportASN.1 report,Graphical view,4 protein links, or I nucleotide neighbor) AJOI 1580 Bacteriophage PS34 lysis genes 13, 19, 15, antiterminator gene 23, and packaging gene 3, complete cds gil36760781emblAJO1 1580BPSO1 1580 (3676078] (View GenBank report,FASTA report,ASN. 1 reportGraphical view,5 protein links, or 2 nucleotide neighbors) AJOI 1579 Bacteriophage PS3 lysis genes 13, 19, 15, and packaging gene 3 gil36760731emblAJ01 15791BPS01 1579 [3676073] (View GenBank report,FASTA reportASN.1 report,Graphical view,4 protein links, or I nucleotide neighbor) AF034975 Bacteriophage H-19B essential recombination function protein (erf), kil protein (kil), regulatory protein cII (cII), protein gp17 (17), N protein (N), ci protein (cI), cro protein (cro), cII protein (cHI), 0 protein (0), P protein (P), ren protein (ren), Roi (roi), Q protein (Q), Shiga-like toxin A (sit-IA) and B (slt-rB) subunits, and putative holin protein (S) genes, complete cds gil26687511gblAF0349751 [2668751] (View GenBank reportFASTA report,ASN.1 reportGraphical view,1 MEDLINE link, 20 protein links, or 30 nucleotide neighbors) U37314 Bacateriophage lambda Rz1 protein precursor (Rzl) gene, complete cds gil10177801gblU373141BLU37314 [1017780] (View GenBank report,FASTA reportASN.1 reportGraphical view,2 MEDLINE links, I protein link, or 9 nucleotide neighbors) U00005 E. coli hflA locus encoding the hf[X, hflK and hfIC genes, hfq gene, complete cds; miaA gene, partial cds gid4361531gbUolU0005ECOHFLA [4361531 (View GenBank reportFASTA reportASN.1 report,Graphical view,4 MEDLINE WO 00/32825 PCT/IB99/02040 247 links, 5 protein links, or 8 nucleotide neighbors U32222 Bacteriophage 186, complete sequence gi]33372491gbIU322221BIU32222 [3337249] (View GenBank report,FASTA reportASN. I report,Graphical view,6 MEDLINE links, 46 protein links, or 5 nucleotide neighbors) AF064539 Bacteriophage N15, complete genome gi131926831gblAF064539iAF064539 [31926831 (View GenBank report,FASTA reportASN.I report,Graphical view,2 MEDLINE links, 60 protein links, 26 nucleotide neighbors, or 1 genome link) AF063097 Bacteriophage P2, complete genome gil31390861gblAF0630971AF063097 (3139086] (View GenBank report,FASTA reportASN.1 report,Graphical view,21 MEDLINE links, 42 protein links, 3 nucleotide neighbors, or 1 genome link) Z97974 Bacteriophage phiadh lys, hol, intG, rad,and tec genes gi!2707950lembiZ97974JBPHIADH (2707950] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 9 protein links, or 1 nucleotide neighbor) AF059243 Bacteriophage NL95, complete genome gil3088545gblAF0592431AF059243 [3088545] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 4 protein links, 3 nucleotide neighbors, or 1 genome link) AF052431 Bacteriophage MI I A-protein, coat protein, Al-protein, and replicas genes, complete cds gil29812081gblAF0524311 [2981208] (View GenBank reportFASTA report,ASN.1 reportGraphical view,2 MEDLINE links, 4 protein links, or 8 nucleotide neighbors) Y07739 Staphylococcus phage Twort holTW, plyTW genes gil2764979lemblY7739BPTWGHOLG [27649791 (View GenBank report,FASTA reportASN.1 report,Graphical view, or 2 protein links) X94331 WO 00/32825 PCT/IB99/02040 248 Bacteriophage L cro, 24, c2, and cl genes gil14692131emblX943311BLCRO24C [1469213] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 4 protein links) X78410 Bacteriophage phiadh holin and lysin genes gil7938481embIX78410ILGHOLLYS [793848] (View GenBank report,FASTA reportASN.1 report,GraphicaLview,1 MEDLINE link, 2 protein links, or I nucleotide neighbor) X99260 Bacteriophage B 103 genomic sequence gil 14292291emblX992601BB103G [1429229] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 17 protein links, or 12 nucleotide neighbors) AJ000741 Bacteriophage P1 darA operon gil2462938lemblAJ0007411BPAJ7641 [2462938] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 10 protein links, or 31 nucleotide neighbors) X87420 Bacteriophage ES18 genes 24, c2, cro, ci, 18, and oL and oR operators gill 1434071emb1X874201BPES 18GEN [1143407] (View GenBank reportFASTA reportASN.1 report,Graphical view,5 protein links, or 9 nucleotide neighbors) L35561 Bacteriophage phi-105 ORFs 1-3 gil5322181gblL355611PH5ORFHTR [532218] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 3 protein links) D10027 Group II RNA coliphage GA genome gil2l7784ldbjlD100271PGAXX [217784] (View GenBank reportFASTA reportASN.1 reportGraphical view,1 MEDLINE link, 3 protein links, 5 nucleotide neighbors, or 1 genome link) V01 128 Bacteriophage phi-X174 (cs7O mutation) complete genome gil 15535lemblVO 1281PHIX174 [15535] (View GenBank reportFASTA reportASN.1 reportGraphical view,4 MEDLINE links, 11 protein links, or 26 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 249 S81763 coat gene...replicase gene [bacteriophage KUI, host=Escherichia coli, group H RNA phage, Genomic RNA, 3 genes, 120 nt] gil14387661gblS81763lS81763 [1438766] (View GenBank report,FASTA reportASN.1 report,Graphical view, or 1 MEDLINE link) U38906 Bacteriophage rlt integrase, repressor protein (rro), dUTPase, lIolin and lysin genes, complete cds gil 13535171gblU389061BRU38906 [13535171 (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 50 protein links, or 3 nucleotide neighbors) X91149 Bacteriophage phi-C31 DNA cos region gill 107473lemblX911491APHIC31C [1107473] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 6 protein links, or 1 nucleotide neighbor) V00642 phage MS2 genome gili50811embIV00642ILEMS2X [15081] (View GenBank report,FASTA reportASN. 1 report,Graphical view,8 MEDLINE links, 4 protein links, or 20 nucleotide neighbors) VO 1146 Genome of bacteriophage T7 gil431187lemblVOl 1461T7CG [431187] (View GenBank reportFASTA reportASN.1 report,Graphical view,13 MEDLINE links, 60 protein links, 105 nucleotide neighbors, or 1 genome link) X78401 Bacteriophage P22 right operon, orf 48, replication genes 18 and 12, nin region genes, ninG phosphatase, late control gene 23, orf 60, complete. cds, late control region, start of lysis gene 13 gil5l2343lemblX784011POP22NIN [5123431 (View GenBank reportFASTA report.ASN. 1 repor,Graphical view,2 MEDLINE links, 13 protein links, or 4 nucleotide neighbors) Y00408 Bacteriophage T4 gene t for lysis protein gil 15368lemblYO04081MYT4T [15368] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors) Z26590 WO 00/32825 PCT/IB99/02040 250 Bacteriophage mv4 lysA and lysB genes gil4105001embIZ265901MV4LYSAB [410500] (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 4 protein links) X07809 Phage phiX 174 lysis (E) gene upstream region gil 15094lemblX078091MIPHIXE [15094] (View GenBank report,FASTA reportASN.I report,Graphical view,1 MEDLINE link, 2 protein links, or 4 nucleotide neighbors) Z34528 Lactococcal bacteriophage c2 lysin gene giI5O64551embIZ34528LBC2LYSIN [506455] (View GenBank report,FASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors) X15031 Bacteriophage fr RNA genome giIl507I1embXl503l1LEBFRX [15071] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 4 protein links, 9 nucleotide neighbors, or I genome link) X80191 Bacteriophage PP7 mRNA for maturation, coat, lysis and replicase proteins gil517237IemblX8019l1BPP7PR [517237] (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, 4 protein links, or 1 genome link) X85010 Bacteriophage A511 plySl1 gene gil853748lemblX850101BPA511PLY [853748] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or I nucleotide neighbor) X85009 Bacteriophage A500 hol5O and ply5O0 genes gil8537441embIX850091BPA500PLY [853744] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 3 protein links, or 4 nucleotide neighbors) X85008 Bacteriophage Al18 holl 18 and ply11 8 genes gil853740lemblX85008lBPA I 18PLY [853740] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or I nucleotide neighbor) WO 00/32825 PCT/IB99/02040 Z35638 251 Bacteriophage phi-X174 genes for lysis protein and beta-lactamase gil520996IembIZ35638IBPLYSPR [520996] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 516 nucleotide neighbors) J02459 Bacteriophage lambda, complete genome giil2151O4IgbIJO24591LAMCG [215104] (View GenBank report,FASTA report,ASN.1 report,Graphical view,87 MEDLINE links, 67 protein links, 190 nucleotide neighbors, or 1 genome link) X87674 Bacteriophage P1 lydA & lydB genes gil974763lemblX876741BACP1LYD [974763] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) X87673 Bacteriophage P1 gene 17 gil974761lembX876731BACP117 [974761] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 1 protein link, or I nucleotide neighbor) M14784 Bacteriophage T3 strain amNG220B right end, tail fiber protein, lysis protein and DNA packaging proteins, complete cds gil21581lgblMI4784IPT3RE [2158101 (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 9 protein links, or 10 nucleotide neighbors) M11813 Bacteriophage PZA (from B.subtilis), complete genome gil2l6O461gblM1 18131PZACG [216046] (View GenBank report,FASTA reportASN.1 report,Graphical view,3 MEDLINE links, 27 protein links, 17 nucleotide neighbors, or 1 genome link) M16812 Bacteriophage K3 't' lysis gene, complete cds gil2155031gblM168121PK3LYST [215503] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 4 nucleotide neighbors) J04356 Bacteriophage P22 proteins 15 (complete cds), and 19 (3' end) genes gil215265lgblJ04356P2215P [215265] WO 00/32825 PCT/IB99/02040 252 (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or 2 nucleotide neighbors) J04343 Bacteriophage JP34 coat and lysis protein genes, complete cds, and replicase protein gene, 5' end gi12150761gbIJO4343iJP3COLY [215076] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 3 protein links, or 2 nucleotide neighbors) J02482 Bacteriophage phi-X174, complete genome gil2l6Ol9IgbIJO24821PXICG [216019] (View GenBank report,FASTA reportASN.1 report,Graphical view,23 MEDLINE links, 11 protein links, 26 nucleotide neighbors, or 1 genome link) M99441 Bacteriophage T4 and-sigma 70 protein (asiA) gene, complete cds and lysis protein, 3' end gil21582OlgblM994411PT4ASIA [215820] (View GenBank report,FASTA reportASN.1 report,Graphical view,3 MEDLINE links, 2 protein links, or 2 nucleotide neighbors) M65239 Bacteriophage 21 lysis genes S. R, and Rz, complete eds gil215466gblM652391PH2LYSGEN [215466] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 3 protein links, or 1 nucleotide neighbor) M10637 Phage G4 D/E overlapping gene system, encoding D (morphogenetic) and E (lysis) proteins gil2154271gbM10637PG4DE [215427] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 12 nucleotide neighbors) J02454 Bacteriophage G4, complete genome gil215415lgblJ024541PG4CG [2154151 (View GenBank reportFASTA report,ASN. 1 report,Graphical view,6 MEDLINE links, I1 protein links, 20 nucleotide neighbors, or 1 genome link) J02580 Bacteriophage PA-2 (E.coli porcine strain isolate) Rz gene, 5'end; ORF2, outer membrane porin protein (c) and ORF1 genes, complete cds gil2153661gblJ02580lPA2LC [215366] (View GenBank reportFASTA reportASN. 1 reportGraphical view, 1 MEDLINE link, 4 protein links, or 4 nucleotide neighbors) WO 00/32825 PCT/I1399/02040 253 M 14782 Bacillus phage phi-29 head morphogenesis, major head protein, head fiber protein, tail protein, upper collar protein, lower collar protein, pre-neck appendage protein, morphogenesis(13), lysis, morphogenesis(15), encapsidation genes, complete cds giL2153231gblM14782|P29LATE2 [215323] (View GenBank report,FASTA reportASN.1 report,Graphical view,I MEDLINE link, 11 protein links, or 11 nucleotide neighbors M10997 Bacteriophage P22 lysis genes 13 and 19, complete cds gil215262igblM109971P221319 [215262] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 3 nucleotide neighbors) J02467 Bacteriophage MS2, complete genome gi1215232lgbIJ024671MS2CG [215232] (View GenBank report,FASTA reportASN.1 report,Graphical view,8 MEDLINE links, 4 protein links, 20 nucleotide neighbors, or I genome link) M14035 Bacteriophage lambda lysis S gene with mutations leading to nonlethality of S in the plasmid pRG1 gil21518OgblMl4035lLAMLYS [215180] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 14 nucleotide neighbors) U04309 Bacteriophage phi-LC3 putative holin (lysA) gene and putative murein hydrolase (lysB) gene, complete cds gil530796IgblUO43091BPU04309 [530796] (View GenBank report,FASTA reportASN.1 reportGraphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 254 Table 13 NCBI Entrez Nucleotide QUERY Key word: holin 51 citations found (all selected) AF034975 Bacteriophage H-19B essential recombination function protein (erf), kil protein (kil), regulatory protein cIII (cIII), protein gp17 (17), N protein (N), cI protein (ci), cro protein (cro), clI protein (cII), 0 protein (0), P protein (P), ren protein (ren), Roi (roi), Q protein (Q), Shiga-like toxin A (sit-IA) and B (sit-IB) subunits, and putative holin protein (S) genes, complete cds gil2668751igblAF0349751 [2668751] (View GenBank report,FASTA reportASN. 1 report,Graphical view,1 MEDLINE link, 20 protein links, or 30 nucleotide neighbors) U52961 Staphylococcus aureus holin-like protein LrgA (IrgA) and LrgB (IrgB) genes, complete cds gil1841516igblU529611SAU52961 [1841516] (View GenBank report,FASTA reportASN.1 report,Graphical view, I MEDLINE link, 2 protein links, or I nucleotide neighbor) U28154 Haemophilus somnus cryptic prophage genes, capsid scaffolding protein gene, partial cds, major capsid protein precursor, endonuclease, capsid completion protein, tail synthesis proteins, holin, and lysozyme genes, complete cds gil1765928igblU281541HSU28154 [1765928] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 13 protein links) AF032122 Streptococcus thermophilus bacteriophage Sfi19 central region of genome gil29356821gblAF0321221 [2935682] (View GenBank report,FASTA reportASN.1 report,Graphical view,l MEDLINE link, 14 protein links, or 2 nucleotide neighbors) AF032121 Streptococcus thermophilus bacteriophage Sfi2l central region of genome gil2935667igblAF032121LAF032121 [2935667] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINEL link, 14 protein links, or 2 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 255 AF021803 Bacillus subtilis 168 prophage SPbeta N-acetylmuramoyl-L-alanine amidase (blyA), holin-like protein (bhlA), holin-like protein (bhiB), and yolK genes, complete cds; and yolJ gene, partial cds gi12997594gblAF0218031AF021803 [2997594] (View GenBank report,FASTA reportASN.I report,Graphical view,1 MEDLINE link, 5 protein links, or 1 nucleotide neighbor) AF057033 Streptococcus thermophilus bacteriophage sfill gp502 (orf502), gp284 (orf284), gp129 (orfl29), gp193 (orfl93), gpl19 (orf l19), gp348 (orf348), gp53 (orf53), gpl 13 (orf 113), gpl4 (orf 104), gp 114 (orfl 14), gp128 (orfl28), gpl68 (orf 168), gpl 17 (orf117), gp105 (orf 105), putative minor tail protein (orfl510), putative minor structural protein (orf512), putative minor structural protein (orf1000), gp373 (orf373), gp57 (orf57), putative anti-receptor (orf695), putative minor structural protein (orf669), gp149 (orf 149), putative holin (orf 141), putative holin (orf87), and lysin (orf288) genes, complete cds gil3320432lgblAF057033LAF057033 [3320432] (View GenBank report,FASTA reportASN. 1 report,Graphical view,25 protein links, or 1 nucleotide neighbor) U32222 Bacteriophage 186, complete sequence gil33372491gblU322221B1U32222 [3337249] (View GenBank report,FASTA reportASN.1 report,Graphical view,6 MEDLINE links, 46 protein links, or 5 nucleotide neighbors) AB009866 Bacteriophage phi PVL proviral DNA, complete sequence gil3341907ldbjlAB0098661AB009866 [3341907] (View GenBank reportFASTA reportASN.1 report,Graphical view,63 protein links, or 1 nucleotide neighbor) AF009630 Bacteriophage bIL170, complete genome gil3282260lgblAF0096301AF009630 [3282260] (View GenBank report,FASTA reportASN. 1 report,Graphical view,63 protein links, 3 nucleotide neighbors, or 1 genome link) AF064539 Bacteriophage N15, complete genome WO 00/32825 PCT/IB99/02040 256 gil31926831gblAF0645391AF064539 [3192683] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 60 protein links, 26 nucleotide neighbors, or I genome link) AF063097 Bacteriophage P2, complete genome gil3139086|gblAF0630971AF063097 [3139086] (View GenBank report,FASTA reportASN.1 report,Graphical view,21 MEDLINE links, 42 protein links, 3 nucleotide neighbors, or 1 genome link) Z97974 Bacteriophage phiadh lys, hol, intG, rad,and tec genes gil 27 07950iembIZ97974lBPHIADH [2707950] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 9 protein links, or 1 nucleotide neighbor) X95646 Streptococcus thermophilus bacteriophage Sfi21 DNA; lysogeny module, 8141 bp gi 1 22927471emblX95646BSFI2 ILYS [2292747] (View GenBank report,FASTA report,ASN.1 report,Graphical view,2 MEDLINE links, 19 protein links, or 3 nucleotide neighbors) SEGLLHLYSINO Bacteriophage LL-H structural protein gene, partial cds; minor structural protein gp6l (g57), unknown protein, unknown protein, structural protein (g20), unknown protein, unknown protein, major capsid protein (g34), main tail protein gp19 (gl7), holin (hol), muramidase (mur), unknown protein, unknown protein, unknown protein, unknown protein, unknown protein, and unknown protein genes, complete cds; unknown protein gene, partial cds; and unknown protein, unknown protein, unknown protein, unknown protein, unknown protein, minor structural protein gp75 (g70), minor structural protein gp89 (g88), minor structural protein gp58 (g71), unknown protein, unknown protein, unknown protein, and unknown protein genes, complete cds gil 1004337IgbiSEG_LLHLYSINO [1004337] (View GenBank report,FASTA reportASN.1 report,Graphical view,4 MEDLINE links, 31 protein links, or 1 nucleotide neighbor) M96254 Bacteriophage LL-H holin (hol), muramidase (mur), and unknown protein genes, complete cds gil10O43361gblM96254LLLHLYSINO3 [1004336] (View GenBank report,FASTA reportASN.1 report, or Graphical view) WO 00/32825 PCT/IB99/02040 257 Y07740 Staphylococcus phage 187 ply187 and hollS7 genes gil27649821emblYO77401BP187PLYH (2764982] (View GenBank report,FASTA reportASN.1 report,Graphical view, or 2 protein links ) U88974 Streptococcus thermophilus bacteriophage 01205 DNA sequence gi124440801g blU88974 [2444080) (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 57 protein links, or 6 nucleotide neighbors) Z99117 Bacillus subtilis complete genome (section 14 of 21): from 2599451 to 2812870 gil2634966lembiZ99117IBSUB0014 [2634966] (View GenBank report,FASTA reportASN.1 report,Graphical view,233 protein links, 51 nucleotide neighbors, or 1 genome link) Z99115 Bacillus subtilis complete genome (section 12 of 21): from 2195541 to 2409220 gil2634478emblZ99115JBSUB0012 [2634478] (View GenBank report,FASTA reportASN.1 report,Graphical view,244 protein links, 64 nucleotide neighbors, or I genome link) Z99110 Bacillus subtilis complete genome (section 7 of 21): from 1194391 to 1411140 gil26334721emblZ991 1OIBSUB0007 [2633472] (View GenBank report,FASTA reportASN.1 report,Graphical view,226 protein links, 31 nucleotide neighbors, or 1 genome link) X78410 Bacteriophage phiadh holin and lysin genes gil793848lembX78410ILGHOLLYS [793848] (View GenBank reportFASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) Z93946 WO 00/32825 PCT/IB99/02040 258 Bacteriophage Dp-1 dph and pal genes and 5 open reading frames gil 19347601emblZ93946|BPDP1ORFS [1934760] (View GenBank report,FASTA reportASN.1 report,Graphical view, or 6 protein links) AF011378 Bacteriophage skl complete genome gi12392824lgblAF01 13781AF01 1378 [2392824] (View GenBank report,FASTA report,ASN. 1 report,Graphical view,54 protein links, 2 nucleotide neighbors, or 1 genome link) Z47794 Bacteriophage Cp-1 DNA, complete genome gil2288892lemblZ47794lBPCP1XX [2288892] (View GenBank report,FASTA reportASN.1 report,Graphical view,3 MEDLINE links, 28 protein links, 1 nucleotide neighbor, or 1 genome link) L35561 Bacteriophage phi-105 ORFs 1-3 gil5322181gbIL35561IPH50RFHTR [532218] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, or 3 protein links) D49712 Bacillus licheniformis DNA for ORFs, xpaL2 homologous protein and xpaLl homologous protein, complete and partial cds gil1514423ldbjlD49712lD49712 [1514423] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, or 4 protein links) X90511 Lactobacillus bacteriophage phigle DNA for Rorf 162, Holin, Lysin, and Rorf 175 genes gil 1926386lemblX9051 1ILBPHIHOL [1926386] (View GenBank reportFASTA reportASN.1 report,Graphical view,4 protein links, or 1 nucleotide neighbor) X98106 Lactobacillus bacteriophage phigle complete genomic DNA gill926320lemblX981061LBPHIG1E [1926320] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE WO 00/32825 PCT/IB99/02040 259 link, 50 protein links, or 4 nucleotide neighbors) U72397 Bacteriophage 80 alpha holin and amidase genes, complete cds gil17632411gblU723971BSU72397 [1763241] (View GenBank report,FASTA reportASN. 1 report,Graphical view,2 protein links, or 2 nucleotide neighbors) U38906 Bacteriophage rlt integrase, repressor protein (rro), dUTPase, holin and lysin genes, complete cds gil13535171gbIU389061BRU38906 [1353517] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 50 protein links, or 3 nucleotide neighbors) X91149 Bacteriophage phi-C31 DNA cos region gill 107473lemblX911491APHIC31C [1107473] (View GenBank report,FASTA reportASN. 1 report,Graphical view, 1 MEDLINE link, 6 protein links, or 1 nucleotide neighbor) U24159 Bacteriophage HP1 strain HP1c1, complete genome gil1O462351gblU241591BHU24159 [1046235] (View GenBank report,FASTA reportASN.1 report,Graphical view,6 MEDLINE links, 41 protein links, 8 nucleotide neighbors, or 1 genome link) Z26590 Bacteriophage mv4 lysA and lysB genes gil41O500lernbIZ265901MV4LYSAB [410500] (View GenBank report,FASTA reportASN. 1 report,Graphical view, or 4 protein links) Z70177 B.subtilis DNA (28 kb PBSX/skin element region) gill225934lembIZ70177[BSPBSXSE [1225934] (View GenBank reportFASTA reportASN.1 report,Graphical view,32 protein links, or 4 nucleotide neighbors) Z36941 WO 00/32825 PCT/IB99/02040 260 B.subtilis defective prophage PBSX xhlA, xhlB, and xylA genes gil535793embIZ36941IBSPBSXXHL [5357931 (View GenBank report,FASTA reportASN. I report,Graphical view,4 protein links, or 5 nucleotide neighbors) X89234 L.innocua DNA for phagelysin and holin gene gil 11348441 embIX892341LICPLYHOL [1134844] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 4 nucleotide neighbors) X85010 Bacteriophage A51I1 ply 5 1 1 gene gil8537481emblX850101BPA511PLY [853748] (View GenBank report,FASTA reportASN. 1 report,Graphical view,1 MEDLINE link, 3 protein links, or 1 nucleotide neighbor) X85009 Bacteriophage A500 hol500 and ply5OO genes gil8537441embX850091BPA500PLY [853744] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or 4 nucleotide neighbors) X85008 Bacteriophage A118 hol118 and ply118 genes gil853740lembiX850081BPAl 18PLY [853740] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or 1 nucleotide neighbor) L34781 Bacteriophage phi 11 holin homologue (ORF3) gene, complete cds and peptidoglycan hydrolase (lytA) gene, partial cds gil5118381gblL347811BPHHOLIN [511838] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 4 protein links, or 2 nucleotide neighbors) U11698 Serratia marcescens SM6 extracellular secretory protein (nucE), putative phage lysozyme (nucD), and transcriptional activator (nucC) genes, complete cds giI509550lgblUl 16981SMU1 1698 [509550) (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE WO 00/32825 PCT/IB99/02040 261 link, 3 protein links, or 1 nucleotide neighbor) U31763 Serratia marcescens phage-holin analog protein (regA), putative phage lysozyme (regB), and transcriptional activator (regC) genes, complete cds gil9650681gblU31763[SMU31763 [965068] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 3 protein links, or I nucleotide neighbor) X87674 Bacteriophage P1 lydA & lydB genes gil 9 7 4763lembIX876741BACP1LYD [974763] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 2 nucleotide neighbors) L48605 Bacteriophage c2 complete genome gil 1 462761gbIL486051C2PVCG [1146276] (View GenBank report,FASTA reportASN. 1 report,Graphical view,3 MEDLINE links, 39 protein links, 3 nucleotide neighbors, or 1 genome link) L33769 Bacteriophage bIL67 DNA polymerase subunit (ORF3-5), essential recombination protein (ORF13), lysin (ORF24), minor tail protein (ORF3 1), terminase subunit (ORF32), holin (ORF37), unknown protein (ORF 1-2,6-12,14-23,25-30,33-36), complete genome gil5222521gblL33769L67CG [522252] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 37 protein links, 2 nucleotide neighbors, or 1 genome link) L31348 Bacteriophage Tuc2009 integrase (int) gene, complete cds; lysin (lys) gene, 3' end gil508612IgblI.12348JTU2INT [508612] (View GenBank reportFASTA reportASN.1 report,Graphical view,2 MEDLINE links, 3 protein links, or 3 nucleotide neighbors) L31364 Bacteriophage Tuc2009 holin (S) gene, complete cds; lysin (lys) gene, complete cds gil4962811gblL313641TU2SLYS [496281] WO 00/32825 PCT/IB99/02040 262 (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) L31366 Bacteriophage Tuc2009 structural protein (mp2) gene, complete cds gi4962781gblL313661TU2MP2A [496278] (View GenBank report,FASTA reportASN.1 repor,Graphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) 131365 Bacteriophage Tuc2009 structural protein (mpI) gene, complete cds gil496276gbIL313651TU2MP1A [4962761 (View GenBank report,FASTA reportASN.I report,Graphical view,1 MEDLINE link, or 1 protein link) U04309 Bacteriophage phi-LC3 putative holin (lysA) gene and putative murein hydrolase (lysB) gene, complete cds gil5307961gblU043091BPUo4309 [5307%] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 2 protein links, or 1 nucleotide neighbor) WO 00/32825 PCT/IB99/02040 263 Table 14 NCBI Entrez Nucleotide QUERY Key word: bacteriophage and kil 5 citations found (all selected) AF034975 Bacteriophage H-19B essential recombination function protein (erf), kil protein (kil), regulatory protein cIII (cIII), protein gp17 (17), N protein (N), cl protein (ci), cro protein (cro), clI protein (cli), 0 protein (0), P protein (P), ren protein (ren), Roi (roi), Q protein (Q), Shiga-like toxin A (sit-IA) and B (slt-IB) subunits, and putative holin protein (S) genes, complete cds gil26687511lgblAF0349751 [2668751] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 20 protein links, or 30 nucleotide neighbors) X15637 Bacteriophage P22 P(L) operon encompassing ral, 17, kil and arf genes gil15646lemblX156371POP22PL [15646] (View GenBank report,FASTA reportASN.I report,Graphical view,I MEDLINE link, 7 protein links, or 2 nucleotide neighbors) J02459 Bacteriophage lambda, complete genome gil2151041gbIJ02459lLAMCG [215104] (View GenBank reportFASTA reportASN.1 report,Graphical view,87 MEDLINE links, 67 protein links, 190 nucleotide neighbors, or 1 genome link) M64097 Bacteriophage Mu left end gil215543gbIM640971MULEFTEN [215543] (View GenBank report,FASTA reportASN.1 report,Graphical view,2 MEDLINE links, 39 protein links, or 15 nucleotide neighbors) M18902 Bacteriophage D108 kil gene encoding a replication protein, 3' end; and containing three ORFs, complete cds gil1661911gblM18902ID18KIL [166191] (View GenBank report,FASTA reportASN.1 report,Graphical view,1 MEDLINE link, 1 protein link, or 3 nucleotide neighbors) WO 00/32825 PCT/IB99/02040 264 Table 15 U77328 V01282 U11787 U93688 A47599 D21131 U76864 U38428 AF151117 AF121672 U11786 U93687 A47598 D30690 U76863 U66665 AF1 E1218 AF072726 U11785 AJ224764 A47597 D14711 U76862 U66664 AF146368 AF115379 U11784 AF064774 A47596 D90119 U76861 U66663 AF144661 AF034153 U11783 AF064773 A47595 D00730 U76860 X87104 AF132117 AF029244 U11782 Y14370 A47594 D83357 U76859 X87105 Y15477 U67965 U11781 AF065394 A44534 D83356 U76858 X89233 Y09928 U96610 U11780 AF062376 A44533 D83355 U76857 M28521 Y09594 U96609 U11779 AF062375 A44529 D83354 U76855 U54636 AF134905 U73027 U11778 AF062374 A44528 D83353 U76854 U46541 AB019536 U73026 U11777 AF062373 A44527 D12572 U76853 L14017 AJ237696 U73025 U11776 AB007500 A44526 D86727 U76852 U60589 AF106851 AF068904 U11775 Y09924 A44525 D86240 U76851 X48003 AF106850 U60050 U11774 U63529 A39696 D67075 U76850 M37889 AF106849 D10907 U11773 AF033191 AF001783 D67074 U76849 V01281 M26321 D10906 AF053772 Y15856 AF001782 U97062 U76848 X97985 AF060191 AF053140 AF053771 AB000439 L77194 U96620 U76847 X00127 AF060190 AB013298 AF029731 AF041467 AF003593 U96619 Y09929 X03286 AF060189 Y16431 AF027155 Y14051 AF003592 Z84573 Y09570 X62282 AF060188 AF076684 AF024571 U82085 X73889 AB0I1896 X95848 X01645 AF060187 AF076683 U87144 AF026122 X74219 Y07645 Y09428 X16471 AF060186 Y13225 AF086644 AF026121 Y10419 U92441 S76611 X52734 AF060185 AF094826 AJ223781 AF026120 M63177 U91741 S76213 X13290 AF060184 AJ223480 AF076030 AB009635 E08773 U29454 S75707 X66088 AF036324 AF093548 AF044951 AB006796 E07163 U29478 575706 Z30588 AF036323 AJ005352 AF044906 U39769 E07162 U77374 575705 X16457 AF053568 AF051916 AF044905 D00184 E07161 L42945 S76270 X00342 AJ132841 Y09927 AF044904 X56628 E07160 U38429 572497 V01287 Y13766 AF051917 AF044903 AF033018 E07159 U81980 572488 X61307 AF101234 S77058 AF044902 AF034076 E07158 X55185 574031 Y00356 AJ133520 S65052 AF044901 D82063 E07157 V01278 567449 X06603 AJ133495 AF009671 AF044900 D76414 E07156 U31979 U75367 Z93205 AJ132803 U81973 AF044899 U57060 E07155 X91786 U75368 X64172 AB016487 U77308 AF044898 D89066 E03836 U36912 U31175 X72700 ABI16431 U20869 AF044897 U85095 E03835 U36911 X53096 X60827 AB015981 U89396 AF044075 U85097 E03526 U36910 X53951 X64389 AB015195 U94706 AF044074 U85096 E02873 U64885 X53952 X62288 AF107307 U41072 AF044073 D42078 E01690 U76872 X03408 X55798 AF079518 U52961 AF044072 AF015929 E00876 U76871 U50629 X58434 AJ223806 U21636 AF044071 D10369 E00203 U76870 U38656 X06627 Y18018 U65000 AF044070 A48955 D83951 U76869 U58139 X12831 Y17795 U48826 AF044069 A48501 D17366 U76868 A31894 X07371 AJ005647 U20503 AF044068 A48500 D42144 U76867 L42943 X02529 AJ005646 U11789 AF044067 A48499 D42143 U76866 U51474 _ Y00688 AJ005645 U11788 AF044066 A47600 D10489 U76865 U50077 -X04121 X59477 X54338 A12915 U51133 M63176 M10500 L01055 M63917 X59478 X51661 A12913 U51132 L11998 M10499 M83994 M58515 X63598 X05815 A12906 X02588 L05004 AH000934 J03947 10909 X52593 X15574 A12905 X61716 L42764 M10498 J03479 M15067 WO 00/32825 PCT/I B99102040 265 X76490 Y07536 A12904 X61719 M32103 M10497 IM64724 M92376 X81586 X02166 A12903 X61718 U10927 M18264 M14372 M62650 X72014 Z49245 A12902 X67743 AH003057 J01786 M14371 M32312 X72013 X16298 A12901 X67742 M73535 M33833 M14374 M20393 X71437 Z18852 A12900 X67741 M73536 M32470 M15215 M90536 X62992 X68417 A12899 X67740 U20782 M20270 M36694 M21854 X52594 X68425 A12898 X67738 L37598 J03323 M37915 M36771 X14827 X17679 A12897 U02910 L37597 M33479 M12715 L14020 X13404 X63072 A12896 AH003349 L36472 M94061 J04151 M81736 X17301 X02872 A09523 M1 1118 L25288 M37888 L22566 U1 1702 X17688 V01277 A04518 M18086 L25893 M76714 L13379 L19300 X03097 X52543 A04517 U19459 K02687 M17123 L13378 L25372 Z16422 A19943 A04512 U35773 L23109 M97169 L13377 L22565 Z33409 A19942 L41499 U26702 L07778 M81346 L13376 M58516 Z33408 A19941 U19770 U21221 M90056 M90693 L13375 U06462 Z33407 A19940 X53818 U36379 J02615 M25257 L13374 L19298 Z33406 A19939 M20129 U06451 M18970 M25256 M17348 M80252 Z33405 A19938 L43098 U35036 K02985 M25255 M17357 L11530 Z33404 A19937 L43082 U20794 M21136 M25254 M17347 _____ X75439 A19936 X03216 L25426 M10501 M25253 M28364 _____ X62587 A17958 X70648 M86227 AH000935 M25252 M21319 _____ WO 00/32825 PCT/IB99/02040 266 Table 16 Phage 44AHJD complete genome sequence. 16668 nucleotides. 1 tccatttctt tactaaactt aaaaatgctg tgcaacaact taaccaactt atctaaccta ttacatattc 71 atcaaataca aaatttatgt atctattgac ttttattcaa aattatgatt tcaacatata ataaaattaa 141 tttacttatt taaatattct atgatataat tagttataaa atatttggag gtgtataaat gacagaattt 211 gatgaaatcg taaaaccaga cgacaaagaa gaaacttcag aatcaactga agaaaattta gaatcaactg 281 aagaaacttc agaatcaact gaagaatcaa ctgaagaatc aactgaagaa tcaactgaag ataaaacagt 351 agaaacaatc gaagaagaaa atgaaaacaa attagaacct actacaacag atgaagatag ttcgaaattt 421 gaccctgttg tattagaaca acgtattgct tcattagaac aacaagtgac tactttttta tcttcacaaa 491 tgcaacaacc acaacaagta caacaaacac aatcagatgt aacagaatca aacaaagaag ataacgacta 561 ttcagatgaa gaactagttg ataagttaga tttagattag gaggaattta aacatgtatg agggaaacaa 631 catgcgttct atgatgggta catcatatga agattcaaga ttaaataaac gaacagaatt aaatgaaaac 701 atgtcaattg atacaaataa aagtgaagat agttatggtg tacaaattca ttcactttca aaacaatcat 771 ttacaggtga cgttgaggag gaataataaa ttatggcaca acaatctaca aaaaatgaaa ctgcactttt 841 agtagcaaag tcagctaaat cagcgttaca agattttaat catgattatt caaaatcttg gacatttggc 911 gacaaatggg ataattcaaa tacaatgttc gaaacatttg taaataaata tttattccct aagattaatg 981 agactttatt aatcgatatt gcattaggta atcgttttaa ttggttagct aaagagcaag attttattgg 1051 acaatatagt gaagaatacg tgattatgga cacagtacca attaacatgg acttatctaa aaatgaggaa 1121 ttaatgttga aacgtaatta tccacgtatg gcaactaagt tatatggtaa cggaattgtg aagaaacaaa 1191 aattcacatt aaacaacaat gatacacgtt tcaatttcca aacattagca gacgcaacta attacgcttt 1261 aggtgtatac aaaaagaaaa tttctgatat taatgtatta gaagaaaaag aaatgcgtgc aatgttagtt 1331 gattactcat tgaatcaatt atccgaaaca aatgtacgta aagcaacatc aaaagaagat ttagcaagca 1401 aagtttttga agcaatccta aacttacaaa acaacagtgc taaatataat gaagtacatc gtgcatcagg 1471 tggtgcaatt ggacaatata caactgtatc aaaattaaaa gatattgtga ttttaacaac agattcatta 1541 aaatcttatc ttttagatac taagattgca aacacattcc agattgcagg cattgatttc acagatcacg 1611 ttattagttt tgacgactta ggtggcgtgt ttaaagtaac aaaagaattt aagttacaaa accaagattc 1681 aattgacttt ttacgtgcgt atggagatta tcaatcacaa ttaggagata caattccagt tggtgctgta 1751 tttacttatg atgtatctaa acttaaagag tttactggca acgttgaaga aattaaacca aaatcagatt 1821 tatatgcgtt tattttggat attaattcaa ttaaatataa acgttacaca aaaggtatgt taaaaccacc 1891 attccataac cctgaatttg atgaagttac acactggatt cattactatt catttaaagc cattagtcca 1961 ttctttaata aaattttaat tactgaccaa gatgtaaatc caaaaccaga ggaagaatta caagaataaa 2031 aggagcgtaa aatatgaaca acgataaaag aggtttaaac gttgagttat caaaggaaat cagcaaaaga 2101 gttgttgaac atcgcaacag atttaaacgt cttatgttta atcgttattt ggaattttta ccgctactaa 2171 tcaactatac caatcgtgat acggttggta tagattttat tcagttagaa tcagctttaa gacaaaacat 2241 taatgtagtt gttggtgaag ctagaaataa gcaaattatg attcttggtt atgtaaataa cacttacttt 2311 aatcaagcac caaatttttc atcaaacttt aatttccaat ttcaaaaacg attaactaaa gaagatatat 2381 attttattgt acctgactat ttaatacctg atgattgtct acaaattcat aagctatatg ataactgtat 2451 gagtggtaac tttgttgtca tgcaaaataa accaattcaa tataatagtg atatagaaat tatagaacat 2521 tatactgatg aattagcaga agttgcttta tctcgctttt ctttaatcat gcaagcaaaa tttagcaaga 2591 tatttaaatc agaaattaat gacgagtcaa tcaatcaact tgtgtccgaa atatataacg gtgcaccatt 2661 tgttaaaatg tcacctatgt ttaatgcaga tgacgatatc attgatttaa caagtaatag cgtaatccca 2731 gcattaactg aaatgaaacg ggaatatcaa aacaaaatta gtgaattaag taactattta ggcattaatt 2801 cattagccgt tgataaagaa agcggtgttt cagacgaaga ggcaaaaagt aatcgtggat ttaccacatc 2871 aaacagtaat atctatttaa aaggtcgtga accaattacg tttttatcaa agcgttatgg tttagatatt 2941 aaaccgtatt acgatgatga aacaacgtct aaaatatcaa tggtagacac actttttaaa gatgaaagca 3011 gtgatataaa tggctagata cacaatgact ttatacgatt tcattaaatc agaattgatt aaaaaaggtt 3081 tcaatgaatt tgtaaatgat aataaattaa cgttttatga tgatgaattt caattcatgc aaaaaatgct 3151 gaagttcgac aaagacgttt tagctatcgt taatgaaaaa gtatttaaag gtttttcatt gaaagatgaa 3221 ttatcagatt tactttttaa aaaatcattt acgattcatt ttttagatag agaaatcaac agacaaacag 3291 ttgaagcatt tggcatgcaa gtgattactg tatgtattac acatgaggat tatttaaatg tggtttattc 3361 atcaagtgaa gttgaaaaat acttacaatc acaaggcttc acagaacaca atgaagatac aacaagtaac 3431 actgatgaaa catcgaatca aaatgctaca tctttagaca attcaactgg catgactgca aacagaaacg 3501 cttatgtgtc attaccacaa agtgaggtta acattgatgt tgataataca acgttacgat tcgctgataa 3571 taatacgatt gataacggta aaactgtgaa taaatcgagt aacgaaagta atcaaaacgc aaaacgtaat 3641 caaaatcaaa aaggtaatgc aaaaggtaca caattcacta agcagtattt aattgataat attgataaag 3711 cgtacgattt aagaaagaaa attttaaatg aatttgataa aaaatgtttt ttacaaattt ggtagaggtg 3781 gttaaataat ggcatataat gaaaacgatt ttaaatattt tgatgacatt cgtccatttt tagacgaaat 3851 ttataaaacg agagaacgtt atacaccgtt ttacgatgat agagcagatt ataatactaa ttcaaaatca 3921 tattatgatt atatttcaag attatcaaaa ctaattgaag tattagcacg tcgtatttgg gactatgaca 3991 atgaattaaa aaaacgtttc aaaaattggg acgacttaat gaaagcattt ccagagcaag cgaaagactt 4061 atttagaggt tggttaaacg acggtacgat tgacagtatt attcatgacg agtttaaaaa atatagcgca 4131 ggattaacat cggcatttgc tttatttaaa gttactgaaa tgaaacaaat gaatgacttt aaatcagaag 4201 ttaaagactt aattaaagat attgaccgtt tcgttaatgg gtttgaatta aatgagcttg aaccaagtt 4271 tgtgatgggc tttggtggta ttcgcaacgc agttaaccaa tctattaata ttgataaaga aacaaatcac 4341 atgtactcta cacaatccga ttctcaaaaa cctgaaggtt tttggataaa taaattaaca cctagtggtg 4411 acttaatttc aagcatgcgt attgtacagg gtggtcatgg tacaacaatc ggattagaac gtcaatccaa 4481 tggtgaaatg aaaatctggt tacatcacga tggtgttgca aaactgttac aagtcgcata taaagataat 4551 tatgtattag atttagaaga ggctaaaggt ttaacagatt atacaccaca gtcactttta aacaaacaca 4621 catttacacc gttaattgat gaagcaaatg acaaactcat tttaagattc ggtgacggaa caatacaggt 4691 tcgttcaaga gcagacgtaa aaaatcacat tgataatgta gaaaaagaaa tgacaattga taattcagaa WO 00/32825 PCT/IB99/02040 267 4761 aacaatgata atcgttggat gcaaggcatt gctgttgatg gtgatgattt atactggtta agtggtaaca 4831 gttcagttaa ttcacatgtt caaatcggta aatattcatt aacaacaggt caaaagattt atgattatcc 4901 atttaagtta tcatatcaag acggtattaa tttcccacgt gataacttta aagagcctga gggtatttgc 4971 atttatacaa atccaaaaac aaaacgtaaa tcgttattac ttgctatgac aaacggcggt ggtggaaaac 5041 gtttccataa tttatatggt ttcttccaac ttggtgagta tgaacacttt gaagcattac gcgcaagagg 5111 ttcacaaaac tataaattaa caaaagacga cggtcgtgca ttatctattc cagaccatat cgacgattta 5181 aatgacttaa cgcaagctgg tttttattat attgacgggg gtactgcaga aaaacttaag aatatgccaa 5251 tgaatggtag caagcgtata attgacgctg gttgtttcat taatgtatac cctacaacac aaacattagg 5321 tacggttcaa gaattaacac gtttctcaac aggtcgtaaa atggttaaaa tggtgcgtgg tatgacttta 5391 gacgtattta cgttaaaatg ggattatgga ttatggacaa caatcaaaac tgacgcacca tatcaagaat 5461 atttggaagc aagtcaatac aataactgga ttgcttatgt aacaacagct ggtgagtatt acattacagg 5531 taaccaaatg gaattattta gagacgcgcc agaagaaatt aaaaaagtgg gtgcatggtt acgtgtgtca 5601 agtggtaacg cagtcggtga agtaagacaa acattagagg ctaatatatc ggaatataaa gaattcttca 5671 gtaatgttaa tgcggaaaca aaacatcgtg aatatggttg ggtagcaaaa catcaaaaat aggagtgata 5741 taaatgaaat cacaacaaca agcaaaagaa tggatatata agcatgaggg ggcaggtgtt gactttgatg 5811 gtgcatatgg atttcaatgt atggacttat cagttgctta tgtgtattac attactgacg gtaaagttcg 5881 catgtggggt aatgctaaag acgcgataaa taatgacttt aaaggtttag cgacggtgta taaaaataca 5951 ccgagcttta aacctcaatt aggggacgtt gctgtatata caaatggaca atatggacat attcaatgtg 6021 tgttaagtgg aaatcttgat tattatacat gcttagaaca aaactggtta ggcggcggtt ttgacggttg 6091 ggaaaaagca accattagaa cacattatta tgacggtgta actcacttta ttagacctaa attttcaggt 6161 agtaatagca aagcattaga aacatcaaaa gtaaatacat ttggaaaatg gaaacgaaac caatacggca 6231 catattatag aaatgaaaat ggtacattta catgtggttt tttaccaata tttgcacgtg tcggtagtcc 6301 aaaattatca gaacctaatg gctattggtt ccaaccaaac ggttatacac catataacga agtttgttta 6371 tcagatggtt acgtatggat tggttataac tggcaaggca cacgttatta tttaccagtg cgccaatgga 6441 atggaaaaac aggtaatagt tacagtgttg gtattccttg gggggtgttc tcataatggg tattttagcc 6511 tttttctttg aatttagttg gaaaagatac aaataagagg tgtaaacaat ggctgataga atcgtaagaa 6581 gtttaagaca agttgaaaca attgaacgtt tattggagga aaaaaatgag aaagttaacg aattttaagt 6651 ttttctataa cacaccgttt acagactatc aaaacacgat tcattttaat agtaataaag aacgtgatga 6721 ttatttttta aatggtcgtc attttaaatc gttagactat tcaaaacaac cgtataattt tatacgtgat 6791 agaatggaaa tcaatgttga tatgcagtgg catgacgcac aaggtattaa ctacatgacg tttttatcag 6861 attttgagga tagaagatat tacgcttttg taaaccaaat cgaatacgtg aatgacgttg tggttaaaat 6931 atattttgtc attgatacca ttatgacgta tacacaaggg aatgtattag agcaactctc aaacgtcaat 7001 attgaacgtc aacatttatc aaaacgcacg tataactata tgttaccaat gttacgtaat aatgatgatg 7071 tgttaaaagt atcaaataaa aactatgttt ataaccaaat gcaacaatat ttggaaaatt tagtattatt 7141 ccagtcaagc gctgatttat caaagaaatt tggtactaaa aaagagccaa acttagatac gtcaaaaggt 7211 acgatttatg acaatatcac atcaccagtc aacttatacg ttatggaata tggtgacttt attaacttta 7281 tggataaaat gagtgcctat ccatggatta cgcaaaactt tcaaaaggtt caaatgttac ctaaagactt 7351 tattaataca aaagacttag aggacgttaa aaccagtgaa aaaattacag gattaaaaac attaaaacag 7421 ggtggtaaat caaaagaatg gagtctaaaa gatttatcat taagtttctc aaatcttcaa gagatgatgt 7491 tatctaaaaa agatgaattt aaacatatga tacgtaatga gtatatgaca attgaatttt atgactggaa 7561 tggaaatacg atgttactcg acgctggtaa gatttcacaa aaaactggtg ttaagttacg tacaaaatca 7631 attattggtt atcataatga agttcgagta tatccagtag attataacag tgctgaaaac gacagaccaa 7701 tactcgctaa aaataaagaa atattgattg atacgggttc attcttaaat acaaatataa catttaatag 7771 ttttgcacaa gtaccaatat taatcaataa tggtatctta ggacaatcac aacaagccaa ccgacaaaaa 7841 aatgcagaaa gtcaattaat tacaaatcgt attgataatg tattaaatgg tagcgacccg aaatcacgct 7911 tttatgacgc tgtgagtgta gcaagtaatt taagtccaac tgctttattt ggtaagttta atgaagaata 7981 taatttctac aaacaacaac aagctgaata taaagattta gccttacaac caccttctgt aactgaatca 8051 gaaatgggca acgcattcca aattgcgaat agcattaacg gtttaacgat gaaaattagt gtaccgtcac 8121 ctaaagaaat tacattttta caaaaatatt atatgttgtt tggttttgaa gtgaatgact ataattcatt 8191 tattgaacca attaacagta tgactgtttg caattattta aaatgtacag gtacgtatac tatacgtgac 8261 atcgacccca tgttaatgga acaattaaaa gcaattttag aatctggtgt aagattttgg cataatgacg 8331 gttcaggtaa tccaatgtta caaaatccat taaataacaa atttagagag ggggtataat atgaacgaag 8401 taaaattcag atttacagac tcagaagcgt ttcacatgtt tatatacgct ggggatttaa aattactcta 8471 ctttttattt gtattaatgt tcgttgatat tattacaggt atttcaaaag caattaaaaa taataactta 8541 tggtcaaaaa aatcaatgag aggattttct aaaaaattat tgatattctg tattatcatt ttagcaaaca 8611 tcattgacca gattttacaa ttaaaaggtg gtctactcat gattacaata ttttattata ttgcaaatga 8681 gggactttct attgtagaaa attgtgcaga aatggacgta ttagtaccag aacaaattaa agataaatta 8751 agagtcatta aaaatgatac tgaaaagagt gataacaatg aacgatcaag agaagataga taaatttacg 8821 cattcctata ttaatgatga ttttggttta acgatagacc agttagtccc taaagtaaaa ggatatgggc 8891 gctttaatgt atggcttggt ggtaatgaaa gtaaaatcag acaagtatta aaagcagtaa aagagatagg 8961 tgtttcacct actctttttg ccgtatatga aaaaaatgag ggttttagtt ctggacttgg ttggttaaac 9031 catacgtctg cacgtggtga ttatttaaca gatgctaaat tcatagcaag aaagttagta tcacaatcaa 9101 aacaagctgg acaaccgtct tggtatgacg caggtaacat cgtccacttt gtaccacaag acgtacaaag 9171 aaaaggtaat gcagattttg caaaaaatat gaaagcaggt acaattggac gtgcatatat tccattaaca 9241 gcagctgcta cttgggcggc atattatcct ttaggtttga aagcatcata taacaaagta caaaactatg 9311 gtaatccatt tttagacggt gcgaatacta ttctagcttg gggtggtaaa ttagacggta aaggtggatc 9381 acctagtgat tcgtctgaca gtggtagtag tggtgacagt ggtagttcac tactcgcttt agcaaaacaa 9451 gccatgcaag aattattaaa aaaaatacaa gacgcattac aatgggacgt tcatagtatt ggtagtgata 9521 aattttttag taatgattat tttacattag aaaaaacatt taacaacaca tatcatatta aaatgacgat . 9591 tggtttactt gattcattaa aaaaactgat tgatagcgtt caagtagata gtgggagtag tagttctaat 9661 cctactgatg atgacggaga ccataaacca attagtggta aatcagtcaa gccaaatgga aaaagtggtc 9731 gtgtgattgg tggtaactgg acatatgcac agttaccaga aaaatataaa aaagcaattg gtgtaccttt 9801 attcaaaaaa gaatacttat acaaaccagg taacatattt cctcaaacgg gtaatgcagg acaatgtaca 9871 gaattaacat gggcgtatat gtcacaacta catggtaaaa gacaacctac cgacgacggt caaataacaa 9941 acggtcagcg tgtatggtac gtctataaaa agttaggtgc aaaaacaaca cataatccaa cagtaggtta 10011 tggtttctct agtaaaccac catacttaca agcaactgca tatggtattg gtcacacagg tgttgttgta WO 00/32825 PCT/IB99/02040 268 10081 gcagtttttg aagatggttc gtttttagtt gcaaactata atgtaccacc atatgttgca ccatcacgtg 10151 tggtattgta tacactcatt aatggcgtac caaataatgc tggtgataat attgtattct ttagtggtat 10221 tgcttaatta actatgctat aatgaacaca tgctagtaat gctagtaaat aaaatacaaa acataatcaa 10291 ttttcgtaca catttttcat gttatctcaa aaagaaaagg agactgttat tttaacagtt gccttttttt 10361 atttcatcat gttcacgttt taatatatgc aaatcagatt tgttatgtac tgaacgttca actggaaata 10431 agtcgttaag tgaaaatgaa ccgatgtcac tttcaatata aagaatatca tcaaattgac tatggtcgaa 10501 attttctcta gcgtctttta atataaattc acgtttcata ttaagttcat cagtaaaata ttcatcatat 10571 acattaccac atacaatttc agttttagac ggatatatcg atattgtacc ttgctcatta tagatacttt 10641 tattgttttc aataatggca ccgtcaaaga attgttcacg tacaaaggtt tcaaaatcga cgcttgtatc 10711 aaaggcgttt ttcggtatac cagcagaagc aattttaatc tttccattca cttcatatgc atatttctta 10781 tgattcagta caaacatctt atctatctgt tcgttttcaa tatcccattt acctaaggct atcgggtcga 10851 ataaactggg gttcaataag ggtttaacaa cggatttcat atacaaacta tcagtatcgc aataaataaa 10921 attgtcgtca atttcacttt ccgttaagta ttggaaagga accaataagt tatacaatga acgtgatgtg 10991 acaaatgtag agaataatat attacgttca gtgtttttgt aaccgttaat gatattgtat agttcattgt 11061 tatcatctaa acggaataag ttaaaatgtg aacgtaatgc aggtatgcca tataatccat ttaaaacgac 11131 tttagataac ataacctcct catttgagta tgggtgttcg ttgatatcat cagtaatgtg atagtcgtaa 11201 ggtgatgtca tattgatttt gttttttaac ttaccttgtg ttttaataaa atagttttga aaaataatat 11271 cacgtgcatg aaagtattca cattcatata taacaaacga attaacacgt atatgcatgc aatcaatacc 11341 cgtaatgtct tgaatcattc ttaatgtatt tgtattgata ttaacgtaat cattatcatt attatagtat 11411 tttacaatca tttgacgtaa tacacgtgat ttaattttaa ttaataaatc atcgttaaat acatctttat 11481 caatcttata taatgaaaaa taattgtcat catctaaaaa agtagggatt aacgttggtt ctgaatagtg 11551 ttcgtaaaag tataaccatg ttggaatttt ttcatgatac atcacataag gataactcga attgatgtca 11621 atagaaaaac aaggctcatc aattagtttg tttatgtatt tggtgttata catatttaaa ccaccacgat 11691 agaatgattt aatatagtca taaaaattca tatcatggaa atgataatgt gtataagata ttttaatatc 11761 ttgatattgg ttgagtaact gaaaacgtgt catttcatta ttcaagtaag attccataat attcaatgaa 11831 aatgttaatt tgttatagtc aaaatttgga aatatatcac tataatgaat atggcacata cctaatataa 11901 tcacgtcatt atgaatgtat gtaagttgtt caggtgtgag ttttgcaaaa catttcacag catagtcata 11971 ggcttcacta tcattcatat cattatcttt atcaaaaatc gtataattaa aatctgtttt aagttgtgat 12041 tctgttaaat aaccaccatc aagtaatttc ttacctaatg ttgcaattga tgtattggtt ttcataaagt 12111 tatcaataat attaaattta aaaccattta aaaacattgt taaatctaaa ttgattgaag atttaacacg 12181 tttttctaaa attacatttt gatttttggc taaaatagta gcctctttca tttttaatgt gtgttcattt 12251 tcttctgcag attttaaata tatattttcg cgtgtaatat tatcaaaata acgcatggtg tctttaagta 12321 aaaaatgatt atcgtattta ttacagttat gtgcaatcat gataatatct gtttttgatt ttgtgattgt 12391 atcacgtctt ttcacatacg tataaaatgc gtcataaaaa gattcgaaac tcggaaatac ttcaacatca 12461 atttcataac cattaaacca accaattgct acagaataag taacgttttt atatttggtt ggtttttttc 12531 gtccgttaac tttattgtac gctaatgttt ctatatccca gtataaaatc attcgacgtt catgtttatg 12601 atattgcatg cattctagta atcccataat cttacacacc ttttataagc catattgttt cattagatac 12671 tttttcgtat tctctatata gttatcttcg tatatttttt cttttctttc aaactcactc atatttttct 12741 tcatttcatt ttttatatga aattttataa ttttattcat atctaaatat aaatatctat cattatcaac 12811 cacgtaattt ttagagtaag cattgtcaaa atgtaaattg cttggattgt agtaataacg ttccatgttt 12881 tctttataaa acatatcatc acgtaaatag gtaacatgat tgtctatatc cctaatttta gtacaaaatt 12951 catattgttt tgtatatggt acaacgataa tatttgtcat aaaagtagtt acattataca tgactttaat 13021 atatttatca tcagttttga tatagaagaa atcaccgttt tgattgatgt gatttcttaa attatcatcc 13091 gccaaattat attcgttaaa ttcaaattct ccagttgtca tagcgtcgtc atttgaatta aacgcacgtg 13161 tgttacgttt ttcattcacg taatcgtttc gtcgcatttc taaaaaaatg tttttgtaaa gtcttgatgt 13231 attcatttta tgcttttgta ataaattgta tatatttaaa ttggataata taggacttga aaagttgact 13301 gcattaccta gtaaaaacat tttagggaat ccaatataat caacgttacc atggttacgg tcgattgatt 13371 catatattgt ttttaactta tcccactcat caattaaata atcatcttca agtgctaaaa actcatcata 13441 tataataata ggatagtgtt ttaaaaagtt agaatgatat tttaaatcag tggcactatt caaatctgta 13511 atcacaccaa tttctttatc ttgatagata atagctaaat agtccctagc acttctgaac gtgacacgtt 13581 ttgatttaaa tagtggattt tcatctatga tttcttcaat aaaatcacgg taagcgtcac gtaatgtata 13651 atgacgtgat aataaagtaa attttatatc aagtttaata gctaaataaa taaaaaatga aacatagttg 13721 aacgattttc catcagaacg gtttgaaata gatatataat aatctatatc atcattcata agttcatcaa 13791 ctaattctat ttgattatac ttatctggga ttttttttct gacatgattg acagcatttt gataatctct 13861 taccatgtct aaacgatttt gttttaccat gtttttgctc cttgtaatag tttatgatgt cgtttacagt 13931 gttaaattta ttcgtcaaat gttgcataat ataaaaagtt atacctcaca tcttcatcat caatatttgt 14001 cactggtcta tctgatttac caatttcttt atataaagta tcgatttctt taatatattt atacattgaa 14071 gaattattat ttttagcttg taaattatat aaagcgtatt tatgcttttt agcgttttta ttattagaat 14141 catcattacg gttatatatt tcaagaatat aatttaattt tttatgtctt gaacctctta ccaatgatac 14211 agcatttaca tatgatacgt ttctttcttt aggaaaatag ggcagatgtg caaaatgttt ccatgtgtca 14281 atgtacgcct cttgtaaatc tttatcatca aatttaaaat taacattact aaaatcattt aaaaataaat 14351 ctttttcttg ctcttttcta gcttctcttt cttttttcca tctatccatt tcagacgtat gtctaaccaa 14421 tgttatcaac ctccatataa agcataaata accattaaaa agataatata gaatataatc aatgtagtga 14491 ataaaacacc aaatgacacg cgtatatgca gtgtcataag tatgataagt gtaattaaaa atgctaaaag 14561 gaaaacaatg gctatgttta ataggttatt catggtcaat cactttccca ttatcgtata tgactttgtt 14631 ttgataaata atcattaatt cgctttcaag aggtttatca aaatttgata atacgtcgtc aattgtaacg 14701 tttaataaaa tttctcttat taattcatta cttaaataat ttctataata aaatacaagt atattaaaaa 14771 catgtttttt aatatcaatg tcgatatcta acgtaaataa ctctttttca atttcaaaat catcatattg 14841 tttgtcaaac tcaatataca catcacccat atttattttt actatacatt ttttattaga tgaagtaaat 14911 ttttcaaatt tatcattata ataatctcta tttgttaaaa ggtaataaat taaattattt aatctaaaag 14981 tagttttaat tttcattttt atatctcctt aatgtattct atgatatacg cgtatttttt agtgaicagg 15051 ttatattcat aatatgaata tacaacttta gcgtcatata aatcttcaaa cattgagatt tgatgtggaa 15121 aatgtccttt aatctcatcg caatataata ataccgtttt gtatttacgt tccatttaaa cacctcataa 15191 aaaatagggg ataagtatcc cctatgaaat tgtattaaaa tgatacttga ccaaaattga ttgagtaacc 15261 tttttgacct tttttgtttt catattcata aattgtgaat tgaacttctc cagcattgat aatgtcaaca 15331 acgtcctcat ctgctctcat ttctttaatt aattctgtta agtggttcgg taagtttacg ttatagtcat WO 00/32825 PCT/IB99/02040 269 15401 cagtgacgat aacaccttgt tcaccgaatt ttgattcttt gtttgtgaat aatgctctaa cgatatactc 15471 ttttttcata ccgtattttt ctactaattc tgatagtttg ataaattctc tttctttttc ctcaaattca 15541 aatctcgcta atgtgttttg gtgtcttgat aaaatatctt ttacgtttgt cattttattt ctcctcttat 15611 ttaaattatt tgctttctgc aattgcgatt tgtagtaaat cattgtaata aacttgaatt gttttcgttg 15681 tgcgtgtagt ggacaatagt ttacatgtgt ctggtaataa ttcttttgct tgtgttttgg ttaaatgata 15751 ctcgtgaagt ggtaaaaatt cctcaatgta ttcattatca tcatctaagt aatgaagtat ataacctttg 15821 acacgtaagg taacaatgtc gtcaactttc attattatat cactcctttc taaaaaacgt aaacgttata 15891 cgtttcataa aatcctttat gcatattcca ttgttctatt gggtcatcac cagcaatata agacaatatt 15961 gattctggtt tagtttcgtt gtttagttca tcatttaaga attgaacaac agaactatta tagtttaata 16031 atagttgttg gcaagccgat aataagttaa ttgcattgtc aaatgtataa gctggattcc attgaatcag 16101 tttattgaat agttgcaaca tttcagtata ggcttgtcct ttttcttctg gtgcattatc aacattaacc 16171 attattatca cttcctaata aagttgaaat tacgcgtaaa acagaattat gatttaaatc ttcaatttca 16241 tcaatgtcaa catcataaaa tgaaatttca ttttctgttc tatcaaataa cgctatacat aaacttccat 16311 tcttaaaacg aaaaacatgc ttcaactcaa tgttttttgt ttcattttcc atttttgtta ctccttgttt 16381 tgattacata cttagtatag caaacgttta aaagttttgt caatagtttt tcttaaaaaa gtttaaataa 16451 ttttaaaact actatttaat agaagaaata agattttaag ttcaaatcat aattttgaat aaaagtcaat 16521 agatacataa attttgtatt tgatgaatat gtaataggtt agataagttg gttaagttgt tgcacagtat 16591 ttttaagttt agtaaagaaa tgataagtaa atttataagt tttgatttgt ataatcgttt attttaaacc 16661 ggtggggt WO 00/32825 PCT/I B99/02040 270 Table 17 Phage 44AHJD ORFs list nbName Frame Position Size (a.a.) Key words 1 44AHJDORFOOl -1 1 10342..12627 761 DNA polymerase; 2 44AHJDORFOO2 3 3789..5732 647 Techoic acid; Staph; 3 44AHJDORFOO3 2 6626..8389 587 Tail; 4 44AHJDORFOO4 1 8764..10227 1 487 Serine protease motit 5 44AHJDORFOO5 -1 12643..13890 415 16 44AHJDORFOO6 2 801..2029 1 408 7 44AHJDORFO07 1 2044..3027 327 Upper collar: 8 44AHJDORFO08 2 3020..3775 251 Lower collar 9 44AHJDQRFO09 2 5744..6496 250 Amidase; Staph; 10 44AHJDORF010 -2 13938..14420 160 11 44AHJDORF012 3 8391..8813 140 Holin; 12 44AHJDORF013 -2 14586..14996 136 13 44AHJDORF1 13 1 199..600 133 ______________ 14 44AHJDORF0l11 -2 15225..15593 122 15 44AHJDORF1 14 -2 15870..16172 100 16 44AHJDORF014 3 6243..6521 92 _________________ 17 44AHJDORF015 1 15403..15645 80 18 44AHJDORF016 -1 15616..15852 78 19 44AHJDORF017 -2 10536..10757 73 20 44AHJDORF018 -1 886..1098 70 21 44AHJDORF019 -2 9630..9836 68 22 44AHJDORF121 -1:: 16165..16362 65 23 44AHJDORF020 2 1 13865..14053 62 24 144AHJDORF123 2 614..796 60 25 44AHJDORF021 -2 5634..5816 60 26 44AHJDORF023 -2 6315..6494 59 27 44AHJDORF024 1 14275..14451 58 28 44AHJDORF025 -3 14999..15175 58 29 44AHJDORF026 -3 14426..14593 55________________ 30 44AHJDORF027 1 1291 6..1 3080 54 31 44AHJDORF029 -1 15019..15183 54 32 44AHJDORF028 -3 9071 ..9235 54 33 44AHJDORF030 3 14487-.14648 53_________________ 34 44AHJDORF031 2 11039..11191 50 35 44AHJDORF135 3 693..842 49 36 144AHJDORF033 -1 3646..3795 49_________________ 37 144AHJDORF032 -2 9306..9455 49_________________ 38 44AHJDORF034 -3 14000..14146 48 ________________ 39 44AHJDORF035 -3 13811..13957 48 ________________ 40 44AHJDORF036 -3 10019..10165 48 ________________ 41 44AHJDORF022 -3 8468..8611 1 47 42 44AHJDORF037 1 14788..14931 1 47 43 44AHJDORF038 -2 3528..3671 1 47 44 44AHJDORF039 3 1743..1883 46 ________________ 45 44AHJDORF040 2 9740..9877 45 46 44AHJDORF041 2 15836..15973 45 47 44AHJDORF042 -1 5014..5151 45 48 44AHJDORF043 -1 4402..4539 45 49 44AHJDORF044 1 -2 12783..12917 44 50 44AHJDORF149 -2 639..770 43 51 44AHJDORF046 1 4891 ..5019 42 ________________ 52 44AHJDORF047 1 11911..12039 42 53 44AHJDORF045 2 10655..10783 1 42 54 44AHJDORF048 1 -3 1 15212..15340 1 42 ________________ 55 44AHJDORF049 3 1 5784..5909 41 56 44AHJDORF050 3 1 13158..13283 41 ________________ 57 44AHJDORF051 -2 10944..11066 40 - 58 44AHJDORF052 -3 14216..14338 40 59 44AHJDORF053 3 3348..3467 39 60 44AHJDORF054 3 7551..7670 39 61 44AHJDORF055 3 15705..15821 38 62 44AHJDORF056 1 5512..5625 37 63 44AHJDORF057 2 10121..10231 1 36 64 44AHJDORF058 3 10767..10877 1 36 WO 00/32825 PCTIB99/02040 271 65 44AH-JDORF164 -1 592.1702 36 66 44AHJDJORF059 -2 8250..8360 36 ________________ 67 44AHJDORF060 -2 6147..6257 36 ________________ 68 44AHJDORF061 2 15551..15658 35 _______________ 69 44AHJDORF062 1 4285..4389 34 ________________ 70 44AHJDORF063 -3 9383..9487 34 ________________ 71 44AHJORF065 1 5029..5130 33 ________________ 72 44AHJDORF064 2 2609..2710 33 73 44AHJDORF066 -2 10380..10481. 33 WO 00/32825 PCT/IB99/02040 272 Table 18 Predicted amino acid sequences 44AHJDORFO01 12627 atgggattactagaatgcatgcaatatcataaacatgaacgtcgaatgattttatactgggatatagaaacattagcgtacaat 1 M G L L E C M Q Y H K H E R R M I L Y W D I E T L A Y N 12543 aaagttaacggacgaaaaaaaccaaccaaatataaaaacgttacttattctgtagcaattggttggtttaatggttatgaaatt 29 K V N G R K K P T K Y K N V T Y S V A I G W F N G Y E I 12459 gatgttgaagtatttccgagtttcgaatctttttatgacgcattttatacgtatgtgaaaagacgtgatacaatcacaaaatca 57 D V E V F P S F E S F Y D A F Y T Y V K R R D T I T K S 12375 aaaacagatattatcatgattgcacataactgtaataaatacgataatcattttttacttaaagacaccatgcgttattttgat 85 K T D I I M I A H N C N K Y D N H F L L K D T M R Y F D 12291 aatattacacgcgaaaatatatatttaaaatctgcagaagaaaatgaacacacattaaaaatgaaagaggctactattttagcc 113 N I T R E N I Y L K S A E E N E H T L K M K E A T I L A 12207 aaaaatcaaaatgtaattttagaaaaacgtgttaaatcttcaatcaatttagatttaacaatgtttttaaatggttttaaattt 141 K N Q N V I L E K R V K S S I N L D L T M F L N G F K F 12123 aatattattgataactttatgaaaaccaatacatcaattgcaacattaggtaagaaattacttgatggtggttatttaacagaa 169 N I I D N F M K T N T S I A T L G K K L L D G G Y L T E 12039 tcacaacttaaaacagattttaattatacgatttttgataaagataatgatatgaatgatagtgaagcctatgactatgctgtg 197 S Q L K T D F N Y T I F D K D N D M N D S E A Y D Y A V 11955 aaatgttttgcaaaactcacacctgaacaacttacatacattcataatgacgtgattatattaggtatgtgccatattcattat 225 K C F A K L T P E Q L T Y I H N D V I I L G M C H I H Y 11871 agtgatatatttccaaattttgactataacaaattaacattttcattgaatattatggaatcttacttgaataatgaaatgaca 253 S D I F P N F D Y N K L T F S L N I M E S Y L N N E M T 11787 cgttttcagttactcaaccaatatcaagatattaaaatatcttatacacattatcatttccatgatatgaatttttatgactat 281 R F Q L L N Q Y Q D I K I S Y T H Y H F H D M N F Y D Y 11703 attaaatcattctatcgtggtggtttaaatatgtataacaccaaatacataaacaaactaattgatgagccttgtttttctatt 309 I K S F Y R G G L N M Y N T K Y I N K L I D E P C F S I 11619 gacatcaattcgagttatccttatgtgatgtatcatgaaaaaattccaacatggttatacttttacgaacactattcagaacca 337 D I N S S Y P Y V M Y H E K I P T W L Y F Y E H Y S E P 11535 acgttaatccctacttttttagatgatgacaattatttttcattatataagattgataaagatgtatttaacgatgatttatta 365 T L I P T F L D D D N Y F S L Y K I D K D V F N D D L L 11451 attaaaattaaatcacgtgtattacgtcaaatgattgtaaaatactataataatgataatgattacgttaatatcaatacaaat 393 I K I K S R V L R Q M I V K Y Y N N D N D Y V N I N T N 11367 acattaagaatgattcaagacattacgggtattgattgcatgcatatacgtgttaattcgtttgttatatatgaatgtgaatac 421 T L R M I Q D I T G I D C M H I R V N S F V I Y E C E Y 11283 tttcatgcacgtgatattatttttcaaaactattttattaaaacacaaggtaagttaaaaaacaaaatcaatatgacatcacct 449 F H A R D I I F Q N Y F I K T Q G K L K N K I N M T S P 11199 tacgactatcacattactgatgatatcaacgaacacccatactcaaatgaggaggttatgttatctaaagtcgttttaaatgga 477 Y D Y H I T D D I N E H P Y S N E E V M L S K V V L N G 11115 ttatatggcatacctgcattacgttcacattttaacttattccgtttagatgataacaatgaactatacaatatcattaacggt 505 L Y G I P A L R S H F N L F R L D D N N E L Y N I I N G 11031 tacaaaaacactgaacgtaatatattattctctacatttgtcacatcacgttcattgtataacttattggttcctttccaatac 533 Y K N T E R N I L F S T F V T S R S L Y N L L V P F Q Y 10947 ttaacggaaagtgaaattgacgacaattttatttattgcgatactgatagtttgtatatgaaatccgttgttaaacccttattg 561 L T E S E I D D N F I Y C D T D S L Y M K S V V K P L L 10863 aaccccagtttattcgacccgatagccttaggtaaatgggatattgaaaacgaacagatagataagatgtttgtactgaatcat 589 N P S L F D P I A L G K W D I E N E Q I D K M F V L N H 10779 aagaaatatgcatatgaagtgaatggaaagattaaaattgcttctgctggtataccgaaaaacgcctttgatacaagcgtcgat 617 K K Y A Y E V N G K I K I A S A G I P K N A F D T S V D 10695 tttgaaacctttgtacgtgaacaattctttgacggtgccattattgaaaacaataaaagtatctataatgagcaaggtacaata 645 F E T F V R E Q F F D G A I I E N N K S I Y N E Q G T I 10611 tcgatatatccgtctaaaactgaaattgtatgtggtaatgtatatgatgaatattttactgatgaacttaatatgaaacgtgaa 673 S I Y P S K T E I V C G N V Y D E Y F T D E L N M K R E 10527 tttatattaaaagacgctagagaaaatttcgaccatagtcaatttgatgatattctttatattgaaagtgacatcggttcattt 701 F I L K D A R E N F D H S Q F D D I L Y I E S D I G S F 10443 tcacttaacgacttatttccagttgaacgttcagtacataacaaatctgatttgcatatattaaaacgtgaacatgatgaaata 729 S L N D L F P V E R S V H N K S D L H I L K R E H D E I 10359 aaaaaaggcaactgttaa 10342 757 K K G N C * 44AHJDORFOO2 3789 atggcatataatgaaaacgattttaaatattttgatgacattcgtccatttttagacgaaatttataaaacgagagaacgttat 1 M A Y N E N D F K Y F D D I R P F L D E I Y K T R E R Y 3873 acaccgttttacgatgatagagcagattataatactaattcaaaatcatattatgattatatttcaagattatcaaaactaat_ 29 T P F Y D D R A D Y N T N S K S Y Y D Y I S R L S - I 3957 gaagtattagcacgtcgtatttgggactatgacaatgaattaaaaaaacgtttcaaaaattgggacgacttaatgaaagcattt 57 E V L A R R I W D Y D N E L K K R F K N W D D L M K A F 4041 ccagagcaagcgaaagacttatttagaggttggttaaacgacggtacgattgacagtattattcatgacgagtttaaaaaatat 85 P E Q A K D L F R G W L N D G T I D S I I H D E F K K Y 4125 agCgcaggattaacatcggcatttgctttatttaaagttactgaaatgaaacaaatgaatgactttaaatcagaagttaaagac 113 S A G L T S A F A L F K V T E M K Q M N D F K S E V K D 4209 ttaattaaagatattgaccgtttcgttaatgggtttgaattaaatgagcttgaaccaaagtttgtgatgggctttggtggtatt WO 00/32825 PCT/IB99/02040 273 141 L I K D I D R F V N G F E L N E L E P K F V M G F G G I 4293 cgcaacgcagttaaccaatctattaatattgataaagaaacaaatcacatgtactctacacaatccgattctcaaaaacctgaa 169 R N A V N Q S I N I D K E T N H M Y S T Q S D S Q K P E 4377 ggtttttggataaataaattaacacctagtggtgacttaatttcaagcatgcgtattgtacagggtggtcatggtacaacaatc 197 G F W I N K L T P S G D L I S S M R I V Q G G H G T T I 4461 ggattagaacgtcaatccaatggtgaaatgaaaatctggttacatcacgatggtgttgcaaaactgttacaagtcgcatataaa 225 G L E R Q S N G E M K I W L H H D G V A K L L Q V A Y K 4545 gataattatgtattagatttagaagaggctaaaggtttaacagattatacaccacagtcacttttaaacaaacacacatttaca 253 D N Y V L D L E E A K G L T D Y T P Q S L L N K H T F T 4629 ccgttaattgatgaagcaaatgacaaactcattttaagattcggtgacggaacaatacaggttcgttcaagagcagacgtaaaa 281 P L I D E A N D K L I L R F G D G T I Q V R S R A D V K 4713 aatcacattgataatgtagaaaaagaaatgacaattgataattcagaaaacaatgataatcgttggatgcaaggcattgctgtt 309 N H I D N V E K E M T I D N S E N N D N R W M Q G I A V 4797 gatggtgatgatttatactggttaagtggtaacagttcagttaattcacatgttcaaatcggtaaatattcattaacaacaggt 337 D G D D L Y W L S G N S S V N S H V Q I G K Y S L T T G 4881 caaaagatttatgattatccatttaagttatcatatcaagacggtattaatttcccacgtgataactttaaagagcctgagggt 365 Q K I Y D Y P F K L S Y Q D G I N F P R D N F K E P E G 4965 atttgcatttatacaaatccaaaaacaaaacgtaaatcgttattacttgctatgacaaacggcggtggtggaaaacgtttccat 393 I C I Y T N P K T K R K S L L L A M T N G G G G K R F H 5049 aatttatatggtttcttccaacttggtgagtatgaacactttgaagcattacgcgcaagaggttcacaaaactataaattaaca 421 N L Y G F F Q L G E Y E H F E A L R A R G S Q N Y K L T 5133 aaagacgacggtcgtgcattatctattccagaccatatcgacgatttaaatgacttaacgcaagctggtttttattatattgac 449 K D D G R A L S I P D H I D D L N D L T Q A G F Y Y I D 5217 gggggtactgcagaaaaacttaagaatatgccaatgaatggtagcaagcgtataattgacgctggttgtttcattaatgtatac 477 G G T A E K L K N M P M N G S K R I I D A G C F I N V Y 5301 cctacaacacaaacattaggtacggttcaagaattaacacgtttctcaacaggtcgtaaaatggttaaaatggtgcgtggtatg 505 P T T Q T L G T V Q E L T R F S T G R K M V K M V R G M 5385 actttagacgtatttacgttaaaatgggattatggattatggacaacaatcaaaactgacgcaccatatcaagaatatttggaa 533 T L D V F T L K W D Y G L W T T I K T D A P Y Q E Y L E 5469 gcaagtcaatacaataactggattgcttatgtaacaacagctggtgagtattacattacaggtaaccaaatggaattatttaga 561 A S Q Y N N W I A Y V T T A G E Y Y I T G N Q M E L F R 5553 gacgcgccagaagaaattaaaaaagtgggtgcatggttacgtgtgtcaagtggtaacgcagtcggtgaagtaagacaaacatta 589 D A P E E I K K V G A W L R V S S G N A V G E V R Q T L 5637 gaggctaatatatcggaatataaagaattcttcagtaatgttaatgcggaaacaaaacatcgtgaatatggttgggtagcaaaa 617 E A N I S E Y K E F F S N V N A E T K H R E Y G W V A K 5721 catcaaaaatag 5732 645 H Q K * 44AHJDORFOO3 6626 atgagaaagttaacgaattttaagtttttctataacacaccgtttacagactatcaaaacacgattcattttaatagtaataaa 1 M R K L T N F K F F Y N T P F T D Y Q N T I H F N S N K 6710 gaacgtgatgattattttttaaatggtcgtcattttaaatcgttagactattcaaaacaaccgtataattttatacgtgataga 29 E R D D Y F L N G R H F K S L D Y S K Q P Y N F I R D R 6794 atggaaatcaatgttgatatgcagtggcatgacgcacaaggtattaactacatgacgtttttatcagattttgaggatagaaga 57 M E I N V D M Q W H D A Q G I N Y M T F L S D F E D R R 6878 tattacgcttttgtaaaccaaatcgaatacgtgaatgacgttgtggttaaaatatattttgtcattgataccattatgacgtat 85 Y Y A F V N Q I E Y V N D V V V K I Y F V I D T I M T Y 6962 acacaagggaatgtattagagcaactctcaaacgtcaatattgaacgtcaacatttatcaaaacgcacgtataactatatgtta 113 T Q G N V L E Q L S N V N I E R Q H L S K R T Y N Y M L 7046 ccaatgttacgtaataatgatgatgtgttaaaagtatcaaataaaaactatgtttataaccaaatgcaacaatatttggaaaat 141 P M L R N N D D V L K V S N K N Y V Y N Q M Q Q Y L E N 7130 ttagtattattccagtcaagcgctgatttatcaaagaaatttggtactaaaaaagagccaaacttagatacgtcaaaaggtacg 169 L V L F Q S S A D L S K K F G T K K E P N L D T S K G T 7214 atttatgacaatatcacatcaccagtcaacttatacgttatggaatatggtgactttattaactttatggataaaatgagtgcc 197 I Y D N I T S P V N L Y V M E Y G D F I N F M D K M S A 7298 tatccatggattacgcaaaactttcaaaaggttcaaatgttacctaaagactttattaatacaaaagacttagaggacgttaaa 225 Y P W I T Q N F Q K V Q M L P K D F I N T K D L E D V K 7382 accagtgaaaaaattacaggattaaaaacattaaaacagggtggtaaatcaaaagaatggagtctaaaagatttatcattaagt 253 T S E K I T G L K T L K Q G G K S K E W S L K D L S L S 7466 ttctcaaatcttcaagagatgatgttatctaaaaaagatgaatttaaacatatgatacgtaatgagtatatgacaattgaattt 281 F S N L Q E M M L S K K D E F K H M I R N E Y M T I E F 7550 tatgactggaatggaaatacgatgttactcgacgctggtaagatttcacaaaaaactggtgttaagttacgtacaaaatcaatt 309 Y D W N G N T M L L D A G K I S Q K T G V K L R T K S I 7634 attggttatcataatgaagttcgagtatatccagtagattataacagtgctgaaaacgacagaccaatactcgctaaaaataaa 337 I G Y H N E V R V Y P V D Y N S A E N D R P I L A K N K 7718 gaaatattgattgatacgggttcattcttaaatacaaatataacatttaatagttttgcacaagtaccaatattaatcaataat 365 E I L I D T G S F L N T N I T F N S F A Q V P I L I N N 7802 ggtatcttaggacaatcacaacaagccaaccgacaaaaaaatgcagaaagtcaattaattacaaatcgtattgataatgtatta 393 G I L G Q S Q Q A N R Q K N A E S Q L I T N R I D N V L- 7886 aatggtagcgacccgaaatcacgcttttatgacgctgtgagtgtagcaagtaatttaagtccaactgctttatttggtaaettt 421 N G S D P K S R F Y D A V S V A S N L S P T A L P-G K F 7970 aatgaagaatataatttctacaaacaacaacaagctgaatataaagatttagccttacaaccaccttctgtaactgaatcagaa 449 N E E Y N F Y K Q Q Q A E Y K D L A L Q P P S V T E S E 8054 atgggcaacgcattccaaattgcgaatagcattaacggtttaacgatgaaaattagtgtaccgtcacctaaagaaattacattt 477 M G N A F Q I A N S I N G L T M K I S V P S P K E I T F 8138 ttacaaaaatattatatgttgtttggttttgaagtgaatgactataattcatttattgaaccaattaacagtatgactgtttg WO 00/32825 PCT/IB99/02040 274 505 L Q K Y Y M L F G F E V N D Y N S F I E P I N S M T V C 8222 aattatttaaaatgtacaggtacgtatactatacgtgacatcgaccccatgttaatggaacaattaaaagcaattttagaatct 533 N Y L K C T G T Y T I R D I D P M L M E Q L K A I L E S 8306 ggtgtaagattttggcataatgacggttcaggtaatccaatgttacaaaatccattaaataacaaatttagaagggggtataa 8389 561 G V R F W H N D G S G N P M L Q N P L N N K F R E G V * 44AHJDORF0O4 8764 atgatactgaaaagagtgataacaatgaacgatcaagagaagatagataaatttacgcattcctatattaatgatgattttggt 1 M I L K R V I T M N D Q E K I D K F T H S Y I N D D F G 8848 ttaacgatagaccagttagtccctaaagtaaaaggatatgggcgctttaatgtatggcttggtggtaatgaaagtaaaatcaga 29 L T I D Q L V P K V K G Y G R F N V W L G G N E S K I R 8932 caagtattaaaagcagtaaaagagataggtgtttcacctactctttttgccgtatatgaaaaaaatgagggttttagttctgga 57 Q V L K A V K E I G V S P T L F A V Y E K N E G F S S G 9016 cttggttggttaaaccatacgtctgcacgtggtgattatttaacagatgctaaattcatagcaagaaagttagtatcacaatca 85 L G W L N H T S A R G D Y L T D A K F I A R K L V S Q S 9100 aaacaagctggacaaccgtcttggtatgacgcaggtaacatcgtccactttgtaccacaagacgtacaaagaaaaggtaatgca 113 K Q A G Q P S W Y D A G N I V H F V P Q D V Q R K G N A 9184 gattttgcaaaaaatatgaaagcaggtacaattggacgtgcatatattccattaacagcagctgctacttgggcggcatattat 141 D F A K N M K A G T I G R A Y I P L T A A A T W A A Y Y 9268 cctttaggtttgaaagcatcatataacaaagtacaaaactatggtaatccatttttagacggtgcgaatactattctagcttgg 169 P L G L K A S Y N K V Q N Y G N P F L D G A N T I L A W 9352 ggtggtaaattagacggtaaaggtggatcacctagtgattcgtctgacagtggtagtagtggtgacagtggtagttcactactc 197 G G K L D G K G G S P S D S S D S G S S G D S G S S L L 9436 gctttagcaaaacaagccatgcaagaattattaaaaaaaatacaagacgcattacaatgggacgttcatagtattggtagtgat 225 A L A K Q A M Q E L L K K I Q D A L Q W D V H S I G S D 9520 aaattttttagtaatgattattttacattagaaaaaacatttaacaacacatatcatattaaaatgacgattggtttacttgat 253 K F F S N D Y F T L E K T F N N T Y H I K M T I G L L D 9604 tcattaaaaaaactgattgatagcgttcaagtagatagtgggagtagtagttctaatcctactgatgatgacggagaccataaa 281 S L K K L I D S V Q V D S G S S S S N P T D D D G D H K 9688 ccaattagtggtaaatcagtcaagccaaatggaaaaagtggtcgtgtgattggtggtaactggacatatgcacagttaccagaa 309 P I S G K S V K P N G K S G R V I G G N W T Y A Q L P E 9772 aaatataaaaaagcaattggtgtacctttattcaaaaaagaatacttatacaaaccaggtaacatatttcctcaaacgggtaat 337 K Y K K A I G V P L F K K E Y L Y K P G N I F P Q T G N 9856 gcaggacaatgtacagaattaacatgggcgtatatgtcacaactacatggtaaaagacaacctaccgacgacggtcaaataaca 365 A G Q C T E L T W A Y M S Q L H G K R Q P T D D G Q I T 9940 aacggtcagcgtgtatggtacgtctataaaaagttaggtgcaaaaacaacacataatccaacagtaggttatggtttctctagt 393 N G Q R V W Y V Y K K L G A K T T H N P T V G Y G F S S 10024 aaaccaccatacttacaagcaactgcatatggtattggtcacacaggtgttgttgtagcagtttttgaagatggttcgttttta 421 K P P Y L Q A T A Y G I G H T G V V V A V F E D G S F L 10108 gttgcaaactataatgtaccaccatatgttgcaccatcacgtgtggtattgtatacactcattaatggcgtaccaaataatgct 449 V A N Y N V P P Y V A P S R V V L Y T L I N G V P N N A 10192 ggtgataatattgtattctttagtggtattgcttaa 10227 477 G D N I V F F S G IA * 44AHJDORFOO5 13890 atggtaaaacaaaatcgtttagacatggtaagagattatcaaaatgctgtcaatcatgtcagaaaaaaaatcccagataagtat 1 M V K Q N R L D M V R D Y Q N A V N H V R K K I P D K Y 13806 aatcaaatagaattagttgatgaacttatgaatgatgatatagattattatatatctatttcaaaccgttctgatggaaaatcg 29 N Q I E L V D E L M N D D I D Y Y I S I S N R S D G K S 13722 ttcaactatgtttcattttttatttatttagctattaaacttgatataaaatttactttattatcacgtcattatacattacgt 57 F N Y V S F F I Y L A I K L D I K F T L L S R H Y T L R 13638 gacgcttaccgtgattttattgaagaaatcatagatgaaaatccactatttaaatcaaaacgtgtcacgttcagaagtgctagg 85 D A Y R D F I E E I I D E N P L F K S K R V T F R S A R 13554 gactatttagctattatctatcaagataaagaaattggtgtgattacagatttgaatagtgccactgatttaaaatatcattct 113 D Y L A I I Y Q D K E I G V I T D L N S A T D L K Y H S 13470 aactttttaaaacactatcctattattatatatgatgagtttttagcacttgaagatgattatttaattgatgagtgggataag 141 N F L K H Y P I I I Y D E F L A L E D D Y L I D E W D K 13386 ttaaaaacaatatatgaatcaatcgaccgtaaccatggtaacgttgattatattggattccctaaaatgtttttactaggtaat 169 L K T I Y E S I D R N H G N V D Y I G F P K M F L L G N 13302 gcagtcaacttttcaagtcctatattatccaatttaaatatatacaatttattacaaaagcataaaatgaatacatcaagactt 197 A V N F S S P I L S N L N I Y N L L Q K H K M N T S R L 13218 tacaaaaacatttttttagaaatgcgacgaaacgattacgtgaatgaaaaacgtaacacacgtgcgtttaattcaaatgacgac 225 Y K N I F L E M R R N D Y V N E K R N T R A F N S N D D 13134 gctatgacaactggagaatttgaatttaacgaatataatttggcggatgataatttaagaaatcacatcaatcaaaacggtgat 253 A M T T G E F E F N E Y N L A D D N L R N H I N Q N G D 13050 ttcttctatatcaaaactgatgataaatatattaaagtcatgtataatgtaactacttttatgacaaatattatcgttgtacca 281 F F Y I K T D D K Y I K V M Y N V T T F M T N I I V V P 12966 tatacaaaacaatatgaattttgtactaaaattagggatatagacaatcatgttacctatttacgtgatgatatgttttataaa 309 Y T K Q Y E F C T K I R D I D N H V T Y L R D D M F Y K 12882 gaaaacatggaacgttattactacaatccaagcaatttacattttgacaatgcttactctaaaaattacitggttgataitgat 337 E N M E R Y Y Y N P S N L H F D N A Y S K N Y V 7 D N D 12798 agatatttatatttagatatgaataaaattataaaatttcatataaaaaatgaaatgaagaaaaatatgagtgagtttgaaaga 365 R Y L Y L D M N K I I K F H I K N E M K K N M S E F E R 12714 aaagaaaaaatatacgaagataactatatagagaatacgaaaaagtatctaatgaaacaatatggcttataa 12643 393 K E K I Y E D N Y I E N T K K Y L M K Q Y G L * 44AHJDORFOO6 WO 00/32825 PCT/IB99/02040 275 803 atggcacaacaatctacaaaaaatgaaactgcacttttagtagcaaagtcagctaaatcagcgttacaagattttaatcatgat 1 M A Q Q S T K N E T A L L V A K S A K S A L Q D F N H D 887 tattcaaaatcttggacatttggcgacaaatgggataattcaaatacaatgttcgaaacatttgtaaataaatatttattccct 29 Y S K S W T F G D K W D N S N T M F E T F V N K Y L F P 971 aagattaatgagactttattaatcgatattgcattaggtaatCgttttaattggttagctaaagagcaagattttattggacaa 57 K I N E T L L I D I A L G N R F N W L A K E Q D F I G Q 1055 tatagtgaagaatacgtgattatggacacagtaccaattaacatggacttatctaaaaatgaggaattaatgttgaaacgtaat 85 Y S E E Y V I M D T V P I N M D L S K N E E L M L K R N 1139 tatccacgtatggcaactaagttatatggtaacggaattgtgaagaaacaaaaattcacattaaacaacaatgatacacgtttc 113 Y P R M A T K L Y G N G I V K K Q K F T L N N N D T R F 1223 aatttccaaacattagcagacgcaactaattacgctttaggtgtatacaaaaagaaaatttctgatattaatgtattagaagaa 141 N F Q T L A D A T N Y A L G V Y K K K I S D I N V L E E 1307 aaagaaatgcgtgcaatgttagttgattactcattgaatcaattatccgaaacaaatgtacgtaaagcaacatcaaaagaagat 169 K E M R A M L V D Y S L N Q L S E T N V R K A T S K E D 1391 ttagcaagcaaagtttttgaagcaatcctaaacttacaaaacaacagtgctaaatataatgaagtacatcgtgcatcaggtggt 197 L A S K V F E A I L N L Q N N S A K Y N E V H R A S G G 1475 gcaattggacaatatacaactgtatcaaaattaaaagatattgtgattttaacaacagattcattaaaatcttatcttttagat 225 A I G Q Y T T V S K L K D I V I L T T D S L K S Y L L D 1559 actaagattgcaaacacattccagattgcaggcattgatttcacagatcacgttattagttttgacgacttaggtggcgtgttt 253 T K I A N T F Q I A G I D F T D H V I S F D D L G G V F 1643 aaagtaacaaaagaatttaagttacaaaaccaagattcaattgactttttacgtgcgtatggagattatcaatcacaattagga 281 K V T K E F K L Q N Q D S I D F L R A Y G D Y Q S Q L G 1727 gatacaattccagttggtgctgtatttacttatgatgtatctaaacttaaagagtttactggcaacgttgaagaaattaaacca 309 D T I P V G A V F T Y D V S K L K E F T G N V E E I K P 1811 aaatcagatttatatgcgtttattttggatattaattcaattaaatataaacgttacacaaaaggtatgttaaaaccaccattc 337 K S D L Y A F I L D I N S I K Y K R Y T K G M L K P P F 1895 cataaccctgaatttgatgaagttacacactggattcattactattcatttaaagccattagtccattctttaataaaatttta 365 H N P E F D E V T H W I H Y Y S F K A I S P F F N K I L 1979 attactgaccaagatgtaaatccaaaaccagaggaagaattacaagaataa 2029 393 I T D Q D V N P K P E E E L Q E * 4 4AHJDORFO 07 2044 atgaacaacgataaaagaggtttaaacgttgagttatcaaaggaaatcagcaaaagagttgttgaacatcgcaacagatttaaa 1 M N N D K R G L N V E L S K E I S K R V V E H R N R F K 2128 cgtcttatgtttaatcgttatttggaatttttaccgctactaatcaactataccaatcgtgatacggttggtatagattttatt 29 R L M F N R Y L E F L P L L I N Y T N R D T V G I D F I 2212 cagttagaatcagctttaagacaaaacattaatgtagttgttggtgaagctagaaataagcaaattatgattcttggttatgta 57 Q L E S A L R Q N I N V V V G E A R N K Q I M I L G Y V 2296 aataacacttactttaatcaagcaccaaatttttcatcaaactttaatttccaatttcaaaaacgattaactaaagaagatata 85 N N T Y F N Q A P N F S S N F N F Q F Q K R L T K E D I 2380 tattttattgtacctgactatttaatacctgatgattgtctacaaattcataagctatatgataactgtatgagtggtaacttt 113 Y F I V P D Y L I P D D C L Q I H K L Y D N C M S G N F 2464 gttgtcatgcaaaataaaccaattcaatataatagtgatatagaaattatagaacattatactgatgaattagcagaagttgct 141 V V M Q N K P I Q Y N S D I E I I E H Y T D E L A E V A 2548 ttatctcgcttttctttaatcatgcaagcaaaatttagcaagatatttaaatcagaaattaatgacgagtcaatcaatcaactt 169 L S R F S L I M Q A K F S K I F K S E I N D E S I N Q L 2632 gtgtccgaaatatataacggtgcaccatttgttaaaatgtcacctatgtttaatgcagatgacgatatcattgatttaacaagt 197 V S E I Y N G A P F V K M S P M F N A D D D I I D L T S 2716 aatagcgtaatcccagcattaactgaaatgaaacgggaatatcaaaacaaaattagtgaattaagtaactatttaggcattaat 225 N S V I P A L T E M K R E Y Q N K I S E L S N Y L G I N 2800 tcattagccgttgataaagaaagcggtgtttcagacgaagaggcaaaaagtaatcgtggatttaccacatcaaacagtaatatc 253 S L A V D K E S G V S D E E A K S N R G F T T S N S N I 2884 tatttaaaaggtcgtgaaccaattacgtttttatcaaagcgttatggtttagatattaaaccgtattacgatgatgaaacaacg 281 Y L K G R E P I T F L S K R Y G L D I K P Y Y D D E T T 2968 tctaaaatatcaatggtagacacactttttaaagatgaaagcagtgatataaatggctag 3027 309 S K I S M V D T L F K D E S S D I N G * 44AHJDORFOO8 3020 atggctagatacacaatgactttatacgatttcattaaatcagaattgattaaaaaaggtttcaatgaatttgtaaatgataat 1 M A R Y T M T L Y D F I K S E L I K K G F N E F V N D N 3104 aaattaacgttttatgatgatgaatttcaattcatgcaaaaaatgctgaagttcgacaaagacgttttagctatcgttaatgaa 29 K L T F Y D D E F Q F M Q K M L K F D K D V L A I V N E 3188 aaagtatttaaaggtttttcattgaaagatgaattatcagatttactttttaaaaaatcatttacgattcattttttagataga 57 K V F K G F S L K D E L S D L L F K K S F T I H F L D R 3272 gaaatcaacagacaaacagttgaagcatttggcatgcaagtgattactgtatgtattacacatgaggattatttaaatgtggtt 85 E I N R Q T V E A F G M Q V I T V C I T H E D Y L N V V 3356 tattcatcaagtgaagttgaaaaatacttacaatcacaaggcttcacagaacacaatgaagatacaacaagtaacactgatgaa 113 Y S S S E V E K Y L Q S Q G F T E H N E D T T S N T D E 3440 acatcgaatcaaaatgctacatctttagacaattcaactggcatgactgcaaacagaaacgcttatgtgtcattaccacaaagt 141 T S N Q N A T S L D N S T G M T A N R N A Y V S L P Q S 3524 gaggttaacattgatgttgataatacaacgttacgattcgctgataataatacgattgataacggtaaaactgtgaataaatcg 169 E V N ID V D NT T L R FAD N N TI DN G K TV N-LK S 3608 agtaacgaaagtaatcaaaacgcaaaacgtaatcaaaatcaaaaaggtaatgcaaaaggtacacaattcactaagcagtattta 197 S N E S N Q N A K R N Q N Q K G N A K G T Q F T K Q Y L 3692 attgataatattgataaagcgtacgatttaagaaagaaaattttaaatgaatttgataaaaaatgttttttacaaatttggtag 3775 225 I D N I D K A Y D L R K K I L N E F D K K C F L Q I W * 44AHJDORFOO9 WO 00/32825 PCT/IB99/02040 276 5744 atgaaatcacaacaacaagcaaaagaatggatatataagcatgagggggcaggtgttgactttgatggtgcatatggatttcaa 1 M K S Q Q Q A K E W I Y K H E G A G V D F D G A Y G F Q 5828 tgtatggacttatcagttgcttatgtgtattacattactgacggtaaagttcgcatgtggggtaatgctaaagacgcgataaat 29 C M D L S V A Y V Y Y I T D G K V R M W G N A K D A I N 5912 aatgactttaaaggtttagcgacggtgtataaaaatacaccgagctttaaacctcaattaggggacgttgctgtatatacaaat 57 N D F K G L A T V Y K N T P S F K P Q L G D V A V Y T N 5996 ggacaatatggacatattcaatgtgtgttaagtggaaatcttgattattatacatgcttagaacaaaactggttaggcggcggt 85 G Q Y G H I Q C V L S G N L D Y Y T C L E Q N W L G G G 6080 tttgacggttgggaaaaagcaaccattagaacacattattatgacggtgtaactcactttattagacctaaattttcaggtagt 113 F D G W E K A T I R T H Y Y D G V T H F I R P K F S G S 6164 aatagcaaagcattagaaacatcaaaagtaaatacatttggaaaatggaaacgaaaccaatacggcacatattatagaaatgaa 141 N S K A L E T S K V N T F G K W K R N Q Y G T Y Y R N E 6248 aatggtacatttacatgtggttttttaccaatatttgcacgtgtcggtagtccaaaattatcagaacctaatggctattggttc 169 N G T F T C G F L P I F A R V G S P K L S E P N G Y W F 6332 caaccaaacggttatacaccatataacgaagtttgtttatcagatggttacgtatggattggttataactggcaaggcacacgt 197 Q P N G Y T P Y N E V C L S D G Y V W I G Y N W Q G T R 6416 tattatttaccagtgcgccaatggaatggaaaaacaggtaatagttacagtgttggtattccttggggggtgttctcataa 6496 225 Y Y L P V R Q W N G K T G N S Y S V G I P W G V F S * 44AHJDORFO1O 14420 ttggttagacatacgtctgaaatggatagatggaaaaaagaaagagaagctagaaaagagcaagaaaaagatttatttttaaat 1 L V R H T S E M D R W K K E R E A R K E Q E K D L F L N 14336 gattttagtaatgttaattttaaatttgatgataaagatttacaagaggcgtacattgacacatggaaacattttgcacatctg 29 D F S N V N F K F D D K D L Q E A Y I D T W K H F A H L 14252 ccctattttcctaaagaaagaaacgtatcatatgtaaatgctgtatcattggtaagaggttcaagacataaaaaattaaattat 57 P Y F P K E R N V S Y V N A V S L V R G S R H K K L N Y 14168 attcttgaaatatataaccgtaatgatgattctaataataaaaacgctaaaaagcataaatacgctttatataatttacaagct 85 I L E I Y N R N D D S N N K N A K K H K Y A L Y N L Q A 14084 aaaaataataattcttcaatgtataaatatattaaagaaatcgatactttatataaagaaattggtaaatcagatagaccagtg 113 K N N N S S M Y K Y I K E I D T L Y K E I G K S D R P V 14000 acaaatattgatgatgaagatgtgaggtataactttttatattatgcaacatttgacgaataa 13938 141 T N I D D E D V R Y N F L Y Y A T F D E * 44AHJDORFO11 15593 atgacaaacgtaaaagatattttatcaagacaccaaaacacattagcgagatttgaatttgaggaaaaagaaagagaatttatc 1 M T N V K D I L S R H Q N T L A R F E F E E K E R E F I 15509 aaactatcagaattagtagaaaaatacggtatgaaaaaagagtatatcgttagagcattattcacaaacaaagaatcaaaattc 29 K L S E L V E K Y G M K K E Y I V R A L F T N K E S K F 15425 ggtgaacaaggtgttatcgtcactgatgactataacgtaaacttaccgaaccacttaacagaattaattaaagaaatgagagca 57 G E Q G V I V T D D Y N V N L P N H L T E L I K E M R A 15341 gatgaggacgttgttgacattatcaatgctggagaagttcaattcacaatttatgaatatgaaaacaaaaaaggtcaaaaaggt 85 D E D V V D I I N A G E V Q F T I Y E Y E N K K G Q K G 15257 tactcaatcaattttggtcaagtatcattttaa 15225 113 Y S I N F G Q V S F * 44AHJDORF012 8391 atgaacgaagtaaaattcagatttacagactcagaagcgtttcacatgtttatatacgctggggatttaaaattactctacttt 1 M N E V K F R F T D S E A F H M F I Y A G D L K L L Y F 8475 ttatttgtattaatgttcgttgatattattacaggtatttcaaaagcaattaaaaataataacttatggtcaaaaaaatcaatg 29 L F V L M F V D I I T G I S K A I K N N N L W S K K S M 8559 agaggattttctaaaaaattattgatattctgtattatcattttagcaaacatcattgaccagattttacaattaaaaggtggt 57 R G F S K K L L I F C I I I L A N I I D Q I L Q L K G G 8643 ctactcatgattacaatattttattatattgcaaatgagggactttctattgtagaaaattgtgcagaaatggacgtattagta 85 L L M I T I F Y Y I A N E G L S I V E N C A E M D V L V 8727 ccagaacaaattaaagataaattaagagtcattaaaaatgatactgaaaagagtgataacaatgaacgatcaagagaagataga 113 P E Q I K D K L R V I K N D T E K S D N N E R S R E D R 8811 taa 8813 141 * 44AHJDORF013 14996 atgaaaattaaaactacttttagattaaataatttaatttattaccttttaacaaatagagattattataatgataaatttgaa 1 M K I K T T F R L N N L I Y Y L L T N R D Y Y N D K F E 14912 aaatttacttcatctaataaaaaatgtatagtaaaaataaatatgggtgatgtgtatattgagtttgacaaacaatatgatgat 29 K F T S S N K K C I V K I N M G D V Y I E F D K Q Y D D 14828 tttgaaattgaaaaagagttatttacgttagatatcgacattgatattaaaaaacatgtttttaatatacttgtattttattat 57 F E I E K E L F T L D I D I D I K K H V F N I L V F Y Y 14744 agaaattatttaagtaatgaattaataagagaaattttattaaacgttacaattgacgacgtattatcaaattttgataaacct 85 R N Y L S N E L I R E I L L N V T I D D V L S N F D K P 14660 cttgaaagcgaattaatgattatttatcaaaacaaagtcatatacgataatgggaaagtgattgaccatgaataa 14586 113 L E S E L M I I Y Q N K V I Y D N G K V I D H E * 44AHJDORF113 199 atgacagaatttgatgaaatcgtaaaaccagacgacaaagaagaaacttcagaatcaactgaagaaaatttagaatcaactgaa 1 M T E F D E I V K P D D K E E T S E S T E E'N L E S T E. 283 gaaacttcagaatcaactgaagaatcaactgaagaatcaactgaagaatcaactgaagataaaacagtagaaacaatcg2Agaa 29 E T S E S T E E S T E E S T E E S T E D K T V E T-I E E 367 gaaaatgaaaacaaattagaacctactacaacagatgaagatagttcgaaatttgaccctgttgtattagaacaacgtattgct 57 E N E N K L E P T T T D E D S S K F D P V V L E Q R I A 451 tcattagaacaacaagtgactacttttttatcttcacaaatgcaacaaccacaacaagtacaacaaacacaatcagatgtaaca 85 S L E Q Q V T T F L S S Q M Q Q P Q Q V Q Q T Q S D V T 535 gaatcaaacaaagaagataacgactattcagatgaagaactagttgataagttagatttagattag 600 WO 00/32825 PCT/IB99/02040 277 113 E S N K E D N D Y S D E E L V D K L D L D * 44AHJDORF114 16172 atggttaatgttgataatgcaccagaagaaaaaggacaagcctatactgaaatgttgcaactattcaataaactgattcaatgg 1 M V N V D N A P E E K G Q A Y T E M L Q L F N K L I Q W 16088 aatccagcttatacatttgacaatgcaattaacttattatcggcttgccaacaactattattaaactataatagttctgttgtt 29 N P A Y T F D N A I N L L S A C Q Q L L L N Y N S S V V 16004 caattcttaaatgatgaactaaacaacgaaactaaaccagaatcaatattgtcttatattgctggtgatgacccaatagaacaa 57 Q F L N D E L N N E T K P E S I L S Y I A G D D P I E Q 15920 tggaatatgcataaaggattttatgaaacgtataacgtttacgttttttag 15870 85 W N M H K G F Y E T Y N V Y V F * 44AHJDORF014 6243 atgaaaatggtacatttacatgtggttttttaccaatatttgcacgtgtcggtagtccaaaattatcagaacctaatggctatt 1 M K M V H L H V V F Y Q Y L H V S V V Q N Y Q N L M A I 6327 ggttccaaccaaacggttatacaccatataacgaagtttgtttatcagatggttacgtatggattggttataactggcaaggca 29 G S N Q T V I H H I T K F V Y Q M V T Y G L V I T G K A 6411 cacgttattatttaccagtgcgccaatggaatggaaaaacaggtaatagttacagtgttggtattccttggggggtgtttcat 57 H V I I Y Q C A N G M E K Q V I V T V L V F L G G C S H 6495 aatgggtattttagcctttttctttga 6521 85 N G Y F S L F L * 44AHJDORF015 15403 gtgacgataacaccttgttcaccgaattttgattctttgtttgtgaataatgctctaacgatatactcttttttcataccgtat 1 V T I T P C S P N F D S L F V N N A L T I Y S F F I P Y 15487 ttttctactaattctgatagtttgataaattctctttctttttcctcaaattcaaatctcgctaatgtgttttggtgtcttgat 29 F S T N S D S L I N S L S F S S N S N L A N V F W C L D 15571 aaaatatcttttacgtttgtcattttatttctcctcttatttaaattatttgctttctgcaattgcgatttgtag 15645 57 K I S F T F V I L F L L L F K L F A F C N C D L * 44AHJDORF016 15852 atgaaagttgacgacattgttaccttacgtgtcaaaggttatatacttcattacttagatgatgataatgaatacattgaggaa 1 M K V D D I V T L R V K G Y I L H Y L D D D N E Y I E E 15768 tttttaccacttcacgagtatcatttaaccaaaacacaagcaaaagaattattaccagacacatgtaaactattgtccactaca 29 F L P L H E Y H L T K T Q A K E L L P D T C K L L S T T 15684 cgcacaacgaaaacaattcaagtttattacaatgatttactacaaatcgcaattgcagaaagcaaataa 15616 57 R T T K T I Q V Y Y N D L L Q I A I A E S K * 44AHJDORF017 10757 atggaaagattaaaattgcttctgctggtataccgaaaaacgcctttgatacaagcgtcgattttgaaacctttgtacgtgaac 1 M E R L K L L L L V Y R K T P L I Q A S I L K P L Y V N 10673 aattctttgacggtgccattattgaaaacaataaaagtatctataatgagcaaggtacaatatcgatatatccgtctaaaactg 29 N S L T V P L L K T I K V S I M S K V Q Y R Y I R L K L 10589 aaattgtatgtggtaatgtatatgatgaatattttactgatgaacttaatatga 10536 57 K L Y V V M Y M M N I L L M N L I * 44AHJDORF018 1098 atgttaattggtactgtgtccataatcacgtattcttcactatattgtccaataaaatcttgctctttagctaaccaattaaaa 1 M L I G T V S I I T Y S S L Y C P I K S C S L A N Q L K 1014 cgattacctaatgcaatatcgattaataaagtctcattaatcttagggaataaatatttatttacaaatgtttcgaacattgta 29 R L P N A I S I N K V S L I L G N K Y L F T N V S N I V 930 tttgaattatcccatttgtcgccaaatgtccaagattttgaataa 886 57 F E L S H L S P N V Q D F E 44AHJDORF019 9836 atgttacctggtttgtataagtattcttttttgaataaaggtacaccaattgcttttttatatttttctggtaactgtgcatat 1 M L P G L Y K Y S F L N K G T P I A F L Y F S G N C A Y 9752 gtccagttaccaccaatcacacgaccactttttccatttggcttgactgatttaccactaattggtttatggtctccgtcatca 29 V Q L P P I T R P L F P F G L T D L P L I G L W S P S S 9668 tcagtaggattagaactactactcccactatctacttga 9630 57 S V G L E L L L P L ST * 44AHJDORF121 16362 atggaaaatgaaacaaaaaacattgagttgaagcatgtttttcgttttaagaatggaagtttatgtatagcgttatttgataga 1 M E N E T K N I E L K H V F R F K N G S L C I A L F D R 16278 acagaaaatgaaatttcattttatgatgttgacattgatgaaattgaagatttaaatcataattctgttttacgcgtaatttca 29 T E N E I S F Y D V D I D E I E D L N H N S V L R V I S 16194 actttattaggaagtgataataatggttaa 16165 57 T L L G S D N N G 44AHJDORF020 13865 atgtctaaacgattttgttttaccatgtttttgctccttgtaatagtttatgatgtcgtttacagtgttaaatttattcgtcaa 1 M S K R F C F T M F L L L V I V Y D V V Y S V K F I R Q 13949 atgttgcataatataaaaagttatacctcacatcttcatcatcaatatttgtcactggtctatctgatttaccaatttctttat 29 M L H N I K S Y T S H L H H Q Y L S L V Y L I Y Q F L Y 14033 ataaagtatcgatttctttaa 14053 57 I K Y R F L * 44AHJDORF123 614 atgtatgagggaaacaacatgcgttctatgatgggtacatcatatgaagattcaagattaaataaacgaacagaattaaatgaa 1 M Y E G N N M R S M M G T S Y E D S R L N K R T E L N E 698 aacatgtcaattgatacaaataaaagtgaagatagttatggtgtacaaattcattcactttcaaaacaatcatttacaggtgac 29 N M S I D T N K S E D S Y G V Q I H S L S K Q S F T G D 782 gttgaggaggaataa 796 57 V E E E * WO 00/32825 PCT/IB99/02040 278 44AHJDORF021 5816 atgcaccatcaaagtcaacacctgccccctcatgcttatatatccattcttttgcttgttgttgtgatttcatttatatcactc 1 M H H Q S Q H L P P H A Y I S I L L L V V V I S F I S L 5732 ctatttttgatgttttgctacccaaccatattcacgatgttttgtttccgcattaacattactgaagaattctttatattccga 29 L F L M F C Y P T I F T M F C F R I N I T E E F F I F R 5648 tatattagcctctaa 5634 57 Y I S L * 44AHJDORF022 8611 atgtttgctaaaatgataatacagaatatcaataattttttagaaaatcctctcattgatttttttgaccataagttattattt 1 M F A K M I I Q N I N N F L E N P L I D F F D H K L L F 8527 ttaattgcttttgaaatacctgtaataatatcaacgaacattaatacaaataaaaagtag 8468 29 L I A F E I P V I I S T N I N T N K K * 44AHJDORF023 6494 atgagaacaccccccaaggaataccaacactgtaactattacctgtttttccattccattggcgcactggtaaataataacgtg 1 M R T P P K E Y Q H C N Y Y L F F H S I G A L V N N N V 6410 tgccttgccagttataaccaatccatacgtaaccatctgataaacaaacttcgttatatggtgtataaccgtttggttggaacc 29 C L A S Y N Q S I R N H L I N K L R Y M V Y N R L V G T 6326 aatagccattag 6315 57 N S H * 44AHJDORF024 14275 gtgtcaatgtacgcctcttgtaaatctttatcatcaaatttaaaattaacattactaaaatcatttaaaaataaatctttttct 1 V S M Y A S C K S L S S N L K L T L L K S F K N K S F S 14359 tgctcttttctagcttctctttcttttttccatctatccatttcagacgtatgtctaaccaatgttatcaacctccatataaag 29 C S F L A S L S F F H L S I S D V C L T N V I N L H I K 14443 cataaataa 14451 57 H K * 44AHJDORF025 15175 atggaacgtaaatacaaaacggtattattatattgcgatgagattaaaggacattttccacatcaaatctcaatgtttgaagat 1 M E R K Y K T V L L Y C D E I K G H F P H Q I S M F E D 15091 ttatatgacgctaaagttgtatattcatattatgaatataacctgttcactaaaaaatacgcgtatatcatagaatacattaag 29 L Y D A K V V Y S Y Y E Y N L F T K K Y A Y I I E Y I K 15007 gagatataa 14999 57 E I * 44AHJDORF026 14593 atgaataacctattaaacatagccattgttttccttttagcatttttaattacacttatcatacttatgacactgcatatacgc 1 M N L L N I A I V F L L A F L I T L I I L M T L H I R 14509 gtgtcatttggtgttttattcactacattgattatattctatattatctttttaatggttatttatgctttatatggaggttga 14426 29 V S F G V L F T T L I I F Y I I F L M V I Y A L Y G G * 44AHJDORF027 12916 atgattgtctatatccctaattttagtacaaaattcatattgttttgtatatggtacaacgataatatttgtcataaaagtagt 1 M I V Y I P N F S T K F I L F C I W Y N D N I C H K S S 13000 tacattatacatgactttaatatatttatcatcagttttgatatagaagaaatcaccgttttgattgatgtgatttcttaa 13080 29 Y I I H D F N I F I I S F D I E E I T V L I D V I S * 44AHJDORF029 15183 gtgtttaaatggaacgtaaatacaaaacggtattattatattgcgatgagattaaaggacattttccacatcaaatctcaatgt 1 V F K W N V N T K R Y Y Y I A M R L K D I F H I K S Q C 15099 ttgaagatttatatgacgctaaagttgtatattcatattatgaatataacctgttcactaaaaaatacgcgtatatcatag 15019 29 L K I Y M T L K L Y I H I M N I T C S L K N T R I S * 44AHJDORF028 9235 atggaatatatgcacgtccaattgtacctgctttcatattttttgcaaaatctgcattaccttttctttgtacgtcttgtggta 1 M E Y M H V Q L Y L L S Y F L Q N L H Y L F F V R L V V 9151 caaagtggacgatgttacctgcgtcataccaagacggttgtccagcttgttttgattgtgatactaactttcttgctatga 9071 29 Q S G R C Y L R H T K T V V Q L V L I V I L T F L L * 44AHJDORF030 14487 gtgaataaaacaccaaatgacacgcgtatatgcagtgtcataagtatgataagtgtaattaaaaatgctaaaaggaaaacaatg 1 V N K T P N D T R I C S V I S M I S V I K N A K R K T M 14571 gctatgtttaataggttattcatggtcaatcactttcccattatcgtatatgactttgttttgataaataatcattaa 14648 29 A M F N R L F M V N H F P I I V Y D F V L I N N H * 44AHJDORF031 11039 atgatattgtatagttcattgttatcatctaaacggaataagttaaaatgtgaacgtaatgcaggtatgccatataatccattt 1 M I L Y S S L L S S K R N K L K C E R N A G M P Y N P F 11123 aaaacgactttagataacataacctcctcatttgagtatgggtgttcgttgatatcatcagtaatgtga 11191 29 K T T L D N I T S S F E Y G C S L I S S V M * 44AHJDORF135 693 atgaaaacatgtcaattgatacaaataaaagtgaagatagttatggtgtacaaattcattcactttcaaaacaatcttacag 1 M K T C Q L I Q I K V K I V M V Y K F I H F Q N N-.H L Q 777 gtgacgttgaggaggaataataaattatggcacaacaatctacaaaaaatgaaactgcacttttag 842 29 V T L R R N N K L W H N N L Q K M K L H F * 44AHJDORF033 3795 atgccattatttaaccacctctaccaaatttgtaaaaaacattttttatcaaattcatttaaaattttctttcttaaatcgtac 1 M P L F N H L Y Q I C K K H F L S N S F K I F F L K S Y WO 00/32825 PCT/IB99/02040 279 3711 gctttatcaatattatcaattaaatactgcttagtgaattgtgtaccttttgcattacctttttga 3646 29 A L S I L S I K Y C L V N C V P F A L P F * 44AHJDORF032 9455 atggcttgttttgctaaagcgagtagtgaactaccactgtcaccactactaccactgtcagacgaatcactaggtgatccacct 1 M A C F A K A S S E L P L S P L L P L S D E S L G D P P 9371 ttaccgtctaatttaccaccccaagctagaatagtattcgcaccgtctaaaaatggattaccatag 9306 29 L P S N L P P Q A R I V F A P S K N G L P * 44AHJDORF034 14146 atgatgattctaataataaaaacgctaaaaagcataaatacgctttatataatttacaagctaaaaataataattcttcaatgt 1 M M I L I I K T L K S I N T L Y I I Y K L K I I I L Q C 14062 ataaatatattaaagaaatcgatactttatataaagaaattggtaaatcagatagaccagtga 14000 29 I N I L K K S I L Y I K K L V N Q I D Q * 44AHJDORF035 13957 atgcaacatttgacgaataaatttaacactgtaaacgacatcataaactattacaaggagcaaaaacatggtaaaacaaaatcg 1 M Q H L T N K F N T V N D I I N Y Y K E Q K H G K T K S 13873 tttagacatggtaagagattatcaaaatgctgtcaatcatgtcagaaaaaaaatcccagataa 13811 29 F R H G K R L S K C C Q S C Q K K N P R * 44AHJDORF036 10165 gtgtatacaataccacacgtgatggtgcaacatatggtggtacattatagtttgcaactaaaaacgaaccatcttcaaaaactg 1 V Y T I P H V M V Q H M V V H Y S L Q L K T N H L Q K L 10081 ctacaacaacacctgtgtgaccaataccatatgcagttgcttgtaagtatggtggtttactag 10019 29 L Q Q H L C D Q Y H M Q L L V S M V V Y * 44AHJDORF037 14788 atgtcgatatctaacgtaaataactctttttcaatttcaaaatcatcatattgtttgtcaaactcaatatacacatcacccata 1 M S I S N V N N S F S I S K S S Y C L S N S I Y T S P I 14872 tttatttttactatacattttttattagatgaagtaaatttttcaaatttatcattataa 14931 29 F I F T I H F L L D E V N F S N L S L * 44AHJDORF038 3671 gtgtaccttttgcattacctttttgattttgattacgttttgcgttttgattactttcgttactcgatttattcacagttttac 1 V Y L L H Y L F D F D Y V L R F D Y F R Y S I Y S Q F Y 3587 cgttatcaatcgtattattatcagcgaatcgtaacgttgtattatcaacatcaatgttaa 3528 29 R Y Q S Y Y Y Q R I V T L Y Y Q H Q C * 44AHJDORF039 1743 gtgctgtatttacttatgatgtatctaaacttaaagagtttactggcaacgttgaagaaattaaaccaaaatcagatttatatg 1 V L Y L L M M Y L N L K S L L A T L K K L N Q N Q I Y M 1827 cgtttattttggatattaattcaattaaatataaacgttacacaaaaggtatgttaa 1883 29 R L F W I L I Q L N I N V T Q K V C * 44AHJDORF040 9740 gtggtaactggacatatgcacagttaccagaaaaatataaaaaagcaattggtgtacctttattcaaaaaagaatacttataca 1 V V T G H M H S Y Q K N I K K Q L V Y L Y S K K N T Y T 9824 aaccaggtaacatatttcctcaaacgggtaatgcaggacaatgtacagaattaa 9877 29 N Q V T Y F L K R V M Q D N V Q N * 44AHJDORF041 15836 atgtcgtcaactttcattattatatcactcctttctaaaaaacgtaaacgttatacgtttcataaaatcctttatgcatattcc 1 M S S T F I I I S L L S K K R K R Y T F H K I L Y A Y S 15920 attgttctattgggtcatcaccagcaatataagacaatattgattctggtttag 15973 29 I V L L G H H Q Q Y K T I L I L V * 44AHJDORF042 5151 atgcacgaccgtcgtcttttgttaatttatagttttgtgaacctcttgcgcgtaatgcttcaaagtgttcatactcaccaagtt 1 M H D R R L L L I Y S F V N L L R V M L Q S V H T H Q V 5067 ggaagaaaccatataaattatggaaacgttttccaccaccgccgtttgtcatag 5014 29 G R N H I N Y G N V F H H R R L S * 44AHJDORF043 4539 atgcgacttgtaacagttttgcaacaccatcgtgatgtaaccagattttcatttcaccattggattgacgttctaatccgattg 1 M R L V T V L Q H H R D V T R F S F H H W I D V L I R L 4455 ttgtaccatgaccaccctgtacaatacgcatgcttgaaattaagtcaccactag 4402 29 L Y H D H P V Q Y A C L K L S H H * 44AHJDORF044 12917 atgttacctatttacgtgatgatatgttttataaagaaaacatggaacgttattactacaatccaagcaatttacattttgaca 1 M L P I Y V M I C F I K K T W N V I T T I Q A I Y I L T 12833 atgcttactctaaaaattacgtggttgataatgatagatatttatatttag 12783 29 M L T L K I T W L I M I D I Y I * 44AHJDORF149 770 atgattgttttgaaagtgaatgaatttgtacaccataactatcttcacttttatttgtatcaattgacatgttttcatttaatt 1 M I V L K V N E F V H H N Y L H F Y L Y Q L T C F H L I 686 ctgttcgtttatttaatcttgaatcttcatatgatgtacccatcatag 639 29 L F V Y L I L N L H M M Y P S * 44AHJDORF046 4891 atgattatccatttaagttatcatatcaagacggtattaatttcccacgtgataactttaaagagcctgafggtatttgcattt 1 M I I H L S Y H I K T V L I S H V I T L K S L R V-F A F 4975 atacaaatccaaaaacaaaacgtaaatcgttattacttgctatga 5019 29 I Q I Q K Q N V N R Y Y L L * 44AHJDORF047 11911 atgaatgtatgtaagttgttcaggtgtgagttttgcaaaacatttcacagcatagtcataggcttcactatcattcatatcatt 1 M N V C K L F R C E F C K T F H S I V I G F T I I H I I WO 00/32825 PCT/IB99/02040 280 11995 atctttatcaaaaatcgtataattaaaatctgttttaagttgtga 12039 29 I F I K N R I I K I C F K L 44AHJDORF045 10655 atggcaccgtcaaagaattgttcacgtacaaaggtttcaaaatcgacgcttgtatcaaaggcgtttttcggtataccagcagaa 1 M A P S K N C S R T K V S K S T L V S K A F F G I P A E 10739 gcaattttaatctttccattcacttcatatgcatatttcttatga 10783 29 A I L I F P F T S Y A Y F L * 44AHJDORF048 15340 atgaggacgttgttgacattatcaatgctggagaagttcaattcacaatttatgaatatgaaaacaaaaaaggtcaaaaaggtt 1 M R T L L T L S M L E K F N S Q F M N M K T K K V K K V 15256 actcaatcaattttggtcaagtatcattttaatacaatttcatag 15212 29 T Q S I L V K Y H F N T I S * 44AHJDORF049 5784 atgagggggcaggtgttgactttgatggtgcatatggatttcaatgtatggacttatcagttgcttatgtgtattacattactg 1 M R G Q V L T L M V H M D F N V W T Y Q L L M C I T L L 5868 acggtaaagttcgcatgtggggtaatgctaaagacgcgataa 5909 29 T V K F A C G V M L K T R * 44AHJDORF050 13158 gtgtgttacgtttttcattcacgtaatcgtttcgtcgcatttctaaaaaaatgtttttgtaaagtcttgatgtattcattttat 1 V C Y V F H S R N R F V A F L K K C F C K V L M Y S F Y 13242 gcttttgtaataaattgtatatatttaaattggataatatag 13283 29 A F V I N C I Y L N W I I * 44AHJDORF051 11066 atgataacaatgaactatacaatatcattaacggttacaaaaacactgaacgtaatatattattctctacatttgtcacatcac 1 M I T M N Y T I S L T V T K T L N V I Y Y S L H L S H H 10982 gttcattgtataacttattggttcctttccaatacttaa 10944 29 V H C I T Y W F L S N T * 44AHJDORF052 14338 atgattttagtaatgttaattttaaatttgatgataaagatttacaagaggcgtacattgacacatggaaacattttgcacatc 1 M I L V M L I L N L M I K I Y K R R T L T H G N I L H I 14254 tgccctattttcctaaagaaagaaacgtatcatatgtaa 14216 29 C P I F L K K E T Y H M 44AHJDORF053 3348 atgtggtttattcatcaagtgaagttgaaaaatacttacaatcacaaggcttcacagaacacaatgaagatacaacaagtaaca 1 M W F I H Q V K L K N T Y N H K A S Q N T M K I Q Q V T 3432 ctgatgaaacatcgaatcaaaatgctacatctttag 3467 29 L M K H R I K M L HL * 44AHJDORF054 7551 atgactggaatggaaatacgatgttactcgacgctggtaagatttcacaaaaaactggtgttaagttacgtacaaaatcaatta 1 M T G M E I R C Y S T L V R F H K K L V L S Y V Q N Q L 7635 ttggttatcataatgaagttcgagtatatccagtag 7670 29 L V I I M K F E Y I Q * 44AHJDORFOSS 15705 atgtgtctggtaataattcttttgcttgtgttttggttaaatgatactcgtgaagtggtaaaaattcctcaatgtattcattat 1 M C L V I I L L L V F W L N D T R E V V K I P Q C I H Y 15789 catcatctaagtaatgaagtatataacctttga 15821 29 H H L S N E V Y N L * 44AHJDORF056 5512 gtgagtattacattacaggtaaccaaatggaattatttagagacgcgccagaagaaattaaaaaagtgggtgcatggttacgtg 1 V S I T L Q V T K W N Y L E T R Q K K L K K W V H G Y V 5596 tgtcaagtggtaacgcagtcggtgaagtaa 5625 29 C Q V V T Q S V K * 44AHJDORF057 10121 atgtaccaccatatgttgcaccatcacgtgtggtattgtatacactcattaatggcgtaccaaataatgctggtgataatattg 1 M Y H H M L H H H V W Y C I H S L M A Y Q I M L V I I *L 10205 tattctttagtggtattgcttaattaa 10231 29 Y S L V V L L N * 44AHJDORF058 10767 atgcatatttcttatgattcagtacaaacatcttatctatctgttcgttttcaatatcccatttacctaaggctatcgggtcga 1 M H I S Y D S V Q T S Y L S V R F Q Y P I Y L R L S G R 10851 ataaactggggttcaataagggtttaa 10877 29 I N W G S I R V 44AHJDORF164 702 atgttttcatttaattctgttcgtttatttaatcttgaatcttcatatgatgtacccatcatagaacgcatgttgtttccctca 1 M F S F N S V R L F N L E S S Y D V P I I E R M L F P S 618 tacatgtttaaattcctcctaatctaa 592 29 Y M F K F L L I * 44AHJDORF059 8360 atggattttgtaacattggattacctgaaccgtcattatgccaaaatcttacaccagattctaaaattgcttttaattgttcca 1 M D F V T L D Y L N R H Y A K I L H Q I L K L L h I V P 8276 ttaacatggggtcgatgtcacgtatag 8250 29 L T W G R C H V * 44AHJDORF060 6257 atgtaccattttcatttctataatatgtgccgtattggtttcgtttccattttccaaatgtatttacttttgatgtttctaatg 1 M Y H F H F Y N M C R I G F V S I F Q M Y L L L M F L M WO 00/32825 PCT/IB99/02040 281 6173 ctttgctattactacctgaaaatttag 6147 29 L C Y Y Y L K I * 44AHJDORF061 15551 atgtgttttggtgtcttgataaaatatcttttacgtttgtcattttatttctcctcttatttaaattatttgctttctgcaatt 1 M C F G V L I K Y L L R L S F Y F S S Y L N Y L L S A I 15635 gcgatttgtagtaaatcattgtaa 15658 29 A I C S K S L * 44AHJDORF062 4285 gtggtattcgcaacgcagttaaccaatctattaatattgataaagaaacaaatcacatgtactctacacaatccgattctcaaa 1 V V F A T Q L T N L L I L I K K Q I T C T L H N P I L K 4369 aacctgaaggtttttggataa 4389 29 N L K V F G * 44AHJDORF063 9487 atgcgtcttgtattttttttaataattcttgcatggcttgttttgctaaagcgagtagtgaactaccactgtcaccactactac 1 M R L V F F L I I L A W L V L L K R V V N Y H C H H Y Y 9403 cactgtcagacgaatcactag 9383 29 H C Q T N H * 44AHJDORF065 5029 gtggtggaaaacgtttccataatttatatggtttcttccaacttggtgagtatgaacactttgaagcattacgcgcaagaggtt 1 V V E N V S I I Y M V S S N L V S M N T L K H Y A Q E V 5113 cacaaaactataaattaa 5130 29 H K T I N * 44AHJDORF064 2609 atgacgagtcaatcaatcaacttgtgtccgaaatatataacggtgcaccatttgttaaaatgtcacctatgtttaatgcagatg 1 M T S Q S I N L C P K Y I T V H H L L K C H L C L M Q M 2693 acgatatcattgatttaa 2710 29 T I S L I * 44AHJDORF066 10481 atgatattctttatattgaaagtgacatcggttcattttcacttaacgacttatttccagttgaacgttcagtacataacaaat 1 M I F F I L K V T S V H F H L T T Y F Q L N V Q Y I T N 10397 ctgatttgcatatattaa 10380 29 L I C I Y * WO 00/32825 PCT/IB99/02040 282 Table 19 Sequence similarities between ORFs 44AHJD and public databases Phage: 44AHJD Database: nr Query= sid|110871|lanI44AHJDORF001 Phage 44AHJD ORF110342-126271-1 (761 letters) gil118848|sp|P19894|DPOL_BPM2 DNA POLYMERASE >gij76896jpirjJQ0 ... 55 le gil1072656|pirl IS51275 DNA polymerase - phage CP-1 >gi1836593|e ... 53 6e-06 gil1429230|embICAA676491 (X99260) DNA polymerase (Bacteriophage... 49 le-04 gil1572479|emb1CAA657121 (X96987) DNA polymerase (Bacteriophage... 46 0.001 giI118851|spIP069SOIDPOLBPPZA DNA POLYMERASE (EARLY PROTEIN GP... 45 0.002 gil2435429 (AF012250) unassigned reading frame (possible DNA po... 45 0.002 gil10844871pirl lS41618 DNA polymerase - slime mold (Physarum po... 45 0.002 gil4877819|gbIAAD31446.1 (AF133505) DNA polymerase [Neurospora... 44 0.004 gil461962|spIP33537IDPOMNEUCR PROBABLE DNA POLYMERASE >gil2833... 44 0.004 gil2499511jspQ12471|6P22_YEAST 6-PHOSPHOFRUCTO-2-KINASE 2 (PHO ... 41 0.041 gil22583751gblAAD11909.1| (AF007261) transcription initiation f ... 40 0.070 gill734lembICAA374501 (X53370) DNA polymerase (AA 1-575) [Bact. ... 39 0.092 Query= sidjllO872jlanI44AHJDORFOO2 Phage 44AHJD ORF13789-573213 (647 letters) gil1352731spIP276221TAGCBACSU TEICHOIC ACID BIOSYNTHESIS PROTE .. . 112 7e-24 gi1142847 (M64050) ONase inhibitor (Bacillus subtilis] 52 le-OS gi14038407 (AF103943) factor C protein precursor [Streptomyces . .. 39 0.10 Query= sid11O873lan44AHJDORFOO3 Phage 44AHJD ORF16626-838912 (587 letters) giJ1381231spIP043311V9_BPPH2 TAIL PROTEIN (LATE PROTEIN GP9) > ... 92 8e-18 gi11381241spIP075341VG9_BPPZA TAIL PROTEIN (LATE PROTEIN GP9) >. ... 82 le-14 gill429238lembiCAA676571 (X99260) tail protein (Bacteriophage B ... 78 2e-13 giJ215339 (M12456) p9 tail protein (Bacteriophage phi-29] >giJ2 ... 71 2e-11 giI1181968lembjCAA87738.lI (Z47794) tail protein (Bacteriophage ... 54 3e-06 giJll897embICAA8774O.11 (547794) tail protein [Bacteriophage ... 42 0.010 Query= sid11O875lan44AHJDORFOO5 Phage 44AHJD ORF112643-138901-1 (415 letters) giJ 3845203 (AE001399) GAF domain protein (cyclic nt signal tran. ... 52 6e-06 gil37588431emb1CAB11128.11 (E98551) predicted using hexExon; MA ... 49 5e-05 giJ3845297 (AE001421) hypothetical protein [Plasmodium falciparum] 48 le-04 gil4493936lembICAB38972.11 (AL034556) predicted using hexExon; . .. 47 2e-04 giJ3845165 (AE001390) hypothetical protein [Plasmodium falciparum) 46 6e-04 Query= sidi1lO877IlanI44AHJDORFOO7 Phage 44AHJD ORF12044-302711 (327 letters) gil11B1960lembICAA87731.11 (Z47794) connector protein (Bacterio. ... 46 Se-04 gill429239lembICAA676581 (X99260) upper collar protein (Bacteri. ... 45 8e-04 gil379151spIP075351VG1_BPPZA UPPER COLLAR PROTEIN (CONNECTOR . . . 44 0.002 giJ1379141spIP04332VG10_BPPH2 UPPER COLLAR PROTEIN (CONNECTOR .. . 41 0.009 Query= sidI110878lan|44AHJDORF008 Phage 44AHJD ORF13020-377512 (251 letters) gil49824681gbjAAl30963.21 (AF118151) SNF1/AMP-activated kinase . .. 52 3e-06 giJl7300771spIPl816OIKYK1_DICDI NON-RECEPTOR TYROSINE KINASE SP. ... 46 2e-04 gil3758855lembiCAllll4O.lj (Z98551) predicted using hexExon; MA ... 46 2e-04 gil585793|spIP2138REBAYEAST DNA-BINDING PROTEIN REB1 ( .BP) > ... 46 3e-04 gil172372 (M58728) DNA-binding protein (Saccharomyces cerevisiae] 46 3e-04 gi2952545 (AF051898) coronin binding protein (Dictyostelium di... 45 6e-04 gil535260lembICAA82996_ (E30339) STARP antigen (Plasmodium reic ... 45 7e-04 gil1429240embiCAA676591 (X99260) lower collar protein Bacteri ... 44 0.001 WO 00/32825 PCT/IB99/02040 283 Query= sidll0879jlanI44AHJDORF009 Phage 44AHJD ORF15744-649612 (250 letters) gil2764981lemb|CAA69021.1| (Y07739) N-acetylmuramoyl-L-alanine ... 180 le-44 giI1136751spIP24556|ALYS_STAAU AUTOLYSIN (N-ACETYLMURAMOYL-L-AL ... 118 6e-26 gil1763243 (U72397) amidase (bacteriophage 80 alpha] 118 6e-26 gil4574237|gb|AAD23962.11AF106851_1 (AF106851) LytN [Staphyloco... 84 9e-16 gil3767593|dbj|BAA33856.1| (AB015195) LytN (Staphylococcus aureus] 84 9e-16 gil2764983|emb|CAA69022.1| (Y07740) cell wall hydrolase Ply187 ... 77 2e-13 gi|3287732|splO05156|ALE1_STACP GLYCYL-GLYCINE ENDOPEPTIDASE AL... 73 2e-12 gil799261pir||A25881 lysostaphin precursor - Staphylococcus sim ... 69 3e-11 gil126496|spIP10548lLSTPSTAST LYSOSTAPHIN PRECURSOR (GLYCYL-GL... 69 3e-11 gil32879671sp|P10547ILSTPSTASI LYSOSTAPHIN PRECURSOR (GLYCYL-G ... 69 3e-11 gi|3341932|dbjlBAA31898.1I (AB009866) amidase (peptidoglycan hy... 68 6e-11 Query= sid|110882|lan|44AHJDORF012 Phage 44AHJD ORF18391-881313 (140 letters) gi|1405281sp|P24811|YQXHBACSU HYPOTHETICAL 15.7 KD PROTEIN IN ... 80 6e-15 gil4126631IdbjjBAA3665l.lj (AB016282) ORF45 (bacteriophage phi-... 76 le-13 gil141088|spjP26835|YNGD_CLOPE HYPOTHETICAL 14.9 KD PROTEIN IN ... 61 4e-09 gi12293160 (AF008220) YtkC [Bacillus subtilis] >gil2635548|emb| ... 36 0.099 gill181973|embICAA87743.11 (Z47794) holin protein [Bacteriophag ... 31 3.3 WO 00/32825 PCT/IB99/02040 284 Table 20 Homolgies between phage 44 AHJD ORFs and proteins in public databases Query= pt|110871 44AHJDORFOO1 Phage 44AHJD ORF 110342-126271-1 1 (761 letters) >gil118848|spjP19894|DPOLBPM2 DNA POLYMERASE >gij76896|pir||JQOi61 DNA-directed DNA polymerase (EC 2.7.7.7) - phage M2 >gil215509 (M33144) DNA polymerase (Bacteriophage M2] Length = 572 Score = 55.4 bits (131), Expect = ic-06 Identities = 96/426 (22%), Positives = 159/426 (36%), Gaps = 88/426 (20%) Query: 229 KLTPEQLTYIHNDVIILGMCHIHYSDIFPNFDYNKLTFSLNIMESYLNNEMTR-----FQ 283 ++TPE+ YI ND+ I+ DI +++T + ++ + + T+ F Sbjct: 154 EITPEEYEYIKNDIEIIARA----LDIQFKQGLDRMTAGSDSLKGFKDILSTKKFNKVFP 209 Query: 284 LLNQYQDIKISYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYP 343 L+ D +I + YRGG N KY K I E D+NS YP Sbjct: 210 KLSLPMDKEI----------------RKAYRGGFTWLNDKYKEKEIGEGMV-FDVNSLYP 252 Query: 344 YVMYHEKIPTWLYFYEHYSEPTLIPTFLDDDNYFSLYKIDKDVFNDDLLIKIKSRVLRQM 403 MY +P Y P + + D + LY I + F +L K + + Sbjct: 253 SQMYSRPLP--------YGAPIVFQGKYEKDEQYPLY-IQRIRFEFEL----KEGYIPTI 299 Query: 404 XXXXXXXXXXXXXXXXXXLRMIQ-DITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIK 462 + ++ +T +D I+ + + +Y EY F + Sbjct: 300 QIKKNPFFKGNEYLKNSGVEPVELYLTNVDLELIQEH-YELYNVEYIDGFK------FRE 352 Query: 463 TQGKLKNKINMTSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYG ----------- IPAL 511 G K+ I+ + H + L+K++LN LYG +P L Sbjct: 353 KTGLFKDFIDKWTYVKTH --------- -EEGAKKQLAKLMLNSLYGKFASNPDVTGKVPYL 403 Query: 512 RSHFNL-FRLDDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNF 570 + +L FR+ D YK+ + F+T+ + + + Q D Sbjct: 404 KDDGSLGFRVGDEE--------YKDPVYTPM-GVFITAWARFTTITAAQACY-----DRI 449 Query: 571 IYCDTDSLYMKSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKK-----YAYEVNG 625 IYCDTDS+++ P + + DP LG W E+ + L K Y EV+G Sbjct: 450 IYCDTDSIHLTGTEVPEIIKDIVDPKKLGYWAHES-TFKRAKYLRQKTYIQDIYVKEVDG 508 Query: 626 KIKIAS 631 K+K S Sbjct: 509 KLKECS 514 >gil1072656[pir|IS51275 DNA polymerase - phage CP-1 >gi|836593|emb|CAA87725.1| (Z47794) DNA polymerase (Bacteriophage CP-1 Length = 568 Score = 53.5 bits (126), Expect = 6e-06 Identities = 104/464 (22%), Positives = 169/464 (36%), Gaps = 66/464 (14%) Query: 230 LTPEQLTYIHNDVIIL--GMCHIHYSDIFPNFDYNKLTFSLNIMESYLNNEMTRFQLLNQ 287 + PE + YIH DV IL G+ ++Y + F Y + +L + +F+ Sbjct: 152 IKPEWIDYIHVDVAILARGIFAMYYEENFTK--YTSASEALTEFKRIFRKSKRKFRDFFP 209 Query: 288 YQDIKISYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYPYVMY 347 D K+ D+ + G + K+ + +++ DINS YP M Sbjct: 210 ILDEKVD------------DFCRKHIVGAGRLPTLKHRGRTLNQLIDIYDINSMYPATML 257 Query: 348 HEKIPTWLYFYEHYSEPTLIPTFLDDDNYFSLY-KIDKDVFNDDL-LIKIKSRVLRQMXX 405 +P + + Y P + +D+Y+ + K D D+ L I+IK ++ Sbjct: 258 QNALPIGIP--KRYKGK---PKEIKEDHYYIYHIKADFDLKRGYLPTIQIKKKLDALRIG 312 Query: 406 XXXXXXXXXXXXXXXLRMIQDITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIKTQG 465 L + + H + E F +F +Y Sbjct: 313 VRTSDYVTTSKNEVIDLYLTNFDLDLFLKHYDATIMYVETLE-FQTESDLFDDYI----- 366 WO 00/32825 PCT/IB99/02040 285 Query: 466 KLKNKINMTSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYGIPALR--SHFNLFRLDDN 523 + Y Y E+ S E +K++LN LYG + S L LDD Sbjct: 367 --------- -TTYRYK ---- KENAQSPAEKQKAKIMLNSLYGKFGAKIISVKKLAYLDDK 412 Query: 524 NELYNIINGYKNTERNIL------FSTFVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDS 577 L +KN + + + FVTS + + ++ Q E DNF+Y DTDS Sbjct: 413 GILR-----FKNDDEEEVQPVYAPVALFVTSIARHFIISNAQ-----ENYDNFLYADTDS 462 Query: 578 LYMKSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKKYAYEVNGKIKIASAGIPKN 637 L++ +L+ DP GKW E + K L K Y E+ + + K Sbjct: 463 LHLFHSDSLVLD--- IDPSEFGKWAHEGRAV-KAKYLRSKLYIEELIQEDGTTHLDV-KG 517 Query: 638 AFDTSVDFETFVREQFFDGAIIENNKSIYNEQGTISIYPSKTEI 681 A T E E F GA E ++ +G IY + +I Sbjct: 518 AGMTPEIKEKITFENFVIGATFEGKRASKQIKGGTLIYETTFKI 561 >giI1429230lembiCAA67649| (X99260) DNA polymerase [Bacteriophage B1031 Length = 572 Score = 49.2 bits (115), Expect = le-04 Identities = 93/422 (22%), Positives = 155/422 (36%), Gaps = 88/422 (20%) Query: 229 KLTPEQLTYIHNDVIILGMCHIHYSDIFPNFDYNKLTFSLNIMESYLNNEMTR-----FQ 283 ++TPE+ YI ND+ I+ DI +++T + ++ + + T+ F Sbjct: 154 EITPEEYEYIKNDIEIIARA----LDIQFKQGLDRMTAGSDSLKGFKDILSTKKFNKVFP 209 Query: 284 LLNQYQDIKISYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYP 343 L+ D +I + YRGG N KY K I E D+NS YP Sbjct: 210 KLSLPMDKEI-----------------RRAYRGGFTWLNDKYKEKEIGEGMV-FDVNSLYP 252 Query: 344 YVMYHEKIPTWLYFYEHYSEPTLIPTFLDDDNYFSLYKIDKDVFNDDLLIKIKSRVLRQM 403 MY +P Y P + + D + LY I + F +L K + + Sbjct: 253 SQMYSRPLP--------YGAPIVFQGKYEKDEQYPLY-IQRIRFEFEL----KEGYIPTI 299 Query: 404 XXXXXXXXXXXXXXXXXXLRMIQ-DITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIK 462 ++ +T +D I+ + + +Y EY F + Sbjct: 300 QIKKNPFFKGNEYLKNSGAEPVELYLTNVDLELIQEH-YEMYNVEYIDGFK------FRE 352 Query: 463 TQGKLKNKINMTSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYG-----------IPAL 511 G K I+ + H + L+K++ + LYG +P L Sbjct: 353 KTGLFKEFIDKWTYVKTH---------EKGAKKQLAKLMFDSLYGKFASNPDVTGKVPYL 403 Query: 512 RSHFNL-FRLDDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNF 570 + +L FR+ D YK+ + F+T+ + + + Q D Sbjct: 404 KEDGSLGFRVGDEE--------YKDPVYTPM-GVFITAWARFTTITAAQACY-----DRI 449 Query: 571 IYCDTDSLYMKSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKK-----YAYEVNG 625 IYCDTDS+++ P + + DP LG W E+ + L K YA EV+G Sbjct: 450 IYCDTDSIHLTGTEVPEIIKDIVDPKKLGYWAHES-TFKRAKYLRQKTYIQDIYAKEVDG 508 Query: 626 KI 627 K+ Sbjct: 509 KL 510 >gil15724791emb|CAA65712| (X96987) DNA polymerase [Bacteriophage GA-1] Length = 578 Score = 46.1 bits (107), Expect = 0.001 Identities = 80/376 (21%), Positives = 146/376 (38%), Gaps = 54/376 (14%) Query: 234 QLTYIHNDVIILGMCHIHYSDIFPNFDYNKLTFSLNIMESYLNNEMTRFQLLNQYQDIKI 293 ++ Y+ +D++I+ + +F N D+ +T + + +Y EM + +Y + Sbjct: 162 EIEYLKHDLLIVALA---LRSMFDN-DFTSMTVGSDALNTY--KEMLGVKQWEKYFPVL- 214 Query: 294 SYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYPYVMYHEKIPT 353 + I+ Y+GG N KY + + D+NS YP +M ++ +P Sbjct: 215 --------SLKVNSEIRKAYKGGFTWVNPKYQGETVYGGMV-FDVNSMYPAMMKNKLLP- 264 Query: 354 WLYFYEHYSEPTLIPTFLDDDNYFSLYKIDKDVFNDDLLIKIKSRVLRQMXXXXXXXXXX 413 Y EP + + + LY F + KI ++ WO 00/32825 PCT/IB99/02040 286 Sbjct: 265 ------- YGEPVMFKGEYKKNVEYPLYIQQVRCFFELKKDKIPCIQIKGNARFGQNEYLS 317 Query: 414 XXXXXXXXLRMIQDITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIKTQGKLKNKINM 473 L +T +D I+ + + I+E E+ +F+ + I Sbjct: 318 TSGDEYVDLY----VTNVDWELIKKH-YDIFEEEFIGG--FMFKGF------------IGF 359 Query: 474 TSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYGIPALRSHFN--LFRLDDNNELYNIIN 531 Y + N S E+ + +K++LN LYG A + LD+N L Sbjct: 360 FDEYIDRFMEIKNSPDSSAEQSLQAKLMLNSLYGKFATNPDITGKVPYLDENGVLKFRKG 419 Query: 532 GYKNTERNILFST--- FVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDSLYMKSVVKPLL 588 K ER+ +++ F+T+ + N+L Q L FIY DTDS++++ + + Sbjct: 420 ELK--ERDPVYTPMGCFITAYARENILSNAQKLYP-----RFIYADTDSIHVEGLGEVDA 472 Query: 589 NPSLFDPIALGKWDIE 604 + DP LG WD E Sbjct: 473 IKDVIDPKKLGYWDHE 488 >gi1188511spP06950|DPOLBPPZA DNA POLYMERASE (EARLY PROTEIN GP2) >gi|75812|piriERBP2Z DNA-directed DNA polymerase (EC 2.7.7.7) - phage PZA >gil216051 (M11813) gene 2 product [Bacteriophage PZA] >gi12247411prf|11112171E ORF 2 [Bacteriophage PZA] Length = 572 Score = 45.3 bits (105), Expect = 0.002 Identities = 98/461 (21%), Positives = 166/461 (35%), Gaps = 110/461 (23%) Query: 198 QLKTDFNYTIFDKDNDMNDSEAYDYAVKCFAKLTPEQLTYIHNDVIILGMCHIHYSDIFP 257 ++ DF T+ D D + Y ++TP++ YI ND+ I+ + I Sbjct: 129 KIAKDFKLTVLKGDIDYHKERPVGY------EITPDEYAYIKNDIQIIAEALL----IQF 178 Query: 258 NFDYNKLTFSLNIMESYLNNEMTR-----FQLLNQYQDIKISYTHYHFHDMNFYDYIKSF 312 +++T + +++ + T+ F L+ D ++ Y Sbjct: 179 KQGLDRMTAGSDDLKGFKDIITTKKFKKVFPTLSLGLDKEVRYA------------------ 222 Query: 313 YRGGLNMYNTKYINKLIDEPCFSIDINSSYPYVMYHEKIPTWLYFYEHYSEPTLIPT--F 370 YRGG N ++ K I E D+NS YP MY +P Y EP + Sbjct: 223 YRGGFTWLNDRFKEKEIGEGMV-FDVNSLYPAQMYSRLLP -------- -YGEPIVFEGKYV 273 Query: 371 LDDDNYFSLYKID-----KDVFNDDLLIKIKSRVLRQMXXXXXXXXXXXXXXXXXXLRMI 425 D+D + I K+ + + IK +SR + Sbjct: 274 WDEDYPLHIQHIRCEFELKEGYIPTIQIK-RSRFYKGNEYLKSSGGEIADLW-------- 324 Query: 426 QDITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIKTQGKLKNKINMTSPYDYHITDDI 485 ++ +D + + + +Y EY F T G K+ I+ + I Sbjct: 325 -- VSNVD-LELMKEHYDLYNVEYISGLK------FKATTGLFKDFIDKWTHIKTTSEGAI 375 Query: 486 NEHPYSNEEVMLSKVVLNGLYG-----------IPALRSHFNL-FRLDDNNELYNIINGY 533 + L+K++LN LYG +P L+ + L FRL G Sbjct: 376 KQ---------LAKLMLNSLYGKFASNPDVTGKVPYLKENGALGFRL-----------GE 415 Query: 534 KNTERNIL--FSTFVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDSLYMKSVVKPLLNPS 591 + T+ + F+T+ + Y + Q D IYCDTDS+++ P + Sbjct: 416 EETKDPVYTPMGVFITAWARYTTITAAQACF-----DRIIYCDTDSIHLTGTEIPDVIKD 470 Query: 592 LFDPIALGKWDIENEQIDKMFVLNHKKYAY-----EVNGKI 627 + DP LG W E+ + L K Y EV+GK+ Sbjct: 471 IVDPKKLGYWAHES-TFKRAKYLRQKTYIQDIYMKEVDGKL 510 >gil2435429 (AF012250) unassigned reading frame (possible DNA polymerase) [Physarum polycephalum] Length = 544 Score = 44.9 bits (104), Expect = 0.002 Identities = 118/545 (21%), Positives = 206/545 (37%), Gaps = 104/545 (19%) Query: 179 TSIATLGKKLLDGGYLTESQLKTDFNYTIFDKDNDMNDSEAYDYAVKCFAKLTPEQLTYI 238 - T + L K L D + T Q F N M Y + CF L P++ I Sbjct: 62 TQLFNLLKSLQDSSFYTFKQ---------FTYQNIM-----YSLEISCF--LYPKKKILI 105 Query: 239 HNDVIILGMCHIHYSDIFPNFD-----YNKL--TFSLNIMESY-LNNEMTRFQLLNQYQD 290 D+ +I Y+D+ ++ YN++ +++NI Y L+ ++ + Sbjct: 106 -KDLYNFFSENIIYNDVVKDYKLLAILYNEIQTAYNININRKYILSTASLSLRIFKKSFP 164 WO 00/32825 PCT/IB99/02040 287 Query: 291 IKISYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYPYVMYHEK 350 K + D + +YI+ Y GG N I + + + + D+NS YPY+M EK Sbjct: 165 EKYRLIPHLTRDED--NYIRKSYIGGRNE-----IFEHVAQRNYFYDVNSLYPYIMKKEK 217 Query: 351 IPTWLYFYEHYSEPTLIPTFLDD-DNYFS ----LYKIDKDVFNDDLL---IKIKSRVLRQ 402 +P + Y + + F + +N+F L I+K N +L + IK+ V Sbjct: 218 MPIGI-- PEYRDKEYMKKFEKNIENFFGFIDVLITIEKTNNNIPVLPYRMGIKNNV-EV 273 Query: 403 MXXXXXXXXXXXXXXXXXXLRMIQDITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIK 462 L + Q I+ IY + ++++F+ Y + Sbjct: 274 GIIYAKGTLRGIYFSEEIKLALKQGYKIIE----------IYSAYEYKEKEVVFEEYVEQ 323 Query: 463 TQGK-LKNKINMTSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYG--------IPALRS 513 + LK K D + D L K +LN LYG I + Sbjct: 324 MYNRRLKAK-------DPALKD--------------LYKKLLNTLYGRFGLVYEQIDIISP 363 Query: 514 HFNLFRLDDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNFIYC 573 L + DN + + + + N ++ + ++ + F Y T + + IY Sbjct: 364 EKEL--ITDNTYISHDTTEFIDITANTCYNNIAITSAITSYARIFMYNTILNYNLHVIYI 421 Query: 574 DTDSLYMKSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKKYAY-EVNGKIKIASA 632 DTD L++K+ P+ + +L +GK+ +E+ + F+ N K Y Y +N I Sbjct: 422 DTDGLFLKN--- PIPDIALTTSKEMGKFRLESINAEAHFIAN-KFYIYAPINSPIIYKFK 477 Query: 633 GIPK-----NAFDTSVDFETFVR----EQFFDGAIIENNKSIYNEQGT-----ISIYPSK 678 GIP N D + + +F +1 NN Y+ Q + I Y + Sbjct: 478 GIPLQKPIFNIHDIITQHKKILNITLGHHYFTFSIRLNNNQTYSFQASRKRKLIPNYKTT 537 Query: 679 TEIVC 683 I+C Sbjct: 538 PWIIC 542 >gijl084487|pir||S41618 DNA polymerase - slime mold (Physarum polycephalum) >gij509721|dbjlBAA06121.1I (D29637) DNA polymerase {Physarum polycephalum] Length = 547 Score = 44.9 bits (104), Expect = 0.002 Identities = 118/545 (21%), Positives = 206/545 (37%), Gaps = 104/545 (19%) Query: 179 TSIATLGKKLLDGGYLTESQLKTDFNYTIFDKDNDMNDSEAYDYAVKCFAKLTPEQLTYI 238 T + L K L D + T Q F N M Y + CF L P++ I Sbjct: 65 TQLFNLLKSLQDSSFYTFKQ---------FTYQNIM-----YSLEISCF--LYPKKKILI 108 Query: 239 HNDVIILGMCHIHYSDIFPNFD-----YNKL--TFSLNIMESY-LNNEMTRFQLLNQYQD 290 D+ +I Y+D+ ++ YN++ +++NI Y L+ ++ + Sbjct: 109 -KDLYNFFSENIIYNDVVKDYKLLAILYNEIQTAYNININRKYILSTASLSLRIFKKSFP 167 Query: 291 IKISYTHYHFHDMNFYDYIKSFYRGGLNMYNTKYINKLIDEPCFSIDINSSYPYVMYHEK 350 K + D + +YI+ Y GG N I + + + + D+NS YPY+M EK Sbjct: 168 EKYRLIPHLTRDED--NYIRKSYIGGRNE-----IFEHVAQRNYFYDVNSLYPYIMKKEK 220 Query: 351 IPTWLYFYEHYSEPTLIPTFLDD-DNYFS----LYKIDKDVFNDDLL---IKIKSRVLRQ 402 +P + Y + + F + +N+F L I+K N +L + IK+ V Sbjct: 221 MPIGI---PEYRDKEYMKKFEKNIENFFGFIDVLITIEKTNNNIPVLPYRMGIKNNV-EV 276 Query: 403 MXXXXXXXXXXXXXXXXXXLRMIQDITGIDCMHIRVNSFVIYECEYFHARDIIFQNYFIK 462 L + Q I+ IY + ++++F+ Y + Sbjct: 277 GIIYAKGTLRGIYFSEEIKLALKQGYKIIE----------IYSAYEYKEKEVVFEEYVEQ 326 Query: 463 TQGK-LKNKINMTSPYDYHITDDINEHPYSNEEVMLSKVVLNGLYG--------IPALRS 513 + LK K D + D L K +LN LYG I + Sbjct: 327 MYNRRLKAK-------DPALKD--------------LYKKLLNTLYGRFGLVYEQIDIISP 366 Query: 514 HFNLFRLDDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNFIYC 573 L + DN + + + + N ++ + ++ + F Y T + + IY Sbjct: 367 EKEL--ITDNTYISHDTTEFIDITANTCYNNIAITSAITSYARIFMYNTILNYNLHVIYI 424 Query: 574 DTDSLYMKSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKKYAY-EVNGKIKIASA 632 DTD L++K+ P+ + +L +GK+ +E+ + F+ N K Y Y +N I Sbjct: 425 DTDGLFLKN--- PIPDIALTTSKEMGKFRLESINAEAHFIAN-KFYIYAPINSPIIYKFK 480 Query: 633 GIPK-----NAFDTSVDFETFVR----EQFFDGAIIENNKSIYNEQGT-----ISIYPSK 678 WO 00/32825 PCT/IB99/02040 288 GIP N D + + +F +I NN Y+ Q + I Y + Sbjct: 481 GIPLQKPIFNIHDIITQHKKILNITLGHHYFTFSIRLNNNQTYSFQASRKRKLIPNYKTT 540 Query: 679 TEIVC 683 I+C Sbjct: 541 PWIIC 545 >gil4877819igbjAAD31446.1| (AF133505) DNA polymerase [Neurospora crassa] Length = 1035 Score = 44.1 bits (102), Expect = 0.004 Identities = 36/172 (20%), Positives = 82/172 (46%), Gaps = 14/172 (8%) Query: 521 DDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDSLYM 580 + N EL + ++G K+ I ++ + + ++ ++ ++++ S Y DTDS+++ Sbjct: 817 EKNYELLSYLDGEKDDGFIINSTSIAAATASWSRILMYKHIINSA------YTDTDSIFV 870 Query: 581 KSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKKYAYEVNGKIKIASAGIPKNAFD 640 + KPL + + + K + + I + ++ K Y + GK++I GI KN + Sbjct: 871 E---KPLDSAFIGEGCGKFKAEYNGQLIKRAIFISGKLYLLDFGGKLEIKCKGITKNKDN 927 Query: 641 TSVDFETFVREQFFDG --- AIIENNKSIYNEQGTISIYPSKTEIVCGNVYDE 689 T++ + E ++G + + E GT.++ K ++ G YD+ Sbjct: 928 TTHNLDINDFEALYNGESRVLFQERWGRSLELGTVTVKYQKYNLISG--YDK 977 >gil461962spIP33537IDPOMNEUCR PROBABLE DNA POLYMERASE >gij283351|pir|I|S26985 probable DNA-directed DNA polymerase (EC 2.7.7.7) - Neurospora crassa mitochondrion plasmid maranhar (SGC3) >gil578156jembICAA39046| (X55361) putative DNA polymerase (Neurospora crassa] Length = 1021 Score = 44.1 bits (102), Expect = 0.004 Identities = 36/172 (20%), Positives = 82/172 (46%), Gaps = 14/172 (8%) Query: 521 DDNNELYNIINGYKNTERNILFSTFVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDSLYM 580 + N EL + ++G K+ I ++ + + ++ ++ ++++ S Y DTDS++ Sbjct: 815 EKNYELLSYLDGEKDDGFIINSTSIAAATASWSRILMYKHIINSA------YTDTDSIFV 868 Query: 581 KSVVKPLLNPSLFDPIALGKWDIENEQIDKMFVLNHKKYAYEVNGKIKIASAGIPKNAFD 640 + KPL + + + K + + I + ++ K Y + GK++I GI KN + Sbjct: 869 E---KPLDSAFIGEGCGKFKAEYNGQLIKRAIFISGKLYLLDFGGKLEIKCKGITKNKDN 925 Query: 641 TSVDFETFVREQFFDG---AIIENNKSIYNEQGTISIYPSKTEIVCGNVYDE 689 T++ + E ++G + + E GT++ K ++ G YD+ Sbjct: 926 TTHNLDINDFEALYNGESRVLFQERWGRSLELGTVTVKYQKYNLISG--YDK 975 >gil2499511|splQ1247116P22 YEAST 6-PHOSPHOFRUCTO-2-KINASE 2 (PHOSPHOFRUCTOKINASE 2 II) (6PF-2-K 2) >gil2131162|pir||S61066 6-phosphofructo-2-kinase (EC 2.7.1.105) - yeast (Saccharomyces cerevisiae) >gil2131163|pir|S71026 6-phosphofructo-2-kinase (EC 2.7.1.105) - yeast (Saccharomyces cerevisiae) >gil1085116|emb|CAA62371| (X90861) 6-phosphofructo-2-kinase Saccharomyces cerevisiae] >gi|l420028IembiCAA99157 (Z74878) ORF YOL136c [Saccharomyces cerevisiae} >gi11628439|embICAA64733| (X95465) 6-phosphofructo-2-kinase [Saccharomyces cerevisiae] Length = 397 Score = 40.6 bits (93), Expect = 0.041 Identities = 48/208 (23%), Positives = 92/208 (44%), Gaps = 29/208 (13%) Query: 175 MKTNTSIATLGKKLLDGGYLTESQLKTDFNYTIFDKDNDMNDSEAYDYAVKCFAKLTPEQ 234 ++ S AT+ K LL L+ + + FN K+ND ++ +A++T ++ Sbjct: 139 IRRQISCATISKPLL----LSNTSSEDLFN----PKNNDKKET---------YARITLQK 181 Query: 235 LTY-IHNDVIILGMCHIHYSDIFPNFDYNKLTFSLNIMESYLNNEMTRFQLLN---QYQD 290 L + I+ND +G+ S I + F + S+ +E++ F L+ Q Sbjct: 182 LFHEINNDECDVGIFDATNSTI------ERRRFIFEEVCSFNTDELSSFNLVPIILQVSC 235 WO 00/32825 PCT/IB99/02040 289 Query: 291 IKISYTHYHFHDMNFY-DYIKSFYRGGLNMYNTKYINKLIDEPCFSID-INSSYPYVMYH 348 S+ Y+ H+ +F DY+ Y + + + + FS+D N + Y+ H Sbjct: 236 FNRSFIKYNIHNKSFNEDYLDKPYELAIKDFAKRLKHYYSQFTPFSLDEFNQIHRYISQH 295 Query: 349 EKIPTWLYFYEHYSEPTLIPTFLDDDNY 376 E+I T L+F+ + + P L+ +Y Sbjct: 296 EEIDTSLFFFNVINAGVVEPHSLNQSHY 323 >gil2258375gblAAD11909.1| (AF007261) transcription initiation factor sigma (Reclinomonas americana] Length = 532 Score = 39.9 bits (91), Expect = 0.070 Identities = 49/205 (23%), Positives = 84/205 (40%), Gaps = 14/205 (6%) Query: 100 NHFLLKDTMRYFDNITRENIYLKSAEENEHTLKMKEATILAKNQNVIL--- EKRVKSSIN 156 N+ + + F + ++IY+ + +KE L K NVI+ K +K N Sbjct: 177 NYLVKNSYLNLFKTVPHDSIYMNYSYIQTPLNILKEYLQLIKIINVIILQINKNIKKKNN 236 Query: 157 LDLTMFLNGFKFNIIDNFM---KTNTSIATLGKKLLDGGYLTESQLKTDFNYTIFDKDND 213 L..++FL F + N++ K + + + K L Y+T L T Y K Sbjct: 237 LNISLFLYKFYQELKWNYIFINKISRNTQKINIKTLKNSYITFYNLITFIQYYTTKKQRL 296 Query: 214 MNDSEAYDYAVKCFAK--LTPEQLTYIHNDVIILGMCHIHYSDIFPNFDYN-KLTFSLNI 270 D +K F K P+ +N +I G+ HI+ + N K+T I Sbjct: 297 KKDIFYKQIFIKTFLKQHKIPKINKIKNNSLIKYGLTHIYDMILISILRENIKVTLKNRI 356 Query: 271 MESYLNNEMTRFQLLNQYQDIKISY 295 + +Y+ T + QY +KI Y Sbjct: 357 IFNYMPYITT---ISKQY--VKIGY 376 >gij15734|emb|CAA37450| (X53370) DNA polymerase (AA 1-575) [Bacteriophage phi-29] Length = 575 Score = 39.5 bits (90), Expect = 0.092 Identities = 41/150 (27%), Positives = 64/150 (42%), Gaps = 36/150 (24%) Query: 497 LSKVVLNGLYG-----------IPALRSHFNL-FRLDDNNELYNIINGYKNTERNIL--F 542 L+K++LN LYG +P L+ + L FRL G + T+ + Sbjct: 381 LAKLMLNSLYGKFASNPDVTGKVPYLKENGALGFRL-----------GEEETKDPVYTPM 429 Query: 543 STFVTSRSLYNLLVPFQYLTESEIDDNFIYCDTDSLYMKSVVKPLLNPSLFDPIALGKWD 602 F+T+ + Y + Q D IYCDTDS+++ P + + DP LG W Sbjct: 430 GVFITAWARYTTITAAQACY-----DRIIYCDTDSIHLTGTEIPDVIKDIVDPKKLGYWA 484 Query: 603 IENEQIDKMFVLNHKKYAY-----EVNGKI 627 E+ ++ L K Y EV+GK+ Sbjct: 485 HES-TFKRVKYLRQKTYIQDIYMKEVDGKL 513 Query= pt|110872 44AHJDORFOO2 Phage 44AHJD ORF 13789-573213 1 (647 letters) >gij135273|sp|P276221TAGC_BACSU TEICHOIC ACID BIOSYNTHESIS PROTEIN C >gil478126|pir||D49757 techoic acid biosynthesis protein tagC - Bacillus subtilis (strain 168) >gil143727 (M57497) putative (Bacillus subtilis] >gil2636103|embjCAB15594.1| (Z99122) alternate gene name: dinC (Bacillus subtilis] Length = 442 Score = 112 bits (278), Expect = 7e-24 Identities = 91/314 (28%), Positives = 147/314 (45%), Gaps = 58/314 (18%) Query: 152 FELNELEPKFVMGFGGIRNAVNQSINIDKETNHMYSTQSDS ---- QKPEGFWINKLTPSG 207 F+ + PK V QS N D++ + +Y+TQ S + + I +L+ G Sbjct: 7 FDFTNITPKLFTELRVADKTVLQSFNFDEKNHQIYTTQVASGLGKDNTQSYRITRLSLEG 66 Query: 208 DLISSMRIVQGGHGTTIGLERQSNGEMKIWLHHD-----GVAKLLQVAYKDNYVLDLEEA 262 + SM + GGHGT IG+E + NG + IW +D ++L+ YK LD E + Sbjct: 67 LQLDSMLLKHGGHGTNIGIENR-NGTIYIWSLYDKPNETDKSELVCFPYKAGATLD-ENS 124 WO 00/32825 PCT/IB99/02040 290 Query: 263 KGLTDYTPQSLLNKHTFTPLIDEANDKLILRFGDGTIQVRSRADVKNHIDNVEKEMTIDN 322 K L ++ H TP +D N +L +R + D KN+ N ++ +TI N Sbjct: 125 KELQRFSNMPF--DHRVTPALDMKNRQLAIR----------QYDTKNN--NNKQWVTIFN 170 Query: 323 SE----NNDN-----------RWMQGIAVDGDDLYWLSGNSSVNSHVQIGKYSLTTGQKI 367 + N +N ++QG +D LYW +G+++ S+ + + Sbjct: 171 LDDAIANKNNPLYTINIPDELHYLQGFFLDDGYLYWYTGDTNSKSYPNL--------ITV 222 Query: 368 YDYPFKLSYQDGINFPRD-------NFKEPEGICIYTNPKTKRKSLLLAMTNGGGGKRFH 420 +D K+ Q I +D NF+EPEGIC+YTNP+T KSL++ +T+G G R Sbjct: 223 FDSDNKIVLQKEITVGKDLSTRYENNFREPEGICMYTNPETGAKSLMVGITSGKEGNRIS 282 Query: 421 NLYGFFQLGEYEHF 434 +Y + YE+F Sbjct: 283 RIYAYH---SYENF 293
>
g i1142847 (M64050) DNase inhibitor [Bacillus subtilis] Length = 125 Score = 51.9 bits (122), Expect = le-05 Identities = 35/116 (30%), Positives = 55/116 (47%), Gaps = 10/116 (8%) Query: 152 FELNELEPKFVMGFGGIRNAVNQSINIDKETNHMYSTQSDS ---- QKPEGFWINKLTPSG 207 F+ + PK V QS N D++ + +Y+TQ S + + I +L+ G Sbjct: 7 FDFTNITPKLFTELRVADKTVLQSFNFDEKNHQIYTTQVASGLGKDNTQSYRITRLSLEG 66 Query: 208 DLISSMRIVQGGHGTTIGLERQSNGEMKIWLHHD-----GVAKLLQVAYKDNYVLD 258 + SM + GGHGT IG+E + NG + IW +D ++L+ YK LD Sbjct: 67 LQLDSMLLKHGGHGTNIGMENR-NGTIYIWSLYDKPNETDKSELVCFPYKAGATLD 121 >gij4038407 (AF103943) factor C protein precursor [Streptomyces griseus] Length = 324 Score = 39.1 bits (89), Expect = 0.10 Identities = 61/269 (22%), Positives = 102/269 (37%), Gaps = 33/269 (12%) Query: 172 VNQSINIDKETNHMYSTQSDSQKPEG--- FWINKLTPSGDLISSMRIVQGGHGTTIGLER 228 V QS D ++ Q S P+ I +L SG+ + M ++ GHG +IG + Sbjct: 66 VQQSFTFDIVNRRLFVAQLKSGSPDDSGDLCITQLDFSGNKLGHMYLLGFGHGVSIGAQ- 124 Query: 229 QSNGEMKIWLHHDGVAKLLQVAYKDNYVLDLEEAKGLTDYTPQSLLNKHTFTP------- 281 + +W D + + + + T S L KH P Sbjct: 125 PVGADTYLWTEVD-----VNSNARGTRLARFKWNNGATLSRTSSALAKHQPVPGATEMTC 179 Query: 282 LIDEANDKLILRFGDGTIQVRSRADVKNHIDNVEKEMTIDNSENNDNRWMQGIAVDGDDL 341 ID N+++ +R+ + + +V + V + D QG A+ G + Sbj ct: 180 AIDPVNNRMAIRYLTASGRRYGIYNVADIAAGVYDKPLSDVPHPTGLGTFQGYALYGSYV 239 Query: 342 YWLSGN-------SSVNSHVQIGKYSLTTGQKIYDYPFKLSYQDGINFPRDNFKEPEGIC 394 Y L+GN + NS+V + TG + + + G F+EPEG+ Sbjct: 240 YQLTGNPYGPDNPNPGNSYVS--SVDVNTGALVQ----RAFTRAGSTL---TFREPEGMG 290 Query: 395 IYTNPKTKRKSLLLAMTNGGGGKRFHNLY 423 IY + + L L +G G R NL+ Sbjct: 291 IYRTAAGEVR-LFLGFASGVAGDRRSNLF 318 Query= ptj110873 44AHJDORFOO3 Phage 44AHJD ORF 16626-838912 1 (587 letters) >gil138123jsp|P04331|VG9_BPPH2 TAIL PROTEIN (LATE PROTEIN GP9) >gi|75850|pir|IWMBPT9 gene 9 protein - phage phi-29 >gil215327 (M14782) tail protein [Bacteriophage phi-29] >gij225364jprf||1301270D gene 9 [Bacillus sp.] Length = 599 Score = 92.4 bits (226), Expect = 8e-18 Identities = 126/618 (20%), Positives = 251/618 (40%), Gaps = 71/618 (11%) Query: 5 TNFKFFYNTPFT-DYQNTIHFNSNKERDDYFLNGRHFKSLDYSKQPY-NFIRDRMEINVD 62 TN + + PF+ DY+NT F S+ + ++F R + + SK + F ++ ++V Sbjct: 9 TNVRILADVPFSNDYKNTRWFTSSSNQYNWF--NRKSRVYEMSKVTFMGFRENKPYVSVS 66 WO 00/32825 PCT/IB99/02040 291 Query: 63 MQWHDAQGINYMTFLS-DFEDRRYYAFVNQIEYVNDVVVKIYFVIDTIMTYTQGNVLEQL 121 + +Y+ F + D+ ++ +YAFV ++E+ N V ++F ID + T+ ++ Sbjct: 67 LPIDKLYSASYIMFQNADYGNKWFYAFVTELEFKNSAVTYVHFEIDVLQTWMFDMKFQES 126 Query: 122 SNVNIERQHLSKRTYNYMLPMLRNNDDVLKVSNKNYVYNQMQQYLENLVLFQSSADLSKK 181 I R+H+ K + P + D+ L ++ + + + ++F S Sbjct: 127 F---IVREHV-KLWNDDGTPTINTIDEGLSYGSEYDIVSVENHKPYDDMMFLVIISKSIM 182 Query: 182 FGT--KKEPNLDTSKGTIYDNITSPVNLYVMEYGDFINFMDKMSAYPWITQNFQK--- -V 235 GT ++E L+ ++ + + P+ Y+ + + D +I N V Sbjct: 183 HGTPGEEESRLNDINASL-NGMPQPLCYYIHPF-----YKDGKVPKTYIGDNNANLSPIV 236 Query: 236 QMLPKDFINTKDLEDVKTSEKITGLKTLKQGGKSKEWSLK-DLSL---------SFSNLQ 285 ML F + D+ + +T LK K+ + LK D + N+ Sbjct: 237 NMLTNIFSQKSAVNDI-VNMYVTDYIGLKLDYKNGDKELKLDKDMFEQAGIADDKHGNVD 295 Query: 286 EMMLSK ------------------- -KDEFKHMIRNEYMTIEFYDWNGNTMLLDAGKISQK 326 + + K KD+ ++ Y E D+ GN M L I+ Sbjct: 296 TIFVKKIPDYEALEIDTGDKWGGFTKDQESKLMMYPYCVTEITDFKGNHMNLKTEYINNS 355 Query: 327 TGVKLRTKSIIGYHNEVRVYPVDYNSAENDRPILAKNKEILIDTGSFLNTNITFNSFAQV 386 +K++ + +G N+V DYN+ D + N+ S +N N Sbjct: 356 K-LKIQVRGSLGVSNKVAYSVQDYNA---DSALSGGNRLTASLDSSLINNNPN------- 404 Query: 387 PILINNGILGQSQQANRQ--KNAESQLITNRIDNVLNG---SDPKSRFYDAVSVASNLSP 441 I I N L Q N+ +N +S ++ N I ++ G + + A+ +AS++ Sbjct: 405 DIAILNDYLSAYLQGNKNSLENQKSSILFNGIMGMIGGGISAGASAAGGSALGMASSV-- 462 Query: 442 TALFGKFNEEYNFYKQQQAEYKDLALQPPSVTESEMGNAFQIANSINGLTMKISVPSPKE 501 T + + QA+ D+A PP +T+ AF N G+ + + Sbjct: 463 TGMTSTAGNAVLQMQAMQAKQADIANIPPQLTKMGGNTAFDYGNGYRGVYVIKKQLKAEY 522 Query: 502 ITFLQKYYMLFGFEVNDYNSFIEPINSMTVCNYLKCTGTYTIRDIDPMLMEQLKAILESG 561 L ++ +G+++N + + NY++ + DI+ +++++ I ++G Sbjct: 523 RRSLSSFFHKYGYKINRVKK--PNLRTRKAFNYVQTKDCFISGDINNNDLQEIRTIFDNG 580 Query: 562 VRFWHNDGSGNPMLQNPL 579 + WH D GN ++N L Sbjct: 581 ITLWHTDNIGNYSVENEL 598 >gi|1381241spIP07534|VG9_BPPZA TAIL PROTEIN (LATE PROTEIN GP9) >giI75849Ipir||WMBP9Z gene 9 protein - phage PZA >giJ216058 (M11813) tail protein [Bacteriophage PZA] Length = 599 Score = 81.9 bits (199), Expect = le-14 Identities = 127/618 (20%), Positives = 248/618 (39%), Gaps = 71/618 (11%) Query: 5 TNFKFFYNTPFT-DYQNTIHFNSNKERDDYFLNGRHFKSLDYSKQPYNFIRDRME-INVD 62 TN + + PF+ DY+NT F S+ + ++F + + SK + R+ I+V Sbjct: 9 TNVRILADVPFSNDYKNTRWFTSSSNQYNWF--NSKTRVYEMSKVTFQGFRENKSYISVS 66 Query: 63 MQWHDAQGINYMTFLS-DFEDRRYYAFVNQIEYVNDVVVKIYFVIDTIMTYTQGNVLEQL 121 ++ +Y+ F + D+ ++ +YAFV ++EY N ++F ID + T+ N+ Q Sbjct: 67 LRLDLLYNASYIMFQNADYGNKWFYAFVTELEYKNVGTTYVHFEIDVLQTW-MFNIKFQE 125 Query: 122 SNVNIERQHLSKRTYNYMLPMLRNNDDVLKVSNKNYVYN--QMQQYLENLVLFQSSADLS 179 S I R+H+ K + P + D+ L ++ + + + Y + + L S + Sbjct: 126 SF--IVREHV-KLWNDDGTPTINTIDEGLNYGSEYDIVSVENHRPYDDMMFLVVISKSIM 182 Query: 180 KKFGTKKEPNLDTSKGTIYDNITSPVNLYVMEY-----------GD-------FINFMDK 221 + E L+ ++ + + P+ Y+ + GD +N + Sbjct: 183 HGTAGEAESRLNDINASL-NGMPQPLCYYIHPFYKDGKVPKTFIGDNNANLSPIVNMLTN 241 Query: 222 MSAYPWITQNFQKVQMLPKDFINTK--------DLEDVKTSEKITGLKTLKQGGKSKEWS 273 + + N V M D+I K +L+ K + G+ K G + Sbjct: 242 IFSQKSAVNNI--VNMYVTDYIGLKLDYKNGDKELKLDKDMFEQAGIADDKHGNVDTIFV 299 Query: 274 LKDL---SLSFSNLQEMMLSKKDEFKHMIRNEYMTIEFYDWNGNTMLLDAGKISQKTGVK 330 K +L + KD+ ++ Y E D+ GN M L I +K Sbjct: 300 KKIPDYETLEIDTGDKWGGFTKDQESKLMMYPYCVTEVTDFKGNHMNLKTEYIDNNK-LK 358 Query: 331 LRTKSIIGYHNEVRVYPVDYNSAENDRPILAKNKEILIDTGSFLNTNITFNSFAQVPILI 390 ++ + +G N+V DYN+ + L+ + L+T++ N+ + I+ WO 00/32825 PCT/IB99/02040 292 Sbjct: 359 IQVRGSLGVSNKVAYSIQDYNAGGS----LSGGDRLTAS----LDTSLINNNPNDIAII- 409 Query: 391 NNGILGQSQQANRQ--KNAESQLITNRIDNVLNGSDPKSRFYDAVSVASNLSP------- 441 N L Q N+ +N +S ++ N I +L G A + A SP Sbjct: 410 -NDYLSAYLQGNKNSLENQKSSILFNGIVGMLGGG------VSAGASAVGRSPFGLASSV 462 Query: 442 TALFGKFNEEYNFYKQQQAEYKDLALQPPSVTESEMGNAFQIANSINGLTMKISVPSPKE 501 T + + QA+ D+A PP +T+ AF N G+ + + Sbjct: 463 TGMTSTAGNAVLDMQALQAKQADIANIPPQLTKMGGNTAFDYGNGYRGVYVIKKQLKAEY 522 Query: 502 ITFLQKYYMLFGFEVNDYNSFIEPINSMTVCNYLKCTGTYTIRDIDPMLMEQLKAILESG 561 L ++ +G+++N + + NY++ + DI+ +++++ I ++G Sbjct: 523 RRSLSSFFHKYGYKINRVKK--PNLRTRKAYNYIQTKDCFISGDINNNDLQEIRTIFDNG 580 Query: 562 VRFWHNDGSGNPMLQNPL 579 + WH D GN ++N L Sbjct: 581 ITLWHTDDIGNYSVENEL 598 >gil1429238|embCAA67657| (X99260) tail protein [Bacteriophage B103] Length = 598 Score = 77.6 bits (188), Expect = 2e-13 Identities = 130/623 (20%), Positives = 240/623 (37%), Gaps = 86/623 (13%) Query: 5 TNFKFFYNTPFT-DYQNTIHFNSNKERDDYFLNGRHFKSLDYSKQPYNFI---RDRMEIN 60 T+ + F N PF+ DY++T F + + YF + K + NF+ I Sbjct: 9 TDVRIFSNVPFSNDYKSTRWFTNADAQYSYF ---- NAKPRVHVINECNFVGLKEGTPHIR 64 Query: 61 VDMQWHDAQGINYMTFLS-DFEDRRYYAFVNQIEYVNDVVVKIYFVIDTIMTYTQGNVLE 119 V+ + D YM F + + ++ +Y FV ++EYVN V +YF ID I T+ + Sbjct: 65 VNKRIDDLYNACYMIFRNTQYSNKWFYCFVTRLEYVNSGVTNLYFEIDVIQTW-MFDFKF 123 Query: 120 QLSNVNIERQHLSKRTYNYMLPMLRNNDDVLKVSNKNYVYNQMQQYLENLVLFQSSADLS 179 Q S + E Q + P+ D+ L + V Q ++F S Sbjct: 124 QPSYIVREHQEMWDANNE---PLTNTIDEGLNYGTEYDVVAVEQYKPYGDLMFMVCISKS 180 Query: 180 KKFGTKKEPNLDTSKGTIYDNITS --- PVNLYVMEYGDFINFMDKMSAYPWITQNFQKVQ 236 ' K T E G I NI P++ YV + + D S P +T +VQ Sbjct: 181 KMHATAGET---FKAGEIAANINGAPQPLSYYVHPF-----YEDGSS--PKVTIGSNEVQ 230 Query: 237 ML-PKDFINTKDLEDVKTSEKITGLKT------LKQGGKSKEWSLKDLSLSFSNL----- 284 + P DF+ ++ + ++ T + +K SL+D + + Sbjct: 231 VSKPTDFLKNMFTQEHAVNNIVSLYVTDYIGLNIHYDESAKTMSLRDTMFEHAQIADDKH 290 Query: 285 -------------- QEMMLSKKDEFKHMIRNEYMTIEFY--------DWNGNTMLLDAGK 322 +E + +F NE + Y D+ GN + + Sbjct: 291 PNVNTIYLKEVKEYEEKTIDTGYKFASFANNEQSKLLMYPYCVTTITDFKGNQIDIKNEY 350 Query: 323 ISQKTGVKLRTKSIIGYHNEVRVYPVDYNS --- AENDRPILAKNKEILIDTGSFLNTNIT 379 ++ + +K++ + +G N+V DYN+ D+ + A NT++ Sbjct: 351 VNG-SNLKIQVRGSLGVSNKVTYSVQDYNADTTLSGDQNLTAS-----------CNTSLI 398 Query: 380 FNSFAQVPILINNGILGQSQQANRQ--KNAESQLITNRIDNVLN---GSDPKSRFYDAVS 434 N+ V I+ N L Q N+ +N + ++ N + ++L G+ + AV Sbjct: 399 NNNPNDVAII--NDYLSAYLQGNKNSLENQKDSILFNGVMSMLGNGIGAVGSAATGSAVG 456 Query: 435 VASNLSPTALFGKFNEEYNFYKQQQAEYKDLALQPPSVTESEMGNAFQIANSINGLTMKI 494 VAS S T + + QA+ D+A PP + + A+ N G+ + Sbjct: 457 VAS--SATGMVSSAGNAVLQIQGMQAKQADIANTPPQLVKMGGNTAYDYGNGYRGVYVIK 514 Query: 495 SVPSPKEITFLQKYYMLFGFEVNDYNSFIEPINSMTVCNYLKCTGTYTIRDIDPMLMEQL 554 + L + +G++ N + + + NY++ I +++ ++++ Sbjct: 515 KQIKEEYRNILSDFSRKYGYKTNLVK--MPNLRTRESYNYVQTKDCNIIGNLNNEDLQKI 572 Query: 555 KAILESGVRFWHNDGSGNPMLQN 577 + I +SG+ WH D G+ L N Sbjct: 573 RTIFDSGITLWHADPVGDYTLNN 595 >gil215339 (M12456) p9 tail protein [Bacteriophage phi-29] >gil224163|prfj11011232C protein p9,tail [Bacteriophage phi-29] Length = 335 WO 00/32825 PCT/IB99/02040 293 Score = 71.0 bits (171), Expect = 2e-11 Identities = 64/293 (21%), Positives = 123/293 (41%), Gaps = 20/293 (6%) Query: 292 KDEFKHMIRNEYMTIEFYDWNGNTMLLDAGKISQKTGVKLRTKSIIGYHNEVRVYPVDYN 351 KD+ ++ Y E D+ GN M L I+ +K++ + +G N+V DYN Sbjct: 57 KDQESKLMMYPYCVTEITDFKGNHMNLKTEYINNSK-LKIQVRGSLGVSNKVAYSVQDYN 115 Query: 352 SAENDRPILAKNKEILIDTGSFLNTNITFNSFAQVPILINNGILGQSQQANRQ--KNAES 409 + D + N+ S +N N I I N L Q N+ +N +S Sbjct: 116 A---DSALSGGNRLTASLDSSLINNNPN-------DIAILNDYLSAYLQGNKNSLENQKS 165 Query: 410 QLITNRIDNVLNG--- SDPKSRFYDAVSVASNLSPTALFGKFNEEYNFYKQQQAEYKDLA 466 ++ N I ++ G + + A+ +AS++ T + + QA+ D+A Sbjct: 166 SILFNGIMGMIGGGISAGASAAGGSALGMASSV--TGMTSTAGNAVLQMQAMQAKQADIA 223 Query: 467 LQPPSVTESEMGNAFQIANSINGLTMKISVPSPKEITFLQKYYMLFGFEVNDYNSFIEPI 526 PP +T+ AF N G+ + + L ++ +G+++N + Sbjct: 224 NIPPQLTKMGGNTAFDYGNGYRGVYVIKKQLKAEYRRSLSSFFHKYGYKINRVKK--PNL 281 Query: 527 NSMTVCNYLKCTGTYTIRDIDPMLMEQLKAILESGVRFWHNDGSGNPMLQNPL 579 + NY++ + DI+ +++++ I ++G+ WH D GN ++N L Sbjct: 282 RTRKAFNYVQTKDCFISGDINNNDLQEIRTIFDNGITLWHTDNIGNYSVENEL 334 >gi111819681embCAA87738.1 (Z47794) tail protein [Bacteriophage CP-1) Length = 230 Score = 53.9 bits (127), Expect = 3e-06 Identities = 29/113 (25%), Positives = 54/113 (47%), Gaps = 3/113 (2%) Query: 1 MRKLTNFKFFYNTPF-TDYQNTIHFNSNKERDDYFLNGRHFKSLDYSKQPYNFIRDRMEI 59 M++ T + +PF DY N I+F + + +D+F + Y ++ + I Sbjct: 1 MQESTKIWLYAKSPFKNDYANVINFETRESMEDFFTKKNPHIEIVYEYDKFQYTQRNGSI 60 Query: 60 NVDMQWHDAQGINYMTFLSDFEDRRYYAFVNQIEYVNDVVVKIYFVIDTIMTY 112 V + + + YM F+++ R YYAFV + Y+N+ +I + +D TY Sbjct: 61 VVSGRVEKYENVTYMRFINN--GRTYYAFVFDVLYINEDATRIIYEVDVWNTY 111 >gil1181970|embICAA87740.1| (Z47794) tail protein (Bacteriophage CP-1] Length = 586 Score = 42.2 bits (97), Expect = 0.010 Identities = 79/381 (20%), Positives = 139/381 (35%), Gaps = 92/381 (24%) Query: 277 LSLSFSNLQEMMLSK--KDEFK---HMIRNEYMTIEFYDWNGNTMLLDAG----KISQKT 327 L +++ +QE + S KD+ + ++ +E+ IE YD GN+ + I + Sbjct: 187 LKIAYDQIQEGLRSYMGKDDLEIEVQLLNSEFTEIELYDIYGNSYVYQPQYLPRTIDEAH 246 Query: 328 GVKLRTKSIIGYHNEVRVYPVDYNSAEN----DRPIL------------------------- 360 K+ +G N+V + ++YN+A N D+ IL Sbjct: 247 KYKVIVSGSLGDSNQVHINFLEYNNANNVSYADKNILDSLESGDWAEHNPEHFKYGLNDV 306 Query: 361 -AKNKEILIDT-GSFLNTNITFNSFAQVPILINNGILGQSQQANRQKNAESQLITNRIDN 418 K+ IL D S++ ++ Q+ N +L QS + ++ A + + Sbjct: 307 TGKSVAILNDAEASYIQSHKNQMEHTQLTFKENRDMLKQSVDLSNKQVATANSQASYNAQ 366 Query: 419 VLNGSDPKSRFYDAVSVASNLSPTALFGKF-----------------NEEYNFYKQQQ-- 459 S +++ + S N++ L G F N +YN QQ Sbjct: 367 FAVDSANINQWTEGASGILNVAGNLLTGNFGGALGGLASGGMKVFNANRDYNDKVVQQGF 426 Query: 460 -------------------------------AEYKDLALQPPSVTESEMGNAFQIANSIN 488 A DL QP SV + AFQ N + Sbjct: 427 TSENNALKSQSNALANMKSKIALDQSIRAYNATMADLQNQPISVQQIGNDLAFQSGNRLT 486 Query: 489 GLTMKISVPSPKEITFLQKYYMLFGFEVNDY-NSFIEPINSMTVCNYLKCTGTY--TIRD 545 + K+S+ + + +Y +G VN + N + + S NY+K T+R Sbjct: 487 DVYWKVSLAQKEIMGRANEYIKCYGVLVNWFTNDALSVMRSRKRFNYIKMINVNLGTLR- 545 Query: 546 IDPMLMEQLKAILESGVRFWH 566 + M ++AI +SGVR W+ Sbjct: 546 ANQSHMNAIQAIFQSGVRIWN 566 WO 00/32825 PCT/IB99/02040 294 Query= pt|110875 44AHJDORFO05 Phage 44AHJD ORF |12643-138901-1 1 (415 letters) >gil3845203 (AE001399) GAF domain protein (cyclic nt signal transduct.) (Plasmodium falciparum] Length = 1245 Score = 52.3 bits (123), Expect = 6e-06 Identities = 59/246 (23%), Positives = 105/246 (41%), Gaps = 27/246 (10%) Query: 174 ESIDRNHGNVDYIGFPKMFLLGNAVNFSSPILSNLNIYNLLQKHKMNTSRLYKNIFLEMR 233 +S D N+ N + + N+V FS+ N IY++L N +YK + E+ Sbjct: 854 DSSDNNNNNNNNNNNNNNYNNNNSVIFST---- NEKIYDML-----NRDNIYKKVKKEIF 904 Query: 234 RNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYNLADDNLRNHINQNGDFFYIKTDDKYI-- 291 D + + + +N + M + N N ++N+ N+ N NGD Y KY Sbjct: 905 EGDSIIKTMENKPNLTNKNYMNNDNIDNNNNNNNNNNIDNNNNNNGDNIYNDDLKKYYLN 964 Query: 292 KVMYNVTTFMTNIIVVPYTKQYEFCTKIR-DIDNHVTYLRDDMFYKENMERYYYNPSNLH 350 ++N +++ + + K E K+ I + L +F+K NM + + L+ Sbjct: 965 TSIFNKDLYVKHFVDIIMNKSLEEIIKMNVYISERINSL---LFHKGNM---LNDVTKLY 1018 Query: 351 FDNAYSKNYVVDNDRYLYLDMNKIIKFHIKNEMKKNMSEFERKEKIYEDN----YIENTK 406 NAY + N K I F + E K +M F+ +KIY+ N + N K Sbjct: 1019 MSNAYGEKCFFFN-----FPQIKEIIFVNEYEKKMDMKYFKMLKKIYKYNLNKIFSNNYK 1073 Query: 407 KYLMKQ 412 +++ K+ Sbjct: 1074 FFIIKK 1079 >gil3758843IembjCAB11128.11 (Z98551) predicted using hexExon; MAL3P6.23 (PFC0820w), Hypothetical protein, len: 4982 aa [Plasmodium falciparum] Length = 4981 Score = 49.2 bits (115), Expect = Se-05 Identities = 67/287 (23%), Positives = 110/287 (37%), Gaps = 60/287 (20%) Query: 127 ITDLNSATDLKYHSNFLKHYPIIIYDEFLALEDDYLIDEWDKLKT----IYESIDRNHGN 182 I D+N + D+ + +++ I YD +++DK++ IY +ID++ N Sbjct: 3619 IMDINKSKDISKNMEIVQN --- IEYD ----------- -NKYDKIRNDMDAIYMAIDKDMDN 3664 Query: 183 VDYIGFPKMFLLGNAVNFSSPILSNLNIYNL ---- LQKHKMNTSRLYKNIFLEMRRNDYV 238 + I + F L N S +N YNL ++ K N R Y N F +D Sbjct: 3665 IGIINCMRYFNLYKNYNNLSNECNNRE-YNLNELYMEDIKRNMKR-YDNNFNINHYDDNN 3722 Query: 239 NEKRNTRAFNSNDDAMTTGEFEFNEYNLADDNLRNHINQNGDFFYIKTDDKYIKVMYNVT 298 N N N+N++ N N ++N N+ N NG F+ D Sbjct: 3723 N NGGCFFFHVD------------ 3771 Query: 299 TFMTNIIVVPYTKQYEFCTKIRDIDNHVTYLRDDMFYKENMERYYYNPSNLHFDNAYSKN 358 K FCTK ++F +N+E N N N Y+ N Sbjct: 3772 ------------ KDLFFCTK------------KNIFPCKNIETVCKNEYNKKIYNNYTCN 3807 Query: 359 YVVDNDRYLYLDMNKIIKFHIKNEMKKNMSEFERKEK-IYEDNYIEN 404 V+N + ++IK + + N E+ + EK +Y + EN Sbjct: 3808 ISVNNTLNCLNIIKELIKLNNNKKKILNYYEYHKVEKLLYYRHSFEN 3854 Score = 35.6 bits (80), Expect = 0.70 Identities = 62/290 (21%), Positives = 121/290 (41%), Gaps = 65/290 (22%) Query: 2 VKQNRLDMVRDYQNAVN--HVRKKIPDKYNQIELVDELMNDDIDYYISISNRSDGKSFNY 59 +K+N ++ +N +N +V++ DK N I D++I+ SN + +SF Sbjct: 4445 IKRNNINKSNIKRNNINKSNVKRSNTDKSNVIS----------DFHIT-SNNNITRSFT- 4492 Query: 60 VSFFIYLAIKLDIKFTLLSRHYTLRDAYRDFIEEIIDENPLFKSKRVTFR$ARDYLAIIY 119 A D F LS TL +Y +F + + I Sbjct: 4493 ------- ATLTDSIFNTLSE--TLNYSYDNFFSNMDN--------------------IKI 4523 Query: 120 QDKEIGVITDLNSATDLKYHSNFLKHYPIIIYDEFL-----ALEDDYLIDEWDKLKTIYE 174 + El ITD++ +YH N+LK + +E++ + +D + DE ++T+ E Sbjct: 4524 KKNEINNITDVDYGNKKEYHENYLKVKQNKVNEEYIEETFKSDKDCSIKDEACTIRTLSE 4583 WO 00/32825 PCT/IB99/02040 295 Query: 175 S--IDRNHGNVDYIGFPKMFLLGNAVNFSSPILSNLNIYNLLQKHKMN--TSRLYKNIFL 230 S I N N+D + + + S P N++ N ++K+ +N R+ KN Sbjct: 4584 SCNISENISNID---------MDDEDHISFPNGRNVHDNNYMKKNHVNYDKMRVGKNKIP 4634 Query: 231 EMRRNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYNLADDNLRNHINQNGD 280 D + +++ + +D M++ ++ E ++ + L + NG+ Sbjct: 4635 SFTHFDKILDEKKKK----SDKDMSSSKWLEREEHIKEIKLEKNEYMNGN 4680 Score = 34.0 bits (76), Expect = 2.0 Identities = 47/211 (22%), Positives = 84/211 (39%), Gaps = 32/211 (15%) Query: 210 IYNLLQKHKMNTSRLYKNIFLEMRRNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYNLADD 269 I++LLQK LY+N+ + R + N+ T E ++ + ++ Sbjct: 918 IFSLLQKDSSPLLVLYENVHI-----------REGEKYGRNE--ATDNEVDYKKGDIIKH 964 Query: 270 NLRNHINQNGDFFYIKTD---DKYIKVMYNVTTFMTNIIVVPYTKQYEFCTKIRDIDNHV 326 N+ N + D + D+ K MY + V E K D+ N+ Sbjct: 965 NVTNEHGNHSDSYPYGNSLNLDRKPKNMYE-DIYKEKGFVKSDCSNIEI--KKNDMINND 1021 Query: 327 TYLRDDMFYKENMERYYYNPSNLHFDNAYSKNYVVDNDRYLYLDMNKII---- KFHIKNE 382 Y +++ FY+++ Y+ + YV++ +YL +N ++ F +KN+ Sbjct: 1022 VYKKNE-FYEDSRINMIYDEDEIKTWFLIPHKYVIN---IIYLFLNILLTDESNFKLKNK 1077 Query: 383 MKKNMSEFERKEKIYEDN-----YIENTKKY 408 E K IYEDN ++N KKY Sbjct: 1078 KYGYFVNEETKGTIYEDNNGLQEILKNGKKY 1108 Score = 33.6 bits (75), Expect = 2.7 Identities = 42/198 (21%), Positives = 77/198 (38%), Gaps = 42/198 (21%) Query: 222 SRLYKNIFLEMR - -- RNDYVNEKRNTRAF ----------- -NSNDDAMTTGEFEFNEYNLA 267 S LY I++ + +N + K+NT + N+++D TT E + + Sbjct: 411 SVLYSIIYMNKKYKKKNFIITNKKNTNVYFENDVIQLSVENTSEDTFTTNTRESSLNSGM 470 Query: 268 DDNLRNHINQNGDFFYIKTDDKYIKVMYNVTTFMTNIIVVPYTKQYEFCTKIRDIDNHVT 327 +++R +N D +DDK ++Y N YTK E Sbj ct: 471 MNDMRYSVNNYADEKVYHSDDKSDHLIYKHVHDEKNKYDEMYTKTKE ------------- -517 Query: 328 YLRDDMFYKENMERYYYNPSNLHFDNAYSKNYVVDNDRYLYLDMNKIIKFHIKNEMKKNM 387 +++ YK N+ + N K LD+ K I H+KN+ + N Sbjct: 518 --NENIIYKSNIVDKKTCDISSEMVNGKDK-----------LDVEKYIGSHVKND-ENNK 563 Query: 388 SEFERK-EKIYEDNYIEN 404 + ++K + + + YI+N Sbjct: 564 EKLKKKIDNVNKKEYIDN 581 >gil3845297 (AE001421) hypothetical protein (Plasmodium falciparum] Length = 2380 Score = 48.0 bits (112), Expect = le-04 Identities = 87/390 (22%), Positives = 160/390 (40%), Gaps = 65/390 (16%) Query: 20 VRKKIPDKYNQIELVDELMNDDIDYYISISNRSDGKSFNYVSFF-----IYLAIKLDIKF 74 +++K +K ++ + +N D + ++ R K+ NY++ +YL I DI Sbjct: 1049 LQRKNMNKCSKNRNRNRYINKDSNIHLMNLIRIKFKNLNYMNMNSFEIELYLKINNDIFL 1108 Query: 75 TLLSRHYTLRDAYR------DFIEEIIDEN-PLFKSKRVTFRSARDYLAIIYQDKEIGVI 127 +Y +++ Y + + + EN + +++ ++ + Y +K+ Sbjct: 1109 QFNKHNYNVQNFYNFSITLINIMSKYYSENFYAYNLEKIVYKFLLNNKNFEYIEKQYSSK 1168 Query: 128 TDLNSATDLKYHSNFLKHYPIIIYDEFLA ---- LEDDYLIDEWDKLKTIYESIDRNHGNV 183 D+N D+ ++ +K+ II EFL L+ D I + KLKT ++ Sbjct: 1169 EDMNEL-DILVNTYDMKYDKII---EFLKNNGYLKIDRYIYFYPKLKT----------DI 1214 Query: 184 DYIGFPKMFLLGNAVNFSSPILSNLNIYNLLQKHKMNTSRLY------KNIF--LEMRRN 235 F ++FL N + L NI +++ K + Y K IF + M+ + Sbjct: 1215 ILFFFKEIFLNDNILKIDRKFLKK-NITIMIEVLKEIFFKEYVKRCITKVIFFPVHMKEH 1273 Query: 236 DYVNEKR--------NTRAFNSNDDAMTTGEFEFNEYNLADDNLRNHINQNGDFFYIKTD 287 D+V K N+ FN+ D + N YN D+ N+ N N +Y K WO 00/32825 PCT/IB99/02040 296 Sbjct: 1274 DHVMNKNYYNNQYVNNSNMFNTRGDHNNNNQTNDNHYNHHYDDTHNNNNNNNSKYY-KNK 1332 Query: 288 DKYIKVMYNVTTFMTNIIV---VPYTKQYEFCTKIRDIDNHVTYLRDDMFYKEN ---- ME 340 +K K+MY +++ + V K + K I + Y+ ++ N + Sbjct: 1333 NKN-KIMYEKERKSSSLFISNNVQDVKPIKHYLKYSSIYKNFIYIISEIKNFNNKITKIN 1391 Query: 341 RY-YYNPSNLHFDNAYSKNYVVDNDRYLYL 369 RY YYN NL+ D+ ND YL+L Sbjct: 1392 RYNYYNYMNLNIDDL--------NDAYLFL 1413 Score = 32.5 bits (72), Expect = 6.0 Identities = 46/183 (25%), Positives = 73/183 (39%), Gaps = 26/183 (14%) Query: 225 YKNIFLEMRRNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYNLADDNLRNHINQNGDFFYI 284 +KNI ++ ++N + NSN + + N N+ +N N IN + I Sbj ct: 27 HKNINKNIKNKKFINIDNSNNCNNSNSNNSNSNNNNNNNNNIVRNN-NNFINADKKKNVI 85 Query: 285 KTDDKYIKVMYNVTTFMTNIIVVPYTKQYEFCTKIRDIDNHVTYLRDDMFYKENMERYYY 344 +D IK V NI Y ++ + D+ N+ + + KE ER Sbjct: 86 LNEDDDIKNKELVDESFVNIFF--YENYFKNLFNLNDVSNNKVI--NIIEQKEGDER--- 138 Query: 345 NPSNLHFDNAYSKNYVVDNDRYLYLDMNKIIKFHIKNEMKKNMSEFERKEKIYEDNYIEN 404 N N N +KN V DN +NK IKN +N++E Y N++ + Sbjct: 139 NADN --- -NLKNKNIVRDN ------- INK ----- IKN--TRNVNEILIYNNKYIINFLND 180 Query: 405 TKK 407 T K Sbjct: 181 TTK 183 >gil4493936|emb|CAB38972.1| (AL034556) predicted using hexExon; MAL3P5.6 (PFC0600w), Hypothetical protein, len: 250 aa [Plasmodium falciparum] Length = 249 Score = 47.3 bits (110), Expect = 2e-04 Identities = 53/215 (24%), Positives = 87/215 (39%), Gaps = 30/215 (13%) Query: 209 NIYNLLQKHKMNTSRLYKNIFLEMRRNDYVNEKRNTRAFNSNDDAMTTGEFEF--NEYNL 266 NIYN L++ YKN N ++ +N N+N EFE N YN Sbjct: 13 NIYNKLEEK-------YKNFLKLKNMNSHMGASQNMNV-NNNYTMNELEEFEKINNNYNN 64 Query: 267 ADDNLRNHINQNGDFFYIKTD-----DKYIKVMYNVTTFMTNIIVVPYTKQYEFCTKIRD 321 ++N+ N+IN D+ IK +K ++ YN + I T +++ Sbj ct: 65 NNNNINNNINNYYDYMNIKVSQSVQHNKRLQDFYNNKNSFQHYIKKLKTCRFDADDIRNL 124 Query: 322 IDNHVTYLRDDMFYK-----ENMERYYYNPSNLHFDNAYSKNYVVDNDRYLYLDMNKIIK 376 ++ + Y RD+ K EN + N + N+ S NY DN+ LY +N++ K Sbjct: 125 LEKRLAYERDNTLIKNIQEEENKKGIGINGNFGSESNSSSSNY--DNNYLLYRKINRLNK 182 Query: 377 FHIKNEMKKNMSEFERKEKIYEDNYIENTKKYLMK 411 + ++ KI KKY++K Sbjct: 183 TNTNKSKNRSRKRKRINSKI--------DKKYIIK 209 >gi|3845165 (AE001390) hypothetical protein {Plasmodium falciparum] Length = 1247 Score = 45.7 bits (106), Expect = 6e-04 Identities = 52/239 (21%), Positives = 94/239 (38%), Gaps = 38/239 (15%) Query: 206 SNLNIYNLLQKHKMNTSRLYKNIFLEMRRNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYN 265 +N N +N ++K K R I +N + +N ++N+D E N N Sbjct: 474 NNTNKWNEIKKRKKKFKREKNKIINNSFQNQEAEDDKNNNNNDNNNDNHNDNNNENNNEN 533 Query: 266 LADDNLRNHINQNGDFFYI-KTDDKYIK----VMYNVTTFMTNIIVVPYTKQYEFCTKIR 320 D+N N+ + N D I D+ Y +YN T ++ YTK + + + Sbjct: 534 NNDNNNENNNDINNDINNIHNNDNNYYNNDNINLYNEMTKKKCMLDNSYTKYFFYIFTL- 592 Query: 321 DIDNHVTYLRDDMFYKENME--------RYYYN-----------------PSNLHFDNAYS 356 + + ++ + FY++N + ++YYN + N Sbjct: 593 --- DMLPSIKFETFYEKNTDHKNFNENYKFYYNTDDDTDIINAIKKKNVKNKKKNGNIVI 649 Query: 357 KNYVVDNDRYLYLDMNKIIKFHIKNEMKKNMSEFER ----KEKIYEDNYIENTKKYLMK 411 KNY+ N+ Y YL+ N+ + I + K +E K+ I+ ++Y E K K WO 00/32825 PCT/IB99/02040 297 Sbjct: 650 KNYINHNE-YSYLEYNENKNYEINKKEKLLTENYEYDMYIKDNIHDYSEGDGKQTK 707 Score = 41.0 bits (94), Expect = 0.016 Identities = 58/245 (23%), Positives = 96/245 (38%), Gaps = 43/245 (17%) Query: 207 NLNIYNLLQKHKMNTSRLYKNIFLEMRRNDYVNEKRNTRAFNSNDDAMTTGEFEFNEYNL 266 N+N+YN + K K Y F + D + + + N D E YN Sbjct: 564 NINLYNEMTKKKCMLDNSYTKYFFYIFTLDMLPSIKFETFYEKNTDHKNFNENYKFYYNT 623 Query: 267 ADD----------NLRNHINQNGDFF---YIKTDDKYIKVMYNVT-TFMTNIIVVPYTKQ 312 DD N++N +NG+ YI ++ Y + YN + N T+ Sbjct: 624 DDDTDIINAIKKKNVKNK-KKNGNIVIKNYINHNE-YSYLEYNENKNYEINKKEKLLTEN 681 Query: 313 YEFCTKIRDIDNHVTYLRDDMFYKENMERYYYNPSNLHFDNAYSK -------- -NYV--VD 362 YE+ I+D ++ Y D + + YN +N +N Y K +Y+ VD Sbjct: 682 YEYDMYIKDNIHYNDYSEGDGKQTKKASSFLYNNNN ---NNKYKKEDNKTQIISYMDHVD 738 Query: 363 NDR---------YLYLDMNKIIKFHIK-NEM----KKNMSEFERKEKIYEDNYIENTKKY 408 N+ Y + +++ F +K N+M K+ F +E I + +EN K+ Sbjct: 739 NENGVKGLKKRNLFYNNSDQLYNFDVKDNDMIKYEKRQSKNFVEEEFINGNRKMENEDKH 798 Query: 409 LMKQY 413 L K Y Sbjct: 799 LKKHY 803 Query= pt1110877 44AHJDORFOO7 Phage 44AHJD ORF 12044-302711 1 (327 letters) >gil11819601embICAA87731.1 (Z47794) connector protein [Bacteriophage CP-1] Length = 337 Score = 45.7 bits (106), Expect = Se-04 Identities = 44/184 (23%), Positives = 84/184 (44%), Gaps = 13/184 (7%) Query: 127 QIHKLYDNCMSGNFVVMQNKPIQYNSDIEIIEHYTDELAEVALSRFSLIMQAKFSK--IF 184 ++HK + + +V+ N Y I +E + ++LA++ L+ L A+ + IF Sbjct: 125 ELHKDNPDKIKRPCIVIPNNNF-YEPYIGYLELFCEKLADIELT-IQLNRNAQITPYFIF 182 Query: 185 KSEINDESINQLVSEIYNGAPFVKMSPMFNAD--------DDIIDLTSNSVIPALTEMKR 236 N S+ + ++I N P V ++ + D D I + L ++ Sbjct: 183 ADNTNVLSMKNIFNKIANFEPVVYLNKQKDQDGQDSFKQLSDYIQVFRTDAPFLLDKLHD 242 Query: 237 EYQNKISELSNYLGINSLAVDKESGVSDEEAKSNRGFTTSNSNIYLKGREP-ITFLSKRY 295 E +.L ++GIN+ DK+ + EA SN G ++N + K R + ++K Y Sbjct: 243 EKLRVMNQLLTFIGINNNPSDKKERLVVSEAISNNGVISANIEVGWKSRRKFVELINKCY 302 Query: 296 GLDI 299 GL+I Sbjct: 303 GLEI 306 >gi|1429239iembICAA67658| (X99260) upper collar protein [Bacteriophage B103] Length = 308 Score = 44.9 bits (104), Expect = 8e-04 Identities = 40/159 (25%), Positives = 73/159 (45%), Gaps = 11/159 (6%) Query: 150 YNSDIEI-----IEHYTDELAEVA-LSRFSLIMQAKFSKIFKSEINDESINQLVSEIYNG 203 YN+D++ +E + +LAE+ + + Q I ++ N S+ + ++ Sbjct: 121 YNNDLKCSTLPALEMFAQDLAELKEIIAVNQNAQKTPVLIAANDNNQLSLKNIYNQYEGN 180 Query: 204 APFVKMSPMFNADD-DIIDLTSNSVIPALTEMKREYQNKISELSNYLGINSLAVDKESGV 262 AP + + + D+ + + V+ L K N E+ YLGI + ++K+ + Sbj ct: 181 APVIFVHESLDLDNLKVFKTDAPYVVDKLNAQKNAVWN --- EVMTYLGIKNANLEKKERM 237 Query: 263 SDEEAKSNRGFTTSNSNIYLKGR-EPITFLSKRYGLDIK 300 E SN S+ NIYLK R E +S+ YGL++K Sbjct: 238 VTSEVDSNDEQIESSGNIYLKARQEACNKISELYGLNLK 276 >gil137915|splP07535|VG10_BPPZA UPPER COLLAR PROTEIN (CONNECTOR PROTEIN) (LATE PROTEIN GP10) >gij75851|pir||WMBP10 gene WO 00/32825 PCT/IB99/02040 298 10 protein - phage PZA >gil216059 (M11813) upper collar protein (Bacteriophage PZA) Length = 309 Score = 43.8 bits (101), Expect = 0.002 Identities = 38/160 (23%), Positives = 75/160 (46%), Gaps = 13/160 (8%) Query: 150 YNSDIEI-----IEHYTDELAEVALSRFSLIMQAKFSKIF--KSEINDESINQLVSEIYN 202 YN+D+ +E + ELAE+ S+ A+ + + ++ N S+ Q+ ++ Sbjct: 122 YNNDMSFPTTPTLELFAAELAELK-EIISVNQNAQKTPVLIRANDNNQLSLKQVYNQYEG 180 Query: 203 GAPFVKMSPMFNADD-DIIDLTSNSVIPALTEMKREYQNKISELSNYLGINSLAVDKESG 261 AP + ++D ++ + V+ L K N E+ +LGI + ++K+ Sbjct: 181 NAPVIFAHEALDSDSIEVFKTDAPYVVDKLNAQKNAVWN---EMMTFLGIKNANLEKKER 237 Query: 262 VSDEEAKSNRGFTTSNSNIYLKGR-EPITFLSKRYGLDIK 300 + +E SN S+ ++LK R E +++ YGLD+K Sbjct: 238 MVTDEVSSNDEQIESSGTVFLKSREEACEKINELYGLDVK 277 >gil137914IspIP04332|VG10_BPPH2 UPPER COLLAR PROTEIN (CONNECTOR PROTEIN) (LATE PROTEIN GP10) >gi|75852|pir||WMBPC9 gene 10 protein - phage phi-29 >giJ215328 (M14782) upper collar protein (Bacteriophage phi-29] >gil215340 (M12456) p10 connector protein (Bacteriophage phi-29] >gil224161jprf|11011232A protein p10,connector [Bacteriophage phi-29] >gil225365|prf|11301270E gene 10 (Bacteriophage phi-29) Length = 309 Score = 41.4 bits (95), Expect = 0.009 Identities = 37/160 (23%), Positives = 75/160 (46%), Gaps = 13/160 (8%) Query: 150 YNSDIEI-----IEHYTDELAEVALSRFSLIMQAKFSKIF--KSEINDESINQLVSEIYN 202 YN+D+ +E + ELAE+ S+ A+ + + ++ N S+ Q+ ++ Sbjct: 122 YNNDMAFPTTPTLELFAAELAELK-EIISVNQNAQKTPVLIRANDNNQLSLKQVYNQYEG 180 Query: 203 GAPFVKMSPMFNADD-DIIDLTSNSVIPALTEMKREYQNKISELSNYLGINSLAVDKESG 261 AP + ++D ++ + V+ L K N E+ +LGI + ++K+ Sbjct: 181 NAPVIFAHEALDSDSIEVFKTDAPYVVDKLNAQKNAVWN---EMMTFLGIKNANLEKKER 237 Query: 262 VSDEEAKSNRGFTTSNSNIYLKGR-EPITFLSKRYGLDIK 300 + +E SN S+ ++LK R E +++ YGL++K Sbjct: 238 MVTDEVSSNDEQIESSGTVFLKSREEACEKINELYGLNVK 277 Query= pt|110878 44AHJDORFOO8 Phage 44AHJD ORF 13020-377512 1 (251 letters) >gil4982468|gb|AAD30963.2 (AF118151) SNF1/AMP-activated kinase (Dictyostelium discoideum] Length = 718 Score = 52.3 bits (123), Expect = 3e-06 Identities = 28/118 (23%), Positives = 56/118 (46%), Gaps = 5/118 (4%) Query: 121 YLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYV ---- -SLPQSEVNIDVDN 176 + + GF N ++ SN + +N N + N+ T N N + ++ + +N + +N Sbjct: 382 FTTTTGFNPTNSNSISNNNNNNNNNNNNTTNNNNNTTNNNNSIINNNNINNNNINNNNNN 441 Query: 177 TTLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLID-NIDKAYD 233 +NN I+N N ++N +N N N N N+ + T+ + I N++ +Y+ Sbjct: 442 NNNNINNNNIINNNNNNNNNNNNNNNNNNNNNNNNSSISGGTEVFSISPNLNNSYN 499 Score = 37.5 bits (85), Expect = 0.094 Identities = 17/111 (15%), Positives = 45/111 (40%) Query: 130 HNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDN 189 +N + +N + +N N + +N++ ++ + P + + +++ - N+ ++ - - Sbjct: 456 NNNNNNNNNNNeaNNNNNNNNSSISGGTEVFSISPNLNNSYNSNSSGNSNGSNSNNNS 515 Query: 190 GKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKKILN 240 N +N +N N N N N ID+++ + + + N Sbjct: 516 NNNTNNDNNNNNNNNNNNNNNNNNNNNNNNN CIDSVNNSLNNENDVNN 566 WO 00/32825 PCT/IB99/02040 299 Score = 32.8 bits (73), Expect = 2.4 Identities = 31/140 (22%), Positives = 57/140 (40%), Gaps = 14/140 (10%) Query: 109 LNVVYSSSEVEKYLQSQGFTEHNEDTTS---NTDETSNQNATSLDNSTGMTANRNAYVSL 165 LN Y+S+ S N +T + N + +N N + +N+ N N + Sbjct: 494 LNNSYNSNSSGNSNGSNSNNNSNNNTNNDN CIDS 553 Query: 166 PQSEVN--IDVDNTTLRFADNNTIDNGKTVNKSS -------- -NESNQNAKRNQNQKGNAK 215 + +N DV+N+ + +NN D+G N ++ N N + N GN Sbj ct: 554 VNNSLNNENDVNNSNINNNNNNNSDDGSNNNSYEGGGDVLLLSDLNGNNQLGGNDNGNVV 613 Query: 216 GTQFTKQYLIDNIDKAYDLR 235 Q L++++D D++ Sbjct: 614 NLNNNFQ-LLNSLDLNSDIQ 632 Score = 31.7 bits (70), Expect = 5.4 Identities = 25/115 (21%), Positives = 48/115 (41%), Gaps = 10/115 (8%) Query: 130 HNEDTTSNTDETSNQNATSLDNST--- GMTAN-RNAYVSLPQSEVNIDVDNTTLRFADNN 185 +N + +N + +N N +S+ T ++ N N+Y S S N + N+ +N Sbjct: 462 NNNNNNNNNNNNNNNNNSSISGGTEVFSISPNLNNSYNS--NSSGNSNGSNSNNNSNNNT 519 Query: 186 TIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKKILN 240 DN N ++N +N N N N N +++++ D+ +N Sbjct: 520 NNDN----NNNNNNNNNNNNNNNNNNNNNNCIDSVNNSLNNENDVNNSNIN 570 Score = 31.7 bits (70), Expect = 5.4 Identities = 15/104 (14%), Positives = 43/104 (40%) Query: 110 NVVYSSSEVEKYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSE 169 N+ +++ + + +N + +N + +N N + +N+ + + V Sbjct: 434 NINNNUNNNNNINNNNIINNNNNNNNNNNNNNNNNNNNNNNNNNSSISGGTEVFSISPN 493 Query: 170 VNIDVDNTTLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGN 213 +N ++ + ++ + +N N +++ +N N UN N Sbjct: 494 LNNSYNSNSSGNSNGSNSNNNSNNNTNNDNNNNNNNNNNNNNNN 537 Score = 30.9 bits (68), Expect = 9.2 Identities = 16/84 (19%), Positives = 34/84 (40%) Query: 130 HNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDN 189 +N + +N + +N N + +N+ + S+ + N N++ +N+ +N Sbjct: 455 NNNNNNNNNNNNNNUNNNNNNSSISGGTEVFSISPNLNNSYNSNSSGNSNGSNSNNN 514 Query: 190 GKTVNKSSNESNQNAKRNQNQKGN 213 + N +N N N N N Sbjct: 515 SNNNTNNDNNNNNNNNNNNNNNNN 538 >gil17300771sp|P181601KYK1_DICDI NON-RECEPTOR TYROSINE KINASE SPORE LYSIS A (TYROSINE-PROTEIN KINASE 1) >gil974334 (U32174) non-receptor tyrosine kinase [Dictyostelium discoideum] Length = 1584 Score = 46.5 bits (108), Expect = 2e-04 Identities = 29/106 (27%), Positives = 48/106 (44%), Gaps = 4/106 (3%) Query: 130 HNEDTTSUTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNID --- VDNTTLRFADN-N 185 +NED +SN + +N N ++N+ N N + + N + ++NTT N N Sbjct: 442 NNEDISSNN SNSSNTNNNNINNTTNNNNSNSN 501 Query: 186 TIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKA 231 +N N +SN +N N N N TK+ I + D++ Sbjct: 502 NNNNNNNNSNSNSNNNNINNNNNNNNNNNNIYLTKKPSIGSTDES 547 Score = 34.0 bits (76), Expect = 1.1 Identities = 20/117 (17%), Positives = 46/117 (39%) Query: 87 NRQTVEAFGMQVITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNEDTTSUTDETSNQNA 146 N G IT T + + ++ ++ + +N + +N + +N N WO 00/32825 PCT/IB99/02040 300 Sbjct: 415 NNNNNNIIGNGKITTTTTTSTSPSSINNNEDISSNNN NNNNNNNNN 474 Query: 147 TSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNGKTVNKSSNESNQN 203 +++++ T N N + + N + +N N+ +N N ++N +N N Sbjct: 475 NNNNSNSSNTNNNNINNTTNNNNSNSNNNNNNNNSNSNSNSNNNNINNNNNNNNNNN 531 Score = 33.2 bits (74), Expect = 1.8 Identities = 18/88 (20%), Positives = 35/88 (39%) Query: 130 HNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDN 189 +N + ++N + +N N T T + S+ +E +N +NN +N Sbjct: 405 NNNNNSNNNNNNNNNNIIGNGKITTTTTTSTSPSSINNNEDISSNNNNNNNNNNNNNNNN 464 Query: 190 GKTVNKSSNESNQNAKRNQNQKGNAKGT 217 N ++N +N N+ + N T Sbjct: 465 NNNNNNNNNNNNNNSNSSNTNNNNINNT 492 Score = 32.5 bits (72), Expect = 3.1 Identities = 18/94 (19%), Positives = 37/94 (39%) Query: 120 KYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTL 179 K + S N + +N++ +N N ++ + +T S N D+ + Sbjct: 392 KNVNSTSILVPNGNNNNNSNNNNNNNNNNIIGNGKITTTTTTSTSPSSINNNEDISSNNN 451 Query: 180 RFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGN 213 +NN +N N ++N +N N + + N Sbjct: 452 NN SNSSNTN 485 Score = 32.5 bits (72), Expect = 3.1 Identities = 24/110 (21%), Positives = 44/110 (39%), Gaps = 10/110 (9%) Query: 138 TDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNGK------ 191 T T++ + +S++N+ +++N N + + N + +N +NN N Sbjct: 429 TTTTTSTSPSSINNNEDISSN SNSSNTNNNN 488 Query: 192 ----TVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKK 237 T N +SN +NN N N N+ +N + L KK Sbjct: 489 INNTTNNNNSNSNNNNNNNNSNSNSNSNNNNINNNNNNNNNNNNIYLTKK 538 >gi|3758855|embICAB11140.1 (Z98551) predicted using hexExon; MAL3P6.11 (PFC0760c), Hypothetical protein, len: 3395 aa (Plasmodium falciparum] Length = 3394 Score = 46.5 bits (108), Expect = 2e-04 Identities = 52/202 (25%), Positives = 96/202 (46%), Gaps = 32/202 (15%) Query: 21 FNEFVNDNKLTFYDDEFQFMQKMLKFD-KDVLAIVNEKVFKGFSLKDELSDL--LFKKSF 77 F ++ ++ K T D+ M+K K D DV + NEK++ L ++L+ + + KK Sbjct: 665 FEKYCSNIKNTLIRDD---MKKFRKPDISDVHILHNEKIYLEKLLNEKLNYIKDIEKKLD 721 Query: 78 TIHFLDREINRQTVEAFGMQV-----ITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNE 132 +H + IN+ + + +QV I V + DY + S + + K + +N Sbjct: 722 ELHGV--- INKNKEDIYILQVEKQTLIKVISSVYDYTKME-SENHIFKMNTTWNKMLNNV 777 Query: 133 DTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNGKT 192 +SN D +NQN +++N+ + N+N N +++N + N +N Sbjct: 778 HMSSNKDY-NNQNNQNIENNQNIENNQN----------NQNIEN------NQNIENNQNN 820 Query: 193 VNKSSNESNQNAKRNQNQKGNA 214 N +N++NQN + NQN + NA Sbjct: 821 QNNQNNQNNQENQEEQNNQNNA 842 Score = 33.6 bits (75), Expect = 1.4 Identities = 46/221 (20%), Positives = 89/221 (39%), Gaps = 37/221 (16%) - Query: 10 DFIKSELIKKGFNEFVNDNKLTFYDDEFQFMQKMLKFDKDVLAIVNEKVFKGFSLKDELS 69 D +K E K N + +L Y + + M+K K + V K SL Sbjct: 367 DSLKIEYNKSKTNIQQLNEQLVNYKNFIKEMEKKYK----------QLVVKNNSLFSITH 416 Query: 70 DLLFKKSFTIHFLDREINRQTVEAFGMQVITVCITH--- EDYLNVVYSSSEVEKYLQSQG 126 WO 00/32825 PCT/IB99/02040 301 D + K+ I + R + ++ + I H +D+L+V+Y + + L + Sbjct: 417 DFINLKNSNIIIIRRTSDMKQI----FKMYNLDIEHFNEQDHLSVIY----IYEILYNTN 468 Query: 127 FTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNT 186 +N D +N D +N N + +N+ N N N + +N + Sbj ct: 469 -DNNNNDNDNNNDNNNNNNNNNDNNNNNNNDNNNN--------- -NNNYNNIMM ------ M 512 Query: 187 IDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDN 227 I+N + N ++ + N + N N + N ++ +Y I+N Sbjct: 513 IENMNSGNHPNSNNLHNYRHNTNDENNLSSLKTSFRYKINN 553 Score = 32.8 bits (73), Expect = 2.4 Identities = 28/122 (22%), Positives = 53/122 (42%), Gaps = 2/122 (1%) Query: 119 EKYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNID-VDNT 177 E Y S + +++ N + +N + + DN+ N N ++ +N D ++N Sbj ct: 2838 ENYPVSTHYDNNDDINKDNINNDNNNDNINDDNNNDNINNDNNNDNINNDNINNDNINND 2897 Query: 178 TLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKK 237 +N+ +NG SSN ++ N N N K N +G + + + + YD K Sbjct: 2898 NNNDNNNDNSNNGFVCELSSNINDFNNILNVN-KDNFQGINKSNNFSTNLSEYNYDAYVK 2956 Query: 238 IL 239 I+ Sbjct: 2957 IV 2958 Score = 32.5 bits (72), Expect = 3.1 Identities = 46/249 (18%), Positives = 101/249 (40%), Gaps = 31/249 (12%) Query: 9 YDFIKSELIKKGFNEFVNDNKLTFYDDEFQFMQKMLKFDKDVLAIVNEKVFKGFSLKDEL 68 Y+++K ++ N N NK E Q++ K+ + + + +E K L++ Sbjct: 2150 YNYVK---VQNATNREDNKNK------ERNLSQEIYKYINENIDLTSELEKKNDMLENYK 2200 Query: 69 SDL------LFKKSFTIHFLDREINRQTVEAFGMQVITVCITHEDYLNVVYSSSEVEKYL 122 ++L ++K + I L + M+ + + N + E+ + L Sbjct: 2201 NELKEKNEEIYKLNNDIDMLSNNCKKLKESIMMMEKYKIIMN-----NNIQEKDEIIENL 2255 Query: 123 QSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTAN ---- RNAYVSLPQSE ---- VNIDV 174 +++ + +D +N + ++S M+ + N + +L +S N+D+ Sbjct: 2256 KNK-YNNKLDDLINNYSVVDKSIVSCFEDSNIMSPSCNDILNVFNNLSKSNKKVCTNMDI 2314 Query: 175 DNTTLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDL 234 N + ++I+N +N +N +NN N N N K YL++N+ D Sbjct: 2315 CNENMDSI--SSINNVNNINNVNNINNVNNINNVNNINNVKNIVDINNYLVNNLQLNKDN 2372 Query: 235 RKKILNEFD 243 I+ +F+ Sbjct: 2373 DNIIIIKFN 2381 Score = 32.1 bits (71), Expect = 4.1 Identities = 20/103 (19%), Positives = 48/103 (46%), Gaps = 2/103 (1%) Query: 115 SSEVEKYLQSQGFTEENEDTTSNTDETSNQN--ATSLDNSTGMTANRNAYVSLPQSEVNI 172 +++ EKY EH + N D +N+N L ++ ++ + N S ++E+ Sbjct: 3264 NNDEEKYSCHDDKNEHTNNDLLNIDHDNNKNNITDELYSTYNVSVSHNKDPSNKENEIQN 3323 Query: 173 DVDNTTLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAK 215 + + D N ++ N ++E+++N + ++N + + K Sbjct: 3324 LISIDSSNENDENDENDENDENDENDENDENDENDENDENDEK 3366 Score = 30.9 bits (68), Expect = 9.2 Identities = 27/118 (22%), Positives = 53/118 (44%), Gaps = 15/118 (12%) Query: 104 THEDYLNVVYSSSEV ---- EKYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANR 159 T+ D LN+ + +++ E Y HN+D ++ +E QN S+D+S N Sbjct: 3280 TNNDLLNIDHDNNKNNITDELYSTYNVSVSHNKDPSNKENEI--QNLISIDSSNENDEND 3337 Query: 160 NAYVSLPQSEVNIDVDNTTLRFADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 +++ N + D D N ++ N +E+++N + ++N N +GT Sbjct: 3338 EN ---- DENDENDENDEN-----DENDENDENDENDEKDENDENDENDENFDNNNEGT 3386 WO 00/32825 PCT/IB99/02040 302 >gij5857951spIP21538|REB1_YEAST DNA-BINDING PROTEIN REB1 (QBP) >gil6261391pir||S45907 DNA-binding protein REB1 - yeast (Saccharomyces cerevisiae) >gil5362801emb|CAA84992| (Z35918) ORF YBRO49c [Saccharomyces cerevisiae] >gi|559944|embCAA863911 (Z46260) REB1 DNA-binding protein [Saccharomyces cerevisiae] Length = 810 Score = 45.7 bits (106), Expect = 3e-04 Identities = 34/158 (21%), Positives = 72/158 (45%), Gaps = 14/158 (8%) Query: 83 DREINRQTVEAFGMQVITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNEDTTSNTDETS 142 D+ N+++VE ++ + V ++++ +++ K+ + Q E + D N ++ S Sbjct: 7 DKNANQESVEEAVLKYVGVGLDHQNHDPQLHTKDLENKHSKKQNIVESSSDVDVNNNDDS 66 Query: 143 NQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTID--- NGKTVNKSSNE 199 N+N + D+S ++A L +E + +VD+ N +D N+ +E Sbj ct: 67 NRNEDNNDDSENISA ------- LNANESSSNVDHANSNEQHNAVMDWYLRQTAHNQQDDE 119 Query: 200 SNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKK 237 ++N N GN F++ ++ +D D KK Sbjct: 120 DDEN--NNNTDNGNDSNNHFSQSDIV--VDDDDDKNKK 153 >gil172372 (M58728) DNA-binding protein [Saccharomyces cerevisiae] Length = 809 Score = 45.7 bits (106), Expect = 3e-04 Identities = 34/158 (21%), Positives = 72/158 (45%), Gaps = 14/158 (8%) Query: 83 DREINRQTVEAFGMQVITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNEDTTSNTDETS 142 D+ N+++VE ++ + V ++++ +++ K+ + Q E + D N ++ S Sbj ct: 7 DKNANQESVEEAVLKYVGVGLDHQNHDPQLHTKDLENKHSKKQNIVESSNDVDVNNNDDS 66 Query: 143 NQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTID---NGKTVNKSSNE 199 N+N + D+S ++A L +E + +VD+ N +D N+ +E Sbjct: 67 NRNEDNNDDSENISA ------- LNANESSSNVDHANSNEQHNAVMDWYLRQTAHNQQDDE 119 Query: 200 SNQNAKRNQNQKGNAKGTQFTKQYLIDNIDKAYDLRKK 237 ++N N GN F++ ++ +D D KK Sbjct: 120 DDEN--NNNTDNGNDSNNHFSQSDIV--VDDDDDKNKK 153 >gil2952545 (AF051898) coronin binding protein [Dictyostelium discoideum] Length = 560 Score = 44.9 bits (104), Expect = 6e-04 Identities = 26/83 (31%), Positives = 39/83 (46%), Gaps = 5/83 (6%) Query: 131 NEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNG 190 N + +N +N N+ S +NS +N N+ + P N D DN T +NNT +N Sbjct: 404 NNNNNNNIINNNNSNSNSNNNSNN-NSNNNSNRNSPNHNNNGDNDNNT---- NNNTNNNN 458 Query: 191 KTVNKSSNESNQNAKRNQNQKGN 213 N ++N +N N N N N Sbjct: 459 NNNNNNNNNNNNNNNNNNNNNNN 481 Score = 41.4 bits (95), Expect = 0.006 Identities = 22/88 (25%), Positives = 43/88 (48%), Gaps = 6/88 (6%) Query: 130 HNEDTTSNTDETSNQNATSLDN--- STGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNT 186 + ++ +N++ SN N+ + N + G AN++ + P + +N + DN +NN Sbjct: 337 NRNNSNNNSNNNSNNNSNNSNNRNITNGSNANKS--- -NSPNNNLNTNNDNKNNNSNNNNN 393 Query: 187 IDNGKTVNKSSNESNQNAKRNQNQKGNA 214 +N S+N +N N N N N+ Sbjct: 394 SNNNSNNGNSNNNNNNNIINNNNSNSNS 421 Score = 40.6 bits (93), Expect = 0.011 Identities = 24/101 (23%), Positives = 41/101 (39%), Gaps = 2/101 (1%) Query: 115 SSEVEKYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDV 174 S+ L + ++N +N ++ N S +N+ N N S + N + WO 00/32825 PCT/IB99/02040 303 Sbjct: 370 SNSPNNNLNTNNDNKNNNSNNNNNSNNNSNNGNSNNNNNNNIINNNNSNSNSNNNSNNNS 429 Query: 175 DNTTLRFADN--NTIDNGKTVNKSSNESNQNAKRNQNQKGN 213 +N + R + N N DN N ++N +N N N N N Sbjct: 430 NNNSNRNSPNHNNNGDNDNNTNNNTNNNNNNNNNNNNNNNN 470 Score = 40.2 bits (92), Expect = 0.014 Identities = 21/80 (26%), Positives = 39/80 (48%), Gaps = 9/80 (11%) Query: 130 HNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDN 189 +N D +NT+ +N N + +N+ N N N + +N +ADN+ ++ Sbjct: 442 NNGDNDNNTNNNTNNNNNNNNNNNNNNN---------NNNNNNNNNNYADNSNNNS 492 Query: 190 GKTVNKSSNESNQNAKRNQN 209 + N +SN +N N +N+N Sbjct: 493 SNSNNNNSNSNNNNDNKNEN 512 Score = 39.5 bits (90), Expect = 0.024 Identities = 26/111 (23%), Positives = 44/111 (39%), Gaps = 20/111 (18%) Query: 112 VYSSSEVEKYLQSQ--GFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSE 169 VY + K+ ++ G +N ++ +N++ SN N ++N N N Sbj ct: 296 VYCTHHHTKFYETHRNGLLNNNNNSNNNSNSNSNNNNNGINNRNNSNNNSN --------- 346 Query: 170 VNIDVDNTTLRFADNNTIDNGKTVNKSS ------ NESNQNAKRNQNQKGNA 214 + N ++N I NG NKS+ N +N~N N N N+ Sbjct: 347 ---NNSNNNSNNSNNRNITNGSNANKSNSPNNNLNTNNDNKNNNSNNNNNS 394 Score = 37.5 bits (85), Expect = 0.094 Identities = 24/96 (25%), Positives = 41/96 (42%), Gaps = 1/96 (1%) Query: 124 SQGFTEHNEDTTSNTDETSNQNATSLDNSTGM-TANRNAYVSLPQSEVNIDVDNTTLRFA 182 S + +N + SN + ++ N DN+T T N N + + N + +N Sbjct: 421 SNNNSNNNSNNNSNRNSPNHNNNGDNDNNTN 480 Query: 183 DNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQ 218 +NN DN + +SN +N N+ N + K Q Sbjct: 481 NNNYADNSNNNSSNSNNNNSNSNNNNDNKNENSDNQ 516 Score = 35.6 bits (80), Expect = 0.36 Identities = 25/99 (25%), Positives = 42/99 (42%), Gaps = 18/99 (18%) Query: 130 HNEDTTSNTDETSNQNATSLDNST-GMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTID 188 +N + SN + +N N ++ N T G AN++ + P + +N + DN +NN + Sbjct: 339 NNSNNNSNNNSNNNSNNSNNRNITNGSNANKS--- NSPNNNLNTNNDNKNNNSNNNNNSN 395 Query: 189 NGKTV---------------NKSSNESNQNAKRNQNQKGN 213 N N S++ SN N+ N N N Sbjct: 396 NNSNNGNSNNNNNNNIINNNNSNSNSNNNSNNNSNNNSN 434 Score = 35.2 bits (79), Expect = 0.47 Identities = 21/94 (22%), Positives = 42/94 (44%), Gaps = 5/94 (5%) Query: 124 SQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFAD 183 + G + ++ +N T+N N + N+ N N+ + N + +N + + Sbjct: 362 TNGSNANKSNSPNNNLNTNNDNKNNNSNN-----NNNSNNNSNNGNSNNNNNNNIINNNN 416 Query: 184 NNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 +N+ N + N S+N SN+N+ + N N T Sbjct: 417 SNSNSNNNSNNNSNNNSNRNSPNHNNNGDNDNNT 450 Score = 35.2 bits (79), Expect = 0.47 Identities = 29/118 (24%), Positives = 53/118 (44%), Gaps = 12/118 (10%) Query: 115 SSEVEKYLQS-QGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNID 173 SS+ E ++ +GF + + T+N ++N D S+G + + + V+ P+S +N Sbjct: 114 SSDSEADIEDDKGFQD--KPITTNNSGSNNPLKNLKDYSSGSSGSSRSGVNQPRSNINNS 171 Query: 174 VDNTTLRFADNNT --------- IDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQ 222 D ++ +N+ I + T + NQN +NQNQ N Q +Q WO 00/32825 PCT/IB99/02040 304 Sbjct: 172 NDKYKSKSSSSNSNSSSSGGSLISSLLTGGNTYQNQNQNQNQNQNQNNNQSQLQQQQQ 229 Score = 34.4 bits (77), Expect = 0.81 Identities = 24/94 (25%), Positives = 38/94 (39%), Gaps = 12/94 (12%) Query: 131 NEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNG 190 N +T +N + +N N + +N+ N N S N N +NN+ N Sbjct: 451 TNNADNSNNNSSNSN------NNNSNSNN 504 Query: 191 KTVNKSSNESNQNAKR ------ NQNQKGNAKGTQ 218 NK+ N NQ+ R ++NQK + Q Sbjct: 505 NNDNKNENSDNQSVLRSNEKFTDENQKNGSDDQQ 538 Score = 33.6 bits (75), Expect = 1.4 Identities = 22/90 (24%), Positives = 35/90 (38%) Query: 124 SQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFAD 183 S N SN +++++ N N+ N N + + N + +N Sbj ct: 353 SNNSNNRNITNGSNANKSNSPNNNLNTNNDNKNNNSNNNNNSNNNSNNGNSNNNNNNNI I 412 Query: 184 NNTIDNGKTVNKSSNESNQNAKRNQNQKGN 213 NN N + N S+N SN N+ RN N Sbjct: 413 NNNNSNSNSNNNSNNNSNNNSNRNSPNHNN 442 >gi[535260embCAA829961 (Z30339) STARP antigen (Plasmodium reichenowi] Length = 655 Score = 44.5 bits (103), Expect = 7e-04 Identities = 31/114 (27%), Positives = 47/114 (41%), Gaps = 14/114 (12%) Query: 128 TEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVN------IDVDNTTLRF 181 T++N T TD + + +N+T A N + ++ N D +NT + Sbjct: 433 TDNNNTNTKATDSNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKA 492 Query: 182 ADNNTI-----DNGKTVNKSSNESNQNAKRNQNQKGNAKGT--- QFTKQYLIDN 227 DNN DN T K+++ +N N K N N K T T QY+ N Sbjct: 493 TDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNNTNQYVFAN 546 Score = 44.5 bits (103), Expect = 7e-04 Identities = 30/103 (29%), Positives = 44/103 (42%), Gaps = 13/103 (12%) Query: 128 TEHNEDTTSNTDETSNQNATSLDNS----TGMTANRNAYVSLPQSEVN----IDVDNTTL 179 T++N T TD+++N + + DN+ T T N N S D +NT Sbjct: 401 TDNNNTDTKATDKSNNTDTKATDNNNNTDTKATDNNNTNTKATDSNNTNTKATDNNNTNT 460 Query: 180 RFADNNTI-----DNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 + DNN DN T K+++ +N N K N N K T Sbjct: 461 KATDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKAT 503 Score = 42.6 bits (98), Expect = 0.003 Identities = 27/96 (28%), Positives = 43/96 (44%), Gaps = 10/96 (10%) Query: 128 TEHNEDTTSNTDETSNQNATSLD-NSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNT 186 T++N +T + + +N N + D N+T A N + ++ N NT + DNN Sbjct: 422 TDNNNNTDTKATDNNNTNTKATDSNNTNTKATDNNNTNTKATDNN---- NTNTKATDNNN 477 Query: 187 I-----DNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 DN T K+++ +N N K N N K T Sbjct: 478 TNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKAT 513 Score = 41.8 bits (96), Expect = 0.005 Identities = 35/150 (23%), Positives = 59/150 (39%), Gaps = 9/150 (6%) Query: 85 EINRQTVEAFGMQVITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNEDTTSNTDETSNQ 144 E N+ ++ G T+ + N + E + +Q T +N TT+ + N Sbjct: 118 ETNKTNIKLTGNNSTTINTNLTENTNA--TKKLTENVITNQILTGNNNTTTNTSSTEHNN 175 Query: 145 NATSLDNSTGMTANRNAYVSLPQSEVNIDVDNTTLRFADNNTIDNGKTVNKSSNESNQNA 204 N + NSTG T+ NI + N L +N T + T + ++ +N N+ WO 00/32825 PCT/I B99/02040 305 Sbj ct: 176 NINTNTNSTGNTSTTKKLTE ---- I -I TNQILTGNNNTTTNTSSTEHNNNINTNTNS 228 Query: 205 KRNQNQKGNAKGTQFTKQYLIDNIDKAYDL 234 N N N T + DNI+ +L Sbjct: 229 TDNSNTNTNLTDITTTTKKWTDNINTTQNL 258 Score = 41.8 bits (96), Expect = 0.005 Identities = 30/101 (29%), Positives = 43/101 (41%), Gaps = 13/101 (12%) Query: 130 HNEDTTSNTDETSNQNATSLDNS-TGMTANRNAYVSLPQSEVNIDV------DNTTLRFA 182 +N DT S ++ ++ AT DN+ T T N N + N D +NT + Sbjct: 363 NNTDTISTDNDNTDTKATDNDNTDTKATDNNNNTDTKATDNNNTDTKATDKSNNTDTKAT 422 Query: 183 DNN------TIDNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 DNN DN T K+++ +N N K N N K T Sbjct: 423 DNNNNTDTKATDNNNTNTKATDSNNTNTKATDNNNTNTKAT 463 Score = 40.6 bits (93), Expect = 0.011 Identities = 31/121 (25%), Positives = 47/121 (38%), Gaps = 31/121 (25%) Query: 128 TEHNEDTTSNTDETSNQNAT-----SLDNSTGMTANRNAYVSLPQSEVN------------ 171 TEHN + +NT+ T N + T ++ + +T N N + +E N Sbjct: 171 TEHNNNINTNTNSTGNTSTTKKLTENIITNQILTGNNNTTTNTSSTEHNNNINTNTNSTD 230 Query: 172 -------- IDVDNTTLRFADN -- T---- NTIDNGKTVNKSSNESNQNAKRNQNQKGNAKG 216 D+ TT ++ DN T N TV+ +N +N N K N N K Sbjct: 231 NSNTNTNLTDITTTTKKWTDNINTTQNLTTSTNTTTVSTDNNNNNINTKPTDNNNTNIKS 290 Query: 217 T 217 T Sbjct: 291 T 291 Score = 38.3 bits (87), Expect = 0.055 Identities = 28/98 (28%), Positives = 41/98 (41%), Gaps = 10/98 (10%) Query: 128 TEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVNIDVD-NTTLRFADNNT 186 TEHN + +NT+ S N+ + N T +T + + N+ NTT DNN Sbjct: 216 TEHNNNINTNTN--STDNSNTNTNLTDITTTTKKWTDNINTTQNLTTSTNTTTVSTDNNN 273 Query: 187 ------- -IDNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 DN T KS++ N K N+ + K T Sbjct: 274 NNINTKPTDNNNTNIKSTDNYNTGTKETDNKNTDIKAT 311 Score = 37.5 bits (85), Expect = 0.094 Identities = 31/106 (29%), Positives = 45/106 (42%), Gaps = 18/106 (16%) Query: 128 TEHNEDTTSNTDETSNQN----ATSLDNSTGMTANRNAYVSLPQSEVN-------IDVDN 176 T++N +T +T T N N AT N+T A N + ++ N D +N Sbjct: 390 TDNNNNT--DTKATDNNNTDTKATDKSNNTDTKATDNNNNTDTKATDNNNTNTKATDSNN 447 Query: 177 TTLRFADNN-----TIDNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 T + DNN DN T K+++ +N N K N N K T Sbjct: 448 TNTKATDNNNTNTKATDNNNTNTKATDWNNTNTKATDNNNTNTKAT 493 Score = 35.2 bits (79), Expect = 0.47 Identities = 24/109 (22%), Positives = 46/109 (42%), Gaps = 6/109 (5%) Query: 128 TEHNEDTTSNTDETSNQNATSLDNSTGMTANRNAYVSLPQSEVN~-----IDVDNTTLRF 181 T++N T TD + + +N+T A N + ++ N D +NT + Sbjct: 473 TDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKATDNNNTNTKA 532 Query: 182 ADNNTIDNGKTVNKSSNESNQNAKRNQNQKGNAKGTQFTKQYLIDNIDK 230 DNN N + +E+ + K N++ N++ + K + +DK Sbjct: 533 TDNNNNTNQYVFANNYDETTSDDKLNKDSCDNSEEKENIKSMINAYLDK 581 Score = 34.4 bits (77), Expect = 0.81 Identities = 26/126 (20%) , Positives = 46/126 (35%) , Gaps = 7/126 (5%) WO 00/32825 PCT/IB99/02040 306 Query: 99 ITVCITHEDYLNVVYSSSEVEKYLQSQGFTEHNEDTTSNTDETSNQNATSLDNSTGMTAN 158 IT T+ + ++ S + V S T +++ +N T N N ++ T Sbjct: 318 ITTDNTNTNVISTDNSKTNVISKDNSNTHTISTDNSKTNVISTDNNNTDTISTDNDNTDT 377 Query: 159 RNAYVSLPQSEVNIDVDNTTLRFADNNTID-------NGKTVNKSSNESNQNAKRNQNQK 211 + ++ + +NT + DNN D N + N +N + K N Sbjct: 378 KATDNDNTDTKATDNNNNTDTKATDNNNTDTKATDKSNNTDTKATDNNNNTDTKATDNNN 437 Query: 212 GNAKGT 217 N K T Sbjct: 438 TNTKAT 443 Score = 34.4 bits (77), Expect = 0.81 Identities = 30/100 (30%), Positives = 44/100 (44%), Gaps = 14/100 (14%) Query: 131 NEDTTSNTDETSNQNATSLDNS-TGMTANRNAY---VSLPQSEVNI---DVDNTTLRFAD 183 N + T TD T N N S DNS T + + N+ +S S+ N+ D +NT D Sbjct: 313 NNNITITTDNT-NTNVISTDNSKTNVISKDNSNTHTISTDNSKTNVISTDNNNTDTISTD 371 Query: 184 NNTIDNGKTVNKSS------NESNQNAKRNQNQKGNAKGT 217 N+ D T N ++ N +N + K N + K T Sbjct: 372 NDNTDTKATDNDNTDTKATDNNNNTDTKATDNNNTDTKAT 411 Score = 34.4 bits (77), Expect = 0.81 Identities = 28/101 (27%), Positives = 41/101 (39%), Gaps = 15/101 (14%) Query: 131 NEDTTSNTDETSNQNATSLDNSTGMTA--NRNAYVSLPQSEVNIDV------DNTTLRFA 182 N DT + ++ ++ AT +N+T A N N N D +NT + Sbj ct: 374 NTDTKATDNDNTDTKATDNNNNTDTKATDNNNTDTKATDKSNNTDTKATDNNNNTDTKAT 433 Query: 183 DNNTIDNGK------TVNKSSNESNQNAKRNQNQKGNAKGT 217 DNN N K T K+++ +N N K N N K T Sbjct: 434 DNNN-TNTKATDSNNTNTKATDNNNTNTKATDNNNTNTKAT 473 Score = 32.5 bits (72), Expect = 3.1 Identities = 30/110 (27%), Positives = 40/110 (36%), Gaps = 23/110 (20%) Query: 131 NEDTTSNTDETSNQNATSLDNS-----TGMTANRNAYVSLPQS ---- EVNIDVDNTTLRF 181 N +TT N ++N S DN+ T T N N + + D NT ++ Sbjct: 251 NINTTQNLTTSTNTTTVSTDNNNNNINTKPTDNNNTNIKSTDNYNTGTKETDNKNTDIKA 310 Query: 182 ADNNTI -------------- -DNGKTVNKSSNESNQNAKRNQNQKGNAKGT 217 DNN I DN KT S + SN + N K N T Sbjct: 311 TDNNNITITTDNTNTNVISTDNSKTNVISKDNSNTHTISTDNSKTNVIST 360 >gil1429240|emb|CAA67659| (X99260) lower collar protein (Bacteriophage B103] Length = 293 Score = 43.8 bits (101), Expect = 0.001 Identities = 53/204 (25%), Positives = 79/204 (37%), Gaps = 42/204 (20%) Query: 56 EKVFKG----FSLKDELSDLLFKKSFTIHFLD----REINRQTVEAFGMQVITVCITHED 107 EK+ KG F + + D ++K F HF+ REI +T F + T I + Sbjct: 26 EKIEKGRPKLFDFQYPIFDESYRKVFETHFIRNFYMREIGFETEGLFKFNLETWLIINMP 85 Query: 108 YLNVVYSSSEVEKY-------LQSQGFTEH------NEDTT--------SNTDETSNQNA 146 Y N ++ S E+ KY L + G ++ N DTT SNT + NA Sbjct: 86 YFNKLFES-ELIKYDPLENTRLNTTGNKKNDTERNDNRDTTGSMKADGKSNTKTSDKTNA 144 Query: 147 TSLDNSTGMTA--------NRNAYVSLPQSEVNIDVDN--TTLRFADNNTIDNGKTVNKS 196 T G T NR P S +N+ ++ TL +A + I+ T NK Sbjct: 145 TGSSKEDGKTTGSVTDDNFNRKIDSDQPDSRLNLTTNDGQGTLEYA--SAIEENNTNNKR 202 Query: 197 SNESNQNAKRNQNQKGNAKGTQFT 220 + N + + GT T Sbjct: 203 NTTGTNNVTSSAESESTGSGTSDT 226 Query= pt|110879 44AHJDORFOO9 Phage 44AHJD ORF 15744-649612 1 (250 letters) WO 00/32825 PCT/IB99/02040 307 >gil27649811emb|CAA69021.11 (Y07739) N-acetylmuramoyl-L-alanine amidase (Staphylococcus phage Twort] Length = 467 Score = 180 bits (452), Expect = le-44 Identities = 89/157 (56%), Positives = 109/157 (68%), Gaps = 8/157 (5%) Query: 1 MKSQQQAKEWIYKHEGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMGNAKDAINNDFK 60 MK+ +QA+ +I G DFDG YG+QCMDL+V Y+Y++TDGK+RMWGNAKDAINN F Sbjct: 1 MKTLKQAESYIKSKVNTGTDFDGLYGYQCMDLAVDYIYHVTDGKIRMWGNAKDAINNSFG 60 Query: 61 GLATVYKNTPSFKPQLGDVAVYTNGQ--- YGHIQCVLS ---- GNLDYYTCLEQNWLGGGF 113 G ATVYKN P+F+P+ GDV V+T G YGHI V + G+L Y T LEQNW G G Sbjct: 61 GTATVYKNYPAFRPKYGDVVVWTTGNFATYGHIAIVTNPDPYGDLQYVTVLEQNWNGNGI 120 Query: 114 DGWEKATIRTHYYDGVTHFIRPKFSGSNS-KALETSK 149 E ATIRTH Y G+THFIRP F+ +S K +T K Sbjct: 121 YKTELATIRTHDYTGITHFIRPNFATESSVKKKDTKK 157 Score = 61.7 bits (147), Expect = 6e-09 Identities = 41/125 (32%), Positives = 57/125 (44%), Gaps = 8/125 (6%) Query: 125 YYDGVTHFIRPKFSGSNSKALETSKVNTFGKWKRNQYGTYYRNENGTFTC-GFLPIFARV 183 YY+G T P +K + +T G W N YGTYY++E+ TF C I R Sbjct: 346 YYEGKTPV--PTVVNQKAKTKPVKQSSTSG-WNVNNYGTYYKSESATFKCTARQGIVTRY 402 Query: 184 GSPKLSEPNGYWFQPNGYTPYNEVCLSDGYVWIGYNWQGTR-YYLPVRQWNGKTGNSYSV 242 P + P Y+ VC DGYVWI + G + ++PVR W+ N+ + Sbjct: 403 TGPFTTCPQAGVLYYGQSVTYDTVCKQDGYVWISWTTNGGQDVWMPVRTWD---KNTDIM 459 Query: 243 GIPWG 247 G WG Sbjct: 460 GQLWG 464 >gi1113675sp| P24556|ALYS_STAAU AUTOLYSIN (N-ACETYLMURAMOYL-L-ALANINE AMIDASE) >gi|79887|pir||JQ1147 N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28) - Staphylococcus aureus >gil153067 (M76714) peptidoglycan hydrolase [Staphylococcus aureus] Length = 481 Score = 118 bits (292), Expect = 6e-26 Identities = 56/117 (47%), Positives = 68/117 (57%), Gaps = 1/117 (0%) Query: 135 PKFSGSNSKALETSKVNTFGK-WKRNQYGTYYRNENGTFTCGFLPIFARVGSPKLSEPNG 193 P + SN + ++ V WKRN+YGTYY E+ FT G PI R P LS P G Sbjct: 365 PVATVSNESSASSNTVKPVASAWKRNKYGTYYMEESARFTNGNQPITVRKVGPFLSCPVG 424 Query: 194 YWFQPNGYTPYNEVCLSDGYVWIGYNWQGTRYYLPVRQWNGKTGNSYSVGIPWGVFS 250 Y FQP GY Y EV L DG+VW+GY W+G RYYLP+R WNG + +G WG S Sbjct: 425 YQFQPGGYCDYTEVMLQDGHVWVGYTWEGQRYYLPIRTWNGSAPPNQILGDLWGEIS 481 Score = 78.0 bits (189), Expect = 7e-14 Identities = 48/109 (44%), Positives = 62/109 (56%), Gaps = 6/109 (5%) Query: 15 EGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMWGNAKDA-INNDFKGLATVYKNTPSFK 73 EG + D YGFQC D + A + + G + AKD N+F GLATVY+NTP F Sbjct: 18 EGKQFNVDLWYGFQCFDYANAG-WKVLFGLLLKGLGAKDIPFANNFDGLATVYQNTPDFL 76 Query: 74 PQLGDVAVYTNGQ--- YGHIQCVLSGNLDYYTCLEQNWLGGGF-DGWEK 118 Q GD+ V+ + YGH+ V+ LDY EQNWLGGG+ DG E+ Sbjct: 77 AQPGDMVVFGSNYGAGYGHVAWVIEATLDYIIVYEQNWLGGGWTDGIEQ 125 >gif1763243 (U72397) amidase [bacteriophage 80 alpha) Length = 481 Score = 118 bits (292), Expect = 6e-26 Identities = 56/117 (47%), Positives = 68/117 (57%), Gaps = 1/117 (0%) Query: 135 PKFSGSNSKALETSKVNTFGK-WKRNQYGTYYRNENGTFTCGFLPIFARVGSPKLSEPNG 193 P + SN + ++ V WKRN+YGTYY E+ FT G PI R P LS P G Sbjct: 365 PVATVSNESSASSNTVKPVASAWKRNKYGTYYMEESARFTNGNQPITVRKVGPFLSCPVG 424 WO 00/32825 PCT/IB99/02040 308 Query: 194 YWFQPNGYTPYNEVCLSDGYVWIGYNWQGTRYYLPVRQWNGKTGNSYSVGIPWGVFS 250 Y FQP GY Y EV L DG+VW+GY W+G RYYLP+R WNG + +G WG S Sbjct: 425 YQFQPGGYCDYTEVMLQDGHVWVGYTWEGQRYYLPIRTWNGSAPPNQILGDLWGEIS 481 Score = 83.5 bits (203), Expect = 2e-15 Identities = 50/115 (43%), Positives = 65/115 (56%), Gaps = 6/115 (5%) Query: 9 EWIYKHEGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMWGNAKDA-INNDFKGLATVYK 67 EW+ EG + D YGFQC D + A + + G + AKD N+F GLATVY+ Sbj ct: 12 EWLKTSEGKQFNVDLWYGFQCFDYANAG-WKVLFGLLLKGLGAKDIPFANNFDGLATVYQ 70 Query: 68 NTPSFKPQLGDVAVYTNGQ--- YGHIQCVLSGNLDYYTCLEQNWLGGGF-DGWEK 118 NTP F Q GD+ V+ + YGH+ V+ LDY EQNWLGGG+ DG E+ Sbj ct: 71 NTPDFLAQPGDMVVFGSNYGAGYGHVAWVIEATLDYIIVYEQNWLGGGWTDGIEQ 125 >gil4574237|gb|AAD23962.1|AF106851_1 (AF106851) LytN [Staphylococcus aureus] Length = 383 Score = 84.3 bits (205), Expect = 9e-16 Identities = 48/128 (37%), Positives = 68/128 (52%), Gaps = 7/128 (5%) Query: 15 EGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMWGNAKDAINNDFKGLATVYKNTPSFKP 74 E G DFDG+YG+QC DL Y ++ ++ +G N+F A +Y NTP+FK Sbjct: 252 ENRGWDFDGSYGWQCFDLVNVYWNHLYGHGLKGYGAKDIPYANNFNSEAKIYHNTPTFKA 311 Query: 75 QLGDVAVYT -- NGQYGHIQCVLSGNLD---- YYTCLEQNWLGGGFDGWEKATIRTHYYD 127 + GD+ V++ G YGH VL+G+ D + L+QNW GG+ E A H Y+ Sbjct: 312 EPGDLVVFSGRFGGGYGHTAIVLNGDYDGKLMKFQSLDQNWNNGGWRKAEVAHKVVHNYE 371 Query: 128 GVTHFIRP 135 FIRP Sbjct: 372 NDMIFIRP 379 >gij3767593|dbjjBAA33856.1| (AB015195) LytN {Staphylococcus aureus] Length = 383 Score = 84.3 bits (205), Expect = 9e-16 Identities = 48/128 (37%), Positives = 68/128 (52%), Gaps = 7/128 (5%) Query: 15 EGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMWGNAKDAINNDFKGLATVYKNTPSFKP 74 E G DFDG+YG+QC DL Y ++ ++ +G N+F A +Y NTP+FK Sbjct: 252 ENRGWDFDGSYGWQCFDLVNVYWNHLYGHGLKGYGAKDIPYANNFNSEAKIYHNTPTFKA 311 Query: 75 QLGDVAVYT ---NGQYGHIQCVLSGNLD---- YYTCLEQNWLGGGFDGWEKATIRTHYYD 127 + GD+ V++ G YGH VL+G+ D + L+QNW GG+ E A H Y+ Sbjct: 312 EPGDLVVFSGRFGGGYGHTAIVLNGDYDGLMKFQSLDQNWNNGGWRKAEVAHKVVHNYE 371 Query: 128 GVTHFIRP 135 FIRP Sbjct: 372 NDMIFIRP 379 >gil2764983|emb1CAA69022.1| (Y07740) cell wall hydrolase Ply187 [Staphylococcus phage 187] Length = 628 Score = 76.9 bits (186), Expect = 2e-13 Identities = 50/144 (34%), Positives = 68/144 (46%), Gaps = 18/144 (12%) Query: 5 QQAKEWIYKHEGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMW-----GNAKDAINNDF 59 +Q +W G+GVD DG YG QC DL Y++ R W GNA+D + Sbjct: 12 KQVVDWAINLIGSGVDVDGYYGRQCWDLP-NYIFN------RYWNFKTPGNARDMAWYRY 64 Query: 60 KGLATVYKNTPSFKPQLGDVAVYTNGQY-----GHIQCVLS-GNLDYYTCLEQNWLGGGF 113 V++NT F P+ GD+AV+T G Y GH V+ Y+ ++QNW Sbjct: 65 PEGFKVFRNTSDFVPKPGDIAVWTGGNYNWNTWGHTGIVVGPSTKSYFYSVDQNWNNSNS 124 Query: 114 DGWEKATIRTHYYDGVTHFIRPKF 137 A H Y GVTHF+RP + Sbjct: 125 YVGSPAAKIKHSYFGVTHFVRPAY 148 WO 00/32825 PCT/IB99/02040 309 >gil32877321splO05156|ALE1_STACP GLYCYL-GLYCINE ENDOPEPTIDASE ALE-1 PRECURSOR >gif1890068|dbjjBAA13069j (D86328) ALE-1 (Staphylococcus capitis] Length = 362 Score = 73.4 bits (177), Expect = 2e-12 Identities = 47/117 (40%), Positives = 61/117 (51%), Gaps = 10/117 (8%) Query: 132 FIRPKFSGSNSKALETSKVNTFGKWKRNQYGTYYRNENGTFTCGFLPIFARVGSPKLSEP 191 F++ GSNS TS N G +K N+YGT Y++E+ +FT I R+ P S P Sbjct: 252 FLKSAGYGSNS ---- TSSSNNNG-YKTNKYGTLYKSESASFTAN-TDIITRLTGPFRSMP 305 Query: 192 NGYWFQPNGYTPYNEVCLSDGYVWIGYNW-QGTRYYLPVRQWNGKTGNSYSVGIPWG 247 + Y+EV DG+VW+GYN G R YLPVR WN TG +G WG Sbjct: 306 QSGVLRKGLTIKYDEVMKQDGHVWVGYNTNSGKRVYLPVRTWNESTG---ELGPLWG 359 >gi1799261pir||A25881 lysostaphin precursor - Staphylococcus simulans >giJ153047 (M15686) lysostaphin (ttg start codon) [Staphylococcus simulans) Length = 389 Score = 69.5 bits (167), Expect = 3e-11 Identities = 48/133 (36%), Positives = 62/133 (46%), Gaps = 20/133 (15%) Query: 131 HFIRPKFSGSNSKALETS---KVNTFGK------------WKRNQYGTYYRNENGTFTCG 175 HF R S SNS A + K +GK WK N+YGT Y++E+ +FT Sbjct: 258 HFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNTGWKTNKYGTLYKSESASFTPN 317 Query: 176 FLPIFARVGSPKLSEPNGYWFQPNGYTPYNEVCLSDGYVWIGYNW-QGTRYYLPVRQWNG 234 I R P S P + Y+EV DG+VW+GY G R YLPVR WN Sbjct: 318 -TDIITRTTGPFRSMPQSGVLKAGQTIHYDEVMKQDGHVWVGYTGNSGQRIYLPVRTWNK 376 Query: 235 KTGNSYSVGIPWG 247 T ++G+ WG Sbjct: 377 STN---TLGVLWG 386 >gil1264961sp|P10548|LSTPSTAST LYSOSTAPHIN PRECURSOR (GLYCYL-GLYCINE ENDOPEPTIDASE) >gi|799271pir S01079 lysostaphin precursor - Staphylococcus simulans bv. staphylolyticus >gil581744|emb|CAA294941 (X06121) lysostaphin (AA 1-480) (Staphylococcus simulans bv. staphylolyticus] Length = 480 Score = 69.5 bits (167), Expect = 3e-11 Identities = 48/133 (36%), Positives = 62/133 (46%), Gaps = 20/133 (15%) Query: 131 HFIRPKFSGSNSKALETS---KVNTFGK------------WKRNQYGTYYRNENGTFTCG 175 HF R S SNS A + K +GK WK N+YGT Y++E+ +FT Sbjct: 349 HFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNTGWKTNKYGTLYKSESASFTPN 408 Query: 176 FLPIFARVGSPKLSEPNGYWFQPNGYTPYNEVCLSDGYVWIGYNW-QGTRYYLPVRQWNG 234 I R P S P + Y+EV DG+VW+GY G R YLPVR WN Sbjct: 409 -TDIITRTTGPFRSMPQSGVLKAGQTIHYDEVMKQDGHVWVGYTGNSGQRIYLPVRTWNK 467 Query: 235 KTGNSYSVGIPWG 247 T ++G+ WG Sbjct: 468 STN---TLGVLWG 477 >gi|3287967|spIP10547|LSTP_STASI LYSOSTAPHIN PRECURSOR (GLYCYL-GLYCINE ENDOPEPTIDASE) >gil2072411 (U66883) lysostaphin (Staphylococcus simulans] Length = 493 Score = 69.5 bits (167), Expect = 3e-11 Identities = 48/133 (36%), Positives = 62/133 (46%), Gaps = 20/133 (15%) Query: 131 HFIRPKFSGSNSKALETS---KVNTFGK------------WKRNQYGTYYRNENGTFTCG 175 HF R S SNS A + K +GK WK N+YGT Y++E+ +FT Sbjct: 362 HFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNTGWKTNKYGTLYKSESASFTPN 421 Query: 176 FLPIFARVGSPKLSEPNGYWFQPNGYTPYNEVCLSDGYVWIGYNW-QGTRYYLPVRQWNG 234 WO 00/32825 PCT/IB99/02040 310 I R P S P + Y+EV DG+VW+GY G R YLPVR WN Sbjct: 422 -TDIITRTTGPFRSMPQSGVLKAGQTIHYDEVMKQDGHVWVGYTGNSGQRIYLPVRTWNK 480 Query: 235 KTGNSYSVGIPWG 247 T ++G+ WG Sbjct: 481 STN---TLGVLWG 490 >gil3341932|dbj|BAA31898.1| (AB009866) amidase (peptidoglycan hydrolase) [bacteriophage phi PVL] Length = 484 Score = 68.3 bits (164), Expect = 6e-11 Identities = 52/150 (34%), Positives = 71/150 (46%), Gaps = 17/150 (11%) Query: 3 SQQQAKEWIYKHEGAGVDFDGAYGFQCMDLSVAYVYYITDGKVRMWGNAKDAINNDFKGL 62 ++ QA++W G + D YGFQC D + + + I G+ R+ G I D K Sbjct: 4 TKNQAEKWFDNSLGKQFNPDLFYGFQCYDYASMF-FMIATGE-RLQGLYAYNIPFDNKAR 61 Query: 63 ATVY----KNTPSFKPQLGDVAVYTN---GQYGHIQCVLSGNLDYYTCLEQNWLGGGF-- 113 Y KN SF PQ D+ V+ + G GH++ V S NL+ +T QNW G G+ Sbj ct: 62 IEKYGQIIKNYDSFLPQKLDIVVFPSKYGGGAGHVEIVESANLNTFTSFGQNWNGKGWTN 121 Query: 114 ---- DGW--EKATIRTHYYDGVTHFIRPKF 137 GW E T HYYD +FIR F Sbjct: 122 GVAQPGWGPETVTRHVHYYDDPMYFIRLNF 151 Query= pt|110882 44AHJDORF012 Phage 44AHJD ORF 18391-881313 1 (140 letters) >gil1405281spIP248111YQXHBACSU HYPOTHETICAL 15.7 KD PROTEIN IN SPOIIIC-CWLA INTERGENIC REGION (ORF2) >gil322189|pirI|B44816 orf2 5'of autolytic amidase Bacillus subtilis >gi|142801 (M59232) open reading frame 2 [Bacillus subtilis] >gijl2l7874|dbjjBAA06959| (D32216) ORF121 [Bacillus subtilis] >gi|1303767|dbjlBAA124231 (D84432) YqdD (Bacillus subtilis] >gil2635036|emb|CAB145321 (Z99117) alternate gene name: yqdD; similar to holin [Bacillus subtilis} Length = 140 Score = 80.4 bits (195), Expect = 6e-15 Identities = 45/130 (34%), Positives = 67/130 (50%), Gaps = 3/130 (2%) Query: 4 VKFRFTDSEAFHMFIYAGDLKLLYFLFVLMFVDIITGISKAIKNNNLWSKKSMRGFSKKX 63 + F D ++F G +K L L VL +D++TG+ KA K L S+ + G+ +K Sbjct: 8 INFETLDLARVYLF--- GGVKYLDLLLVLSIIDVLTGVIKAWKFKKLRSRSAWFGYVRKL 64 Query: 64 XXXXXXXXXXXXXXXXXXKGGLLMITIFYYIANEGLSIVENCAEMDVLVPEQIKDKLRVI 123 G L T+ +YIANEGLSI EN A++ V +P I D+L+ I Sbjct: 65 LNFFAVILANVIDTVLNLNGVLTFGTVLFYIANEGLSITENLAQIGVKIPSSITDRLQTI 124 Query: 124 KNDTEKSDNN 133 +N+ E+S NN Sbjct: 125 ENEKEQSKNN 134 >giI412663ldbj|BAA36651.1| (AB016282) ORF45 (bacteriophage phi-105] Length = 135 Score = 76.1 bits (184), Expect = le-13 Identities = 44/115 (38%), Positives = 61/115 (52%), Gaps = 4/115 (3%) Query: 21 GDLKLLYFLFVLMFVDIITGISKAIKNNNLWSKKSMRGFSKKXXXXXXXXXXXXXXXXXX 80 G++K L + VL +DIITG+ KA K L S+ + G+ +K Sbjct: 17 GEVKYLDLMLVLNIIDIITGVIKAWKFKELRSRSAWFGYVRKMLSFLVVIVANAIDTIMD 76 Query: 81 XKGGLLMITIFYYIANEGLSIVENCAEMDVLVPEQIKDKLRVIKND----TEKSD 131 G L T+ +YIANEGLSI EN A++ V +P I D+L VI++D TEK D - - Sbjct: 77 LNGVLTFATVLFYIANEGLSITENLAQIGVKIPAVITDRLHVIESDNDQKTEKDD 131 >gil141088|spIP26835|YNGD_CLOPE HYPOTHETICAL 14.9 KD PROTEIN IN NAGH 3REGION (ORFD) >gil10759671pirl IS43905 hypothetical protein D - Clostridium perfringens >gil455154 (M81878) WO 00/32825 PCT/IB99/02040 311 ORF D [Clostridium perfringens] Length = 132 Score = 60.9 bits (145), Expect = 4e-09 Identities = 38/127 (29%), Positives = 63/127 (48%), Gaps = 3/127 (2%) Query: 1 MNEVKFRFTDSEAFHMFIY-AGDLKLLYFLFVLMFVDIITGISKAIKNNNLWSKKSMRGF 59 +N +K+ +I+ A D+ L+ L V +F+D +TG+ K K+ L S +RG Sbjct: 5 INYIKWGIVSLGTLFTWIFGAWDIPLITLL-VFIFLDYLTGVIKGCKSKELCSNIGLRGI 63 Query: 60 SKKXXXXXXXXXXXXXXXXXXXKGGLLMITI-FYYIANEGLSIVENCAEMDVLVPEQIKD 118 +KK + I ++YI NEG+SI+ENCA + V +PE++K Sbjct: 64 TKKGLILVVLLVAVMLDRLLDNGTWMFRTLIAYFYIMNEGISILENCAALGVPIPEKLKQ 123 Query: 119 KLRVIKN 125 L+ + N Sbjct: 124 ALKQLNN 130 >gij2293160 (AF008220) YtkC [Bacillus subtilis] >gil2635548|embiCAB15042| (Z99119) similar to autolytic amidase (Bacillus subtilis] Length = 134 Score = 36.4 bits (82), Expect = 0.099 Identities = 25/109 (22%), Positives = 41/109 (36%) Query: 17 FIYAGDLKLLYFLFVLMFVDIITGISKAIKNNLWSKKSMRGFSKKXXXXXXXXXXXXXX 76 F + G L LM ++ I+ K + L KK KK Sbjct: 20 FFFGGFQYSFLILLSLMAIEFISTTLKETIIHKLSFKKVFARLVKKLVTLALISVCHFFD 79 Query: 77 XXXXXKGGLLMITIFYYIANEGLSIVENCAEMDVLVPEQIKDKLRVIKN 125 +G + + I +YI E + IV + ++ VP+ + D L +KN Sbjct: 80 QLLNTQGSIRDLAIMFYILYESVQIVVTASSLGIPVPQMLVDLLETLKN 128 >gil11819731emb|CAA87743.11 (Z47794) holin protein [Bacteriophage CP-1] Length = 134 Score = 31.3 bits (69), Expect = 3.3 Identities = 27/88 (30%), Positives = 36/88 (40%), Gaps = 5/88 (5%) Query: 29 LFVLMFVDIITGISKAIKNNNLWSKKSMRGFSKKXXXYXXXXXXXXXXXXK--GGLL 86 LF L+ D ITG KA K S ++G K G +L Sbjct: 18 LFALILFDFITGFLKAWKWKVTDSWTGLKGVIKHTLTFIFYYFVAVFLTYIHAMAVGQIL 77 Query: 87 MITIFYYIANEGLSIVENCAEMDVLVPE 114 ++ I Y A LSI+EN A M V +P+ Sbjct: 78 LVIINLYYA---LSIMENLAVMGVFIPK 102 WO 00/32825 PCT/IB99/02040 312 Table 21 Phage 182 complete genome sequence. 17833 nucleotides. 1 tagaatattg tcataaaaca caaacataat aatgcatatt attgtttaca aatatgtaat ttcgtgatat 71 aatatatttg taagttaaag gaggtgacaa aagaacaaat cataaatgct ttagaaatig caaaaactat 141 tggaggaaaa ataatgaaat attcactaca acaaatagat gaaattaaat caacaatttt cagaattaga 211 ttaaaaaggc atgaactaga ggaattggtg gacgaagtaa acgatattgc taaagatccg gaggaaagat 281 atcttttatc gttttattac acagaagaag aacgtttgtt tgaaattccc tctgcaagat taatagatta 351 ttacaacgaa aagatcacaa atctgaaatc ggaaatcata tcactcgaaa aaagattaca aaaactagta 421 aaataattac acaaaaagct ttacaaatat aacacatcat gttatactaa aagagtagta agggaacgga 491 aaatacctta cttcacacct caatcattct tatcaaaata caaaaggagg gaaaataatg ggtcgaaaac 561 taatgcaacg aaacgtaaca tcaactaaag tagaattctc agaagttatc gtacaagatg gagcgccaac 631 aattgtacca tgcgaaccag ttgtcttaac aggaaaactt tcagaagaaa aagctttatc agcgatcaaa 701 cgtaaaaacc ctgataaaaa cgtagttgta acaaatgttt cacatgaaac agcgctttac acaatgccag 771 tcgataaatt tatcgagtta gcagacaaat caacacaagc ctaataaaaa caaaactaaa acaaaacaga 841 ggagattata atcatggaaa tcgtaaaaag cacatttgac acacaaacac cagaaggaat gttacaagta 911 ttcaatgcca caaacggggc ttcaattccg ttacgtaacg caattggcga agtactagaa ttgaaagata 981 ttctagttta ctcagacgaa gtttctggtt ttggtggagc cgaaccatca caagcagaac tagtcgcttt 1051 cttcacagaa gatggtaaaa cttatgcggg tgtatcagca gtagcaacaa aatcagctaa aaacctaatt 1121 gatatgatga ctgctaaccc tgacatcaaa ccaaaaattt cttttgtcga aggaaaatca aacggtggac 1191 aaaaatttgt aaatctacaa gtggtttcac tgtagcataa aaatacagga atctagtaag ccacttagcg 1261 aatctcgcta ggtggttttt attatgtttc tacattgagg tgtgtagaat tgaccgtaag aatatcaaag 1331 aatgatagag ccaagttaga gaaaatctac ggtaaatcta acaaagctcg taaaaaatac aatcgtttaa 1401 gacaaaaagg agttgaggaa aggcaacttc caactgttcc aacatcaaag aaaagactta ttgactacgt 1471 aaaatcaaca aatatgagtc gtagtgattt taacaagatg ttagacgagt tggtagattt tgcacaacct 1541 tacaacgaga attacatttt tgagatcaac aagcgaaat ttgcaatctc aagagcgcaa atcaaagaag 1611 cgcaaattaa aacagagcaa gctcaaaaag cgaaagaaga acactacaaa gagcttaaca aagttgaagt 1681 taagaagccc acagaaaaca caattgtcac accaactatt ttaacagagt taggtgctga cttacctttt 1751 caagcaatac cagattttaa tattgacgct ttcacttctc cagaaggagt tcagtcttat ttagaaaata 1821 taggaaaaca agacgaacaa tattttgacg aaagagacca actttattac gacaatttca gacaagcgat 1891 gtttactatt ttcaattcag acgctgacga tattgttcgt ttacttgact caatggggct tgatctattt 1961 atgaaaacat atgttagtaa cttcttagac atgaaccttg actacattta tgacgaagca gaagtacaac 2031 agaaaaaaga acaagtttac agtaagattg caaaagtgat cgagtctgaa acaggtggag aagtcccctc 2101 atataacccc acgaagaaca tcacaattaa ttcagaaaca ggagaagaat tatgattaag aaatatactg 2171 gcgactttga aacaacaact gatctcaacg attgtcgtgt atggtcgtgg ggcgtatgcg atatagacaa 2241 cgttgacaat atgacgttcg gtttagaaat cgattctttt tttgagtggt gtaaaatgca aggcagcaca 2311 gacatttatt tccacaacga aaaatttgac ggagagttta tgctttcatg gttattcaaa aatggtttca 2381 aatggtgtaa agaagcaaaa gaagatcgaa cattctccac actcatatca aatatgggtc aatggtatgc 2451 tttggaaatt tgttgggaag ttaattacac aacaacaaaa tcaggtaaaa cgaaaaaaga gaaatctcga 2521 acaataattt atgatagcct taaaaaatat ccttttccag tgaaacaaat tgcagaagct tttaattttc 2591 ctataaaaaa aggcgaaata gattatacaa aagaaagacc tattggttac aaaccaacaa aagatgaatg 2661 ggagtattta aagaacgaca ttcagattat ggcgatggca ttaaaaattc aattcgatca aggactaact 2731 cgaatgacta gaggaagcga cgctttaggc gattacaaag attggctaaa agctacacat ggaaaatcaa 2801 ctttcaaaca atggtttcct attttgtctt tagggtttga taaagactta cgtaaagcat acaaaggcgg 2871 cttcacttgg gtaaacaaag tttttcaagg gaaagaaata ggtgacggca ttgtctttga tgtcaactct 2941 ttgtatccct ctcaaatgta cgtaagacct ttaccatatg gaacacctct attctacgaa ggagaataca 3011 aaccgaacaa cgactatccg ctgtacattc aaaatatcaa agtaagattc cgtttaaagg agggttatat 3081 tccaaccatt caagttaagc aaagttcatt attcattcaa aacgaatatc ttgaatcaag tgtaaacaag 3151 ttaggagttg acgaattaat cgatcttact cttacaaatg ttgacctaga attatttttt gaacactacg 3221 atattttaga gatacattac acttacggat atatgttcaa agcttcttgt gatatgttca aaggctggat 3291 cgataaatgg atcgaagtaa agaacaccac cgaaggggct agaaaagcta acgccaaagg tatgttaaat 3361 agcttgtatg gaaagttcgg aacaaaccct gacattacag gaaaagtgcc ttacatgggc gaggacggca 3431 ttgttcgatt gacactagga gaagaagaat taagagatcc tgtttatgtt ccgcttgcta gttttgtgac 3501 ggcttggggt agatatacta ccattacaac cgctcaaaaa tgttttgatc gcattattta ttgtgataca 3571 gatagcattc atctagtagg aacagaagtt ccagaagcaa tcgatcactt ggttgatcct aaaaaacttg 3641 gttattgggg gcatgaaagc acatttcaac gagcaaaatt cattcggcag aaaacatacg tagaagaaat 3711 tgatggcgaa ttaaatgtaa agtgtgctgg tatgccagat cgaataaaag agattgtaac ttttgacaat 3781 tttgaagttg gtttttcaag ctatggaaag ttgctaccta aaagaacaca aggtggcgtg gtattagtag 3851 acacaatgtt tacaatcaaa taaggaggac taataatgga actatataaa gcaatgttta tcgtacgtga 3921 tgaaggtact attgacggtt acgatactga acactatgta gatatttctt tacatgactt tgaagaaata 3991 tatggaaaag aaacacgtga aattgaagca gtaacattag taaaaacagg aaatttaaaa aaataaatta 4061 tttacatcct ttgcaaagta tggtaaaata ttcttgtgat agttgacaag agtcaaattt ggcgagattg 4131 ggcgaatgta cacgtgaaat atcgtgcgct cccgttaagt tatggacaca taaacgtttt gaccgtcaac 4201 caatcgcaaa aaccttttag gagtagccct taaatgtggc tactcttttt tgtgtttcac aggattatgt 4271 ttcacgtgaa acagttttta tggtataata gaatcaaaag gaggtggaga ttatggaaat taaagaacmc 4341 gaatcaattt taaatggtat tcttgaaagt gtcacagacg gtgaagcaag atcaaagatt gtagaicatc 4411 ttgaagcatt gcgagaagac tacggagcaa caactgaagc tttgacatca gcaaatagca cacttgaaaa 4481 gttaaagaaa gataacgaag cgttggttat ttcaaactca aaattgttcc gagaacgagc gatcgtagaa 4551 ccagcagaaa ataacgaacc agaaacagac cagaatatta cactagacga tttaggaatt taaggaggaa 4621 aaaacatggc tgacaaaatc acagaacaag atgttcttcg tgccacaaat gtagaaacac cagtacaatt 4691 aatgactgct atttataata gttcatcatc tctttttcag gcgaacgtac Ctatgccaaa tgcagataac WO 00/32825 PCT/IB99/02040 313 4761 atcgaagcgg ttggtgcagg gatcacacgt ttagacgtag taaaaaacga atttatttca actttagttg 4831 accgtattgg taaagtagtt atccgataca aatcttggcg taaccctttg aaaatgttta aaaaaggaaa 4901 catgccttta ggtcgaacga ttgaagaaat ttttgttgac attgcacagg aacataagtt caaccctgac 4971 gagtctgtta caggggtatt taaacaggaa gttcccgatg taaaaacatt gttccacgaa attaatcgtg 5041 aaggttacta caaacaaacg atccaagaag catqgttaga aaaagcattt acttcatggg ataatttcaa 5111 tagtttcgtt gctggtgtaa tgaacgcttt atacacaggt gacgaagtaa gcgaatttga atacacgaaa 5181 ttattaatag caaactacca agaaaaagag ctattcaaag agatcgaaat tggcgaaatt actgaatcaa 5251 atgcaaaaga atttatccgt aagatcaaat caacetctaa Caaattagaa tttatgagtt ccgcttacaa 5321 cgctcaagga gttaaaacat ctacctcaaa atctgatcaa tacgttatta ttgacgccga cacagacgca 5391 accattgacg ttgacgtttt agcagcggca ttcaatatga gtaaaactga ctttgtagga cacaaaatcg 5461 ttattgatga gtttcctaaa aaagaaggcg aagaatcgtc aaatattgtg gcagttattg tagatagtga 5531 atggtttatg atctacgaca aattgtacaa aacaacaagt ctatacaacc ctgaagggtt atattggaat 5601 tattggttgc accaccacca actatattct acttctcaat tcgggaacgc tgttgctttt gttaaatcag 5671 caacaaaacc tgtcacaaaa gttgcttttg caagtgcaac aactagtgtt gttaaaggat catctaaaga 5741 tatcgcattg acatttacac cagtagaagc aacaaaccaa caaggagaag ttgtttcatc agcaccagca 5811 ttggttaagg caaccgtaaa acaaacagca ggtaaagcga ctgccgtaac cgtagaaggc ttagaagtcg 5881 gtcaatcatt agtaacattc acagctatcg gaggtcaaca agcaacggtt cttgttacgg ttacttctga 5951 ctaaggagga caattatggc aagaaggtat acaaatgtaa aattgttggc taacgtgcct tttgataaca 6021 cctatacaca cacaagatgg tttaaaactc aacaggaaca ggaatcgtac tttaattcgt ttcctgttct 6091 taacgagaat agagattgtt cttatcaaag ggatacacaa ctcgggggag tttttagagt agataaacac 6161 aaagacgcct tatatgcttg taactatctc atctttaaaa acgaagaaac ttatcctagt aaatggcagt 6231 atgcctttgt tactgatatt gaatataaga atgacaacac aagtttcgtt acctttgaaa ttgatgtttt 6301 acaaacttat cgtttcgata ttggtatacg agaaagtttc attgcaaaag aacaccctca actttattat 6371 tcgaatggaa tacctttcat taatacaatt gaagagtcgc ttgattacgg tagagaatac acaacaacaa 6441 atgtaacaac ttttcatcct aacgatggag tcaattttct tgttattcta acaagtgaag caatgccagt 6511 tggagataag gaagataaat caggaggatc aatagtaggt ggcccatctc ctttttccta ttatttactt 6581 cctatcaatt caagtgggga ggtatacaaa ccaaatgggg caggcaatgc taattttgga gagtacatgg 6651 cgtttcttac aacgaaagaa ccttttttaa ataagatagt cgggatgtat gtaacgtcgt atacaggtat 6721 accattcatt gtggatcacg cgaacaaaac ggtaaggtat aatgcaggag gttcttataa gatcatgctt 6791 ccaacctacg ctagtgatcc aacaggaaca atgaaaacat tcgctttctt ttgtgtaaaa gaagcaagaa 6861 cattcgtacc taaaagaatt gatcttgtag ggaacgtgta taactacttt agagaagctt ttccgtttaa 6931 tgttaaggaa tcaaaactat ttatgtatcc ctattgttta atagaaatta cagatacaaa aggacatgta 7001 atgactttaa gacctgaata tcttacaggt ggtaaattga gtgtatatgt aaaaggttcg ttaggaattt 7071 ctaataaagt gatgatcgag ccgattgatt atgatgtaag taactcaacc attattacca atttaagtga 7141 caagatgtta atcgataatg atcctaacga tgtaggagtt aaatctgact atgcttctgc attcatgcaa 7211 ggaaacaaaa actccttgat tgctcaagag caaaacattc gcaatacttt cagacatggt atgggaaaca 7281 gtgcaatgag tacaggagga gcgatctttt cagccttagc aagtaacaac ccttttgttg gtttgactaa 7351 catcatggga gcaggacaac aagtaaacaa ctatgtttct gaaaaagaaa acggtttgaa cctcttggca 7421 ggtaaagtgg cagatatcga aaatattcca gataatgtaa cacagcttgg atcaaactta tctttcacaa 7491 caggaaactt tcaaaactat tatcaattgc gcttcaaaca aattaaatat gagtatgcaa caagacttga 7561 tcgttacttc tcaatgtatg gcacaaagag caatcgagta gctacaccaa acttacaaac aagaaaagca 7631 tggaatttca ttaaattaaa agaaccaaat attgtaggca caatgagtaa cgatgtatta acacgtgtga 7701 aacaaatttt tagtgcaggc gttacgcttt ggcatacgaa tgatgttttg aattataacc aagacaacgg 7771 agatgtatag gaaggaggaa taagatgagt agacgaaaag gtgcaggact tgctagaaat aaccgttata 7841 cagcaaaaag cagaccttat ccaaatgaac cctattcaag tgatgtagaa gaaatcagct actatgaaca 7911 ttatcgtaga caactcacgc tccttacgtt tcagttgttt gaatgggaaa atttgccaaa atcaattgac 7981 cctcgttatt tagaaattgc tttacacact aatggttatc ttggtttctt taaagaccct acacttgggt 8051 tcatggtttg cgcaggggca gaagatggtc aaatcgatca ttatcacaac cctattttct ttacagcaaa 8121 cgaagcaatg tatcacaaga gatatcctgt tttaagatat gatgatgatg atgataaatc aaaatgtatc 8191 atgttgtata ataatgactt gaaagttcct acgttaccaa gtttacatcg ttttgcttta gatatggcgg 8261 acataaacca gatatcacga gtgaatcgaa gagcgcaaaa aacacctgta attattcaaa ctgatgaaaa 8331 gaaatacttc tcattgctac aagcttataa ccaaattgac gaaaataatc aggctgtttt tgtggataaa 8401 gatatggagt ttgacgaatc ttttaatgta tggcaaacaa atgctccata tgtagtagat aaactacgat 8471 cagaattgaa cgaagtatgg aatgaagtgt taacttttct aggtatcaac aatgctaacg tagataagac 8541 tgcacgtgta caaacatcag aagtcttatc taacaatgaa cagattgaaa gttcaggtaa catcttgtta 8611 aaatcaagaa aagagttttg cgatcgtgta aatcgtgtct ttggcgatga acttgacgga aagattgacg 8681 tgaagtttag aacagacgcc gttcgacaat tacaactggc ggcaggtcaa tcaaaaaaag accagatgag 8751 tggagggttg ccaagtgcta cttaaacgtt atattgaaag tttcacttat taccaacctg aattatctcg 8821 aaaagaacgt attgaagttg gccgaaaaca attgtttgat tttgattatc cgttttatga cgaaacaaaa 8891 cgagcagaat ttgaaacaaa atttatcaat cacttttact tgagagagat aggctcagaa acgatgggat 8961 catttaagtt taatcttgac gaatatttaa atctaaacat gccctattgg aataaaatgt tcctatcaaa 9031 tcttgaagag tttccgattt ttgatgacat ggactacacc attgatgaga aacagaaatt gttaaatgag 9101 attgatacaa acatcaaagc gaatcgtgat gaatcgaaga accaaacgaa gcaagtagat caaacagaca 9171 acagaaacaa aaatacacgt gacacaggaa caaccgattc tttctcaagg aacacttata cagacacccc 9241 tcaaaaagat ttgagaattg ccagcaatgg agatggaaca ggtgtaatca attatgcaac aaatatcaca 9311 gaagatttga gtaaagaaac aacaagctcc acaggcgttg aaacaaacaa cgacaaaaca aatcaaaata 9381 cacgaagcaa tgcttctgaa aaagaaacaa agaacacaga cattaataaa gatcaaaatc aaaccaaaga 9451 tacgattaca cgatataaag gtaaaaaggg aaacactgat tatgctgact tactcgaaaa atatcgtaga 9521 agtgttttga gaattgagaa aatgatcttt agagaaatga acaaggaagg cttatttctc cttgtttatg 9591 gagggaggta gcaacaatgg tagattttaa ccccgacaag cggtttgacg gtttacccgc tgtattcaaa 9661 gaacgcttta gcaaatatcc tcatactgaa tacagataig aattactatt agatgaagaa gtatcggctt 9731 taattgccta tctgaatgaa gttggtgctt tagttaatga tatgagtggt tatttaaatt actttatcga 9801 acattttgtt gagaagttag aagagatcac aaatgacaca ctcaaaaaat ggttgtctga tggtacgtta 9871 gaaaatttaa tcaatgatac tgtttttgca aattatatca aagaaatcaa aagattacaa atcttggttg 9941 ctgaaacacg tgctaacagt gtgaatattc ttttgacaaa aaataaaccg gatgttgctg atgatcgaac 10011 attttggtat aagattCaaC gcgacaataC tgattatgga gccgatccta ttgacacgtt acgtattgtt WO 00/32825 PCT/IB99/02040 314 10081 gcaatcaata aagttagtgg ctggaatacc gctacaggag atatttatct taacattaaa ggaacggagg 10151 gtgtataatg gcagacatta gaacacaact aacaagtgaa gatggatcag acaatttatt tccaatttca 10221 aaagccgtta atattatgac taatagcggt acgaatgtag aaggagaatt gggtacactc aaacaaaatg 10291 acgaaacaat gaatacctca gttcaaaatg ctgtagttac tgccaatcaa gcaaaagatt ctgtagctga 10361 attaaatgta aatgttggta aactaaccaa tcgaataaca acattagaga gtacagtggc taatcttgat 10431 ggtattcgtt atgtagaggt gtaatatggc agataaaaat attcaaatgc aggataaaga tcataatcgt 10501 ttaatgcctg ttacaattgc taaaaatgtt ctaacaggcg actctaatct tgaattagtt aatgctgaaa 10571 taagaggtaa cgctagtgaa gctaaaacac ttgcacaaca agctaaagaa actgctgctg gtttgtcaac 10641 agaaattgac acagtaacat caaccgcaaa tcaagcgttg acgaaggctg gtacagcaca acaaaccgca 10711 gaacaagcga aaacaacagc aaacagtatc agcgcagttg caacggcagc taaaaacaca gctgattcag 10781 cacaaaaaag tgcaactgat ctagctgttc gagtaagcag tttagaggac acagcaatac aatatactgt 10851 attaccatag gaggaaaaat aatggcaaat aaaaatattc aaatgaagga tagcaatgac aataatttat 10921 atccaagtgt tcgagcagaa aacttgttag atttgaccag tcgtgctgaa ttaacaatga caaattgtca 10991 attatatgca gctggtgata aaacaaatgc aatctcttat ctcggtgcag taggtatgct cgaaggtatg 11061 ataaagttta ctgaaagttt gacaaaccct gtgatcacaa cgctaccaga aggttttaga ccaataagaa 11131 caaaacgtat tggttgtttc gcaaaatatt acacaccaaa tccaacagat acaaaagaaa tggtttatgt 11201 atcaatcaca cctgatggca aagtaactgt aaatgacaat gtaggtaaaa tcgaatatct atccctagat 11271 aattgcgttt tccctctaaa ataaggaggt tcatatggaa gaacgaattg atattcaaat gaacaagatg 11341 aaagaagaaa atcaaaagaa ttacctattg caccctgaaa cgaacccgaa acaagttgtt tttgatgaaa 11411 cattgcatgg aaatgaaaat caggagagtt tcaacaattt tgttgacaca agaaaaatga caactacaat 11481 tgatgtaagt gcttatgggg ttatcgctga cggtgtaaca gattgtacac caatattaaa taaattactt 11551 gaagaaaaaa gcgaaatggg tatcactttt tattttcctc cttgtgaacg tgattcatat tatcgctttg 11621 ctaacaccat tgaattgaaa cgtgatgtac ctgtagttac tttcttagga tcgggagaaa cgacattaaa 11691 gtttgaaaca atgacggcat ttaatgtaaa catcgaaagt ttcaatattg atggttttgc attatggttg 11761 ccacaaggcg ctcaaagtgg taaaggaatt ttctttaatg atactcgcaa ttacaatcgt tttgactttg 11831 atttgtttgt tcgtaactgt actttaaatg aaggaacgta tgttgttgtt gctagaggta gaggggttac 11901 atttgaaaat tgtctattct ctaatatctc tcaagcaatt atcaaaacag cttttcccga tgtaaatggt 11971 atgtggcaag ggaacgatat caatactagg ggtacaggtt ttagaggttt ctttgtgaaa aacaaccgta 12041 ttcatttttg tacagcgatc attatcgaca atgacgatga ttatcagaat gtaattaatt tctgtgaaat 12111 ttctggtaac acaatcgaag gtggcgtaag ttattatcga ggatatgcgc ataacttgca tgtccaaaac 12181 aacaaccatt ttctagcata cggaaataga aacgctttgt ttgagtttca agatgtggat caagcttata 12251 ttgatgtaga tgtttattgt cgtaactcac aagtcgaggg aatgaatagt acagctattt cacgtttaat 12321 tgttgtttac ggacattacc gaaacttaaa gattacaggt aaattatatc gttgtcaagg acatgttatc 12391 acgttgtatg gcggtggcgt taatttctat tgtgacttga tggcacaaga agcacctttg acggacggtt 12461 accggtttat tcaaacggct gacaatcgag ttaactatga tgggtttgtt gttcgtggtt tgtctaattc 12531 aacaaaagta aatacaccaa tgatctataa agcacctcag actgttttct ataatcgtag aatcgatcat 12601 gtgctaacag gtccaaatgc aagtaatgta tataactagg aggatatgag atggcaactc ttacaaatga 12671 acaaatagct agaggacaaa caatcgctaa aatactttca aaatatggct ataataaaaa ttcacaagta 12741 ggagttgtcg ccaatctcca ttgggaatcg gctggtttga acccgaacag caatgaatat ggtggaggcg 12811 gatatgggtt aggtcaatgg acgcctaaaa gcaatcttta tcgccaagca caaatttgtg ggttgtctaa 12881 tgctaaagct gaaacgttgg aaggtcaagc agagatcatc gctcaagggg ataaaacagg tcaatggatg 12951 gataatacac ctgtttcttc tgcaggttat actaaccctc agaccctttc agcatttaaa caatctgcaa 13021 atattgatgt tgctacaatt aattttatgt gtcactggga acgccctggt aaacttcata tcgaagaaag 13091 acttgatctt gcacaagctt atagtaagca tattgacggt agcggtggcg gtggcgtaaa acgttgctat 13161 ggaaccccaa tcaagaatac aaatcttgat cctaaaagtt tcatgagtgg acaacttttt ggCacgcatg 13231 caggaaacgg cagaccaaat aatttccatg atggtttgga ctttggttca attgatcacc ctggcaatga 13301 aatgattgca tgttgcgatg gaacagtaac acatgttgga aaatgggag cattaagagc gtattttgtg 13371 ataaatgatg gtacttacaa tatcgtttat caagaattta gttataacca gtcaaatata aaggtaaaag 13441 ttggcgacaa agttaagaac ggacaagttt gcgcaatacg tgacgcggat catttacatt taggttttac 13511 taaaaaagat tttatgactg cgttaggatc ttctttcata gatgatggaa catgggaaga ccctttgaag 13581 tttttagggc aatgttttgg agatggagat actggcggag ataatgacga taacaataag gataaaaatg 13651 atcttattta tctattgcta tccgatgcct tgaatggttg gaaattttaa taaggagaaa aaggtatgat 13721 agaatatatc acacaatggt tggcagatga taatcatctt gtttatggtt tgattatatg gttaatggtt 13791 gcaatgatta tcgattttgt gttaggtcc acaattgcca aatttaacaa ggaaatcgac tttagtagtt 13861 ttaaagctaa agcaggtatc attgttaagg tggcagaaat ggttttagtg gtttacttta ttcctgtagc 13931 agtaaaattc ggtgcagtag gtattacaat gtatataaca atgttggttg gtttgatttt atcagaaatt 14001 tatagtatac taggacatat ttcagatatc gatgatgata ataattggac tgattatgtt aagaagtttt 14071 tagacggaac actcaacaga aaggacgata ttaaatgatg aatggtattg atatctctag ttatcaaaca 14141 ggaattgatc tttcaaaagt tccatgcgat tttgtaaata ttaaagcaac aggcggaaca ggttatgtaa 14211 accctgattg tgaccgagca tttcaacaag ctttgtcttt aggtaaaaag attggtgtgt atcattttgc 14281 gcatgagagg ggtttagaag gtacacctca acaagaagcg caattctttt tagataatat taagggttac 14351 attggtaaag ctgttcttat tcttgacttt gaagggtcaa atcagaaaga tgtaaattgg gcgaaagcat 14421 ttcttgatta tgtttataat aaaacaggcg ttaaagcatg gttttatacg tatacagcaa acctcaatac 14491 aactgatttt tctagtattg caaaaggcga ttatggttta tgggttgctg aatatggatc aaatcaacca 14561 caaggctact ctcaaccagc gccacctaaa acaaataatt ttccaattgt tgcctgtttt cagtttacaa 14631 gtaaaggacg tttaccagga tacaacggca atcttgattt gaatgttttc tatggcgatg gtaatacatg 14701 ggatctgtat gtaggtaaaa aacaggatca aattgttcct cctgaaaata aaatatttga cgccacaagt 14771 gatgagttta ttttcactct tacaacaggt agcacaagcg tgttttattt tgacggagaa acgatctttg 14841 aattgtctga tccaacacaa ctcgatcata ttagaggaac atacaatcat gttcatggaa aagaaatcc 14911 atcaatggtg tggacacctg aacaatttga tatttactta aaaatgtatg aaaagaaacc agtatata 14981 taggagtgta tagtatgaca aatagcttag gcgttaaact tgaagagaaa aacttatact ataaccctaa 15051 caatgcttta ggttttaatt gcctaatgtt gtttgtaata ggcgcacgtg gtataggtaa aacttatggt 15121 tataaaaaat ttgttgttaa tcgctttatt aaacacggcg aacaatttat ttatttaaga agattcaaaa 15191 cagaacttaa aaagattcct caatttttca aaacaatggc gaaagaattt cctgatcata aacttgaagt 15261 aaaaggaaaa gaattctatt gtgatgataa attaatgggt tgggctgttc cacttagtac gtggggaatt 15331 gaaaaatcta atgaatatcc cgaagttcgt acaattttgt ttgatgagtt tttaattgag aaatcaaaaa WO 00/32825 PCT/IB99/02040 315 15401 tcacttattt accaaacgaa gctgaagcct tattgaacat gatggaaacg gttttccgaa gacgtacaaa 15471 tacaagatgt gttatgttga gtaatgcaac tagtgtagtg aacccttatt tcttgtattt caatctgcag 15541 ccagatttga ataagcgttt taatctatat caagatcgag gtatattgat tgaattgtgt gattcaaaag 15611 actttgcaga agtgaagaga gaaacacctt ttggtagatt gattcgtgga acagaatacg aagattttag 15681 tatcaacaat gagtttgtca atgatagtga tacgtttatt gaaaagagaa gtaaaaatag tagtttctta 15751 tgcgccattg cttttgaagg gaaaatcttt gggtattgga tagacgctga aacaggttgt gtctatgtga 15821 gttatgatta tcaaccaaat acaaatcatt tttatgcaat gactacgaaa gaccatgaag aaaatagatt 15891 gctgatgaaa aattggcgaa ataattatta tctttcaaca gtggcgaaag cattcaagaa tagttatctg 15961 cggtttgata acattgttat taagaattta cattatgatt tgtttaataa gatgaaaatc tggtaaccct 16031 attttagtag agctaccacg attagttcta ttacaatgat gaatagtaga taacatagta attgtagtct 16101 gcgatagttt tgttttggtt ctttggcgtt agtgattttt gctaacgcct ttttgtttgc ttttggatcg 16171 ggtgtgttaa tgtagacgaa atcttttctc atagttcttt ctccttatac agttttaata attccctgta 16241 aaatgtagct ataggacgtc catttctttc tattctaacg caattcacta tatccatttc taggtatata 16311 cggctatatt ttaatgcttt tgttaaggtg agaggttcgg ttttgtgtat caaaacctcc caaccatcta 16381 tataaaatac tgtgatatcg tatattggtt ccttgtagaa tgtagccatt attccacctc ctttaaatag 16451 ccttttggta tttgtaacgc taactgatag cgagaaccaa cttttacgta tgaagttact aatttcattg 16521 cctgacaata cttttcaaga atgttaaatt gactcgattc gggtaatagc gttgaatgag ttaacaaaag 16591 ttcggtgata tttatttccg gaacgtcgaa atcttgtaaa gtcccctcta tgatctctat tttttcattg 16661 tctgaaaggt tacgtttaca gtagaaacgt aaccattcaa ttagttcgcg gtgttctttg aatgttcgtg 16731 caatcatttt aattcctcct atttgtccgt aatttgttta tatccgtcat gtttcaattg ttccgcatag 16801 tgttcaacgc ttttcattga tttcgttatt gcgatattaa tgcaatggct atcaagataa acatagttat 16871 atttatcatg tgttaacacg aactcttttg taacgtaatc aatgtataaa attaattgtt ttcctccttg 16941 tgttatttct gacttgatag acgctaaact atcgttgtca tctttagtta gttgatttaa accctctaaa 17011 attaatgata aattgttaat catgtaaaac actcctttta tattaatttg atattgatac caccaatcga 17081 ataagattgg tagcattgta tcgaattaat atgttatttc tgtagttttc catgaatact cggaaataag 17151 atccatatct aattccttta gttcttcaaa agataacaaa caatattcct catcgcctac ctcatcaata 17221 tcaataagat aatgtttatt gttttcggta tctatgatat gataattcat atcccactca ttaaaggggt 17291 gaagtagaga tacctctcct ttttcagcta ttaatgattt attgttcata tgaaacactc cttttatatt 17361 aatttgatat tgataccacc aatcaaatgt gattggtagc attgtattaa attaatattc tggataattt 17431 attgagaaag tccagttatc atcaaatgaa attgttttat tttcaagtaa ctttttagcc tcatccacct 17501 caaattctaa atagaggaat ttactaagtt tatcctcatc tctaaaaatt ttcatacata ccacgttatt 17571 tgaataaatt tctgtgtata cgatcggttc attcatgttt atcatccttt ctttattaca tatatagtat 17641 atcatgtatt tacatatatg tcaatcattt aattcattta ttttaatgat ttatttgatt gtttttttat 17711 gatcctttct ttattacatc tatattatat catgtatgat tgtatttgtc aacaattaaa ttcatataaa 17781 tgtagtttgg ggtcagttac atttgtgtta tcaaaaaaag ataatattct att WO 00/32825 PCT/IB99/02040 316 Table 22 Phage 182 ORFs list nb Name Frame Position Key words 1 1 1820RF001 2 5966..7780 1 604 Tail protein; 2 | 1820RF002 | 1 | 2152..3873 1 573 DNA polymerase; 3 1820RF003 1 | 11305..12639 I 444 4 1820RF004 3 4626..5954 i 442 Major head protein; 5 1820RF005 3 | 12651..13700 1 349 Glycyl-Glycine endopeptidase; Lysostaphin precursor; 6 1820RF006 1 14995..16026 1 343 1 Encapsidation protein; ATG/GTP-binding site motif A; 7 1820RF007 1 7795..8775 I 326 i Upper collar protein; 8 1820RF008 2 14105..14983 1 292 | Lysozyme; Muramidase; 9 1820RF010 2 1310..2155 | 281 ; Terminal protein; 10 1820RF009 2 | 8765..9601 1 278 1 Lower collar protein; 11 [ 1820RF011 1 9607..10158 1 183 1 Pre-neck appendage protein; 12 1820RF012 3 | 10872..11294 1 140 ! 13 1820RF013 1 10456..10860 1 134 | 14 | 1820RF014 3 13716..14108 - 130 1 Lysis protein; 15 | 182ORF015 2 854..1225 1 123 I Early protein; 16 182ORF018 -2 16429..16737 1 102 1 17 1820RF020 3 10158..10454 1 98 I Leucine-zipper motif; 18 1820RF019 3 4323..4613 | 96 1 Head protein; 19 1820RF016 -3 16749..17033 | 94 _ 20 | 1820RF022 1 12868..13149 1 93 _ 21 | 1820RF023 -2 11914..12189 91 _ 22 1820RF017 1 154..426 90 | 23 1820RF024 | 3 6174..6446 1 90 | 24 | 1820RF025 2 548..814 88 i Early protein; 25 | 1820RF026 | -3 12999..13259 86 | 26 1820RF027 1 -1 14642..14896 84 1 27 1820RF028 3 14430..14672 80 T 28 1820RF021 -3 17106..17339 . 77 | 29 - 1820RF030 -1 16199..16429 76 ! 30 - 1820RF031 -3 8379..8603 1 74 | 31 | 1820RF032 -1 11195..11413 1 72 _ 32 | 1820RF033 -1 4727..4942 | 71 _ 33 | 1820RF034 -1 5951..6160 | 69 _ 34 | 1820RF029 -3 17412..17606 64 1 35 1 1820RF035 -3 15570..15758 1 62 1 36 1820RF036 -3 1 2127..2315 1 62 | 37 1 1820RF037 -1 1 12095..12280 1 61 i 38 1 1820RF038 3 | 14769..14951 60 1 39 1820RF039 2 9992..10171 59 1 40 1820RF040 -3 16029..16202 57 1 41 1820RF041 1 | 3886..4056 56 1 Early protein; 42 | 182ORF042 -3 | 10671..10832 53 | 43 1 1820RF043 | -3 | 10491..10652 53 | 44 1820RF044 -1 6299..6457 52 45 1820RF045 -2 6571..6729 52 46 1820RF046 2 2372..2527 51 47 1820RF047 -2 13201..13353 50 48 1820RF048 -3 3243..3395 50 | 49 1820RF049 3 | 1578..1724 48 1 50 1820RF050 2 8012..8155 47 1 51 1820RF051 3 9390..9530 46 1 52 1820RF052 1 4096..4233 | 45 53| 1820RF053 2 15656..15793 | 45 54 1820RF054 -2 8002..8136 | 44 55 | 1820RF055 2 8324..8455 |43 56 | 1820RF056 3 6549..6680 43 I 57| 1820RF057 -3 8133..8264 43 1 58 j 1820RF058 -1 5048..5176 42 I 59 1 1820RF059 -2 15748..15876 42 1 60 1820RF060 -3 15276..15404 42 61 1820RF061 .- 3 1974..2102 42 62 1820RF062 -2 1867..1992 41 1 63 1820RF063 -3 14181..14306 1 41 1 64 1820RF064 -2 7234..7356 L 40 WO 00/32825 PCT/IB99/02040 317 65 1 1820RF065 -2 F 3460.3582 1 40 66 71820RF066 1 4234.4353 1 39 67 1 1820RF067 -1 13763..13882 39 68 1 1820RF068 -1 7148..7267 ____ 39 _____________________ 69 | 1820RF069 -3 4908.5027 1 39 -70~ 71820RF070 -3 1 912..1031 1 39 1 711 182ORF071 2 11741..11857 1 38 72 | 1820RF072 -3 11610.11723 1 37 73 | 1820RF073 -3 2763..2876 1 37 74 1 1820RF074 -1 8813..8923 1 36 75 182ORF075 -3 7353..7463 1 36 76 f 1820RF076 -3 2316..2426 36 77 | 1820RF077 2 11858.11965 1 35 78 1820RF078 -2 7564..7671 35 1 79 1820RF079 -2 7381.7488 1 35 80 L1820RF080 [ -2 4372..4473 j 33 WO 00/32825 PCT/IB99/02040 318 Table 23 Predicted amino acid sequences of ORFs from phage 182 1820RF001 5966 atggcaagaaggtatacaaatgtaaaattgttggctaacgtgccttttgataacacctatacacacacaagatggtttaaaact 1 M A R R Y T N V K L L A N V P F D N T Y T H T R W F K T 6050 caacaggaacaggaatcgtactttaattcgtttcctgttcttaacgagaatagagattgttcttatcaaagggatacacaactc 29 Q Q E Q E S Y F N S F P V L N E N R D C S Y Q R D T Q L 6134 gggggagtttttagagtagataaacacaaagacgccttatatgcttgtaactatctcatctttaaaaacgaagaaacttatcct 57 G G V F R V D K H K D A L Y A C N Y L I F K N E E T Y P 6218 agtaaatggcagtatgcctttgttactgatattgaatataagaatgacaacacaagtttcgttacctttgaaattgatgtttta 85 S K W Q Y A F V T D I E Y K N D N T S F V T F E I D V L 6302 caaacttatcgtttcgatattggtatacgagaaagtttcattgcaaaagaacaccctcaactttattattcgaatggaatacct 113 Q T Y R F D I G I R E S F I A K E H P Q L Y Y S N G I P 6386 ttcattaatacaattgaagagtcgcttgattacggtagagaatacacaacaacaaatgtaacaacttttcatcctaacgatgga 141 F I N T I E E S L D Y G R E Y T T T N V T T F H P N D G 6470 gtcaattttcttgttattctaacaagtgaagcaatgccagttggagataaggaagataaatcaggaggatcaatagtaggtggc 169 V N F L V I L T S E A M P V G D K E D K S G G S I V G G 6554 ccatctcctttttcctattatttacttcctatcaattcaagtggggaggtatacaaaccaaatggggcaggcaatgctaatttt 197 P S P F S Y Y L L P I N S S G E V Y K P N G A G N A N F 6638 ggagagtacatggcgtttcttacaacgaaagaaccttttttaaataagatagtcgggatgtatgtaacgtcgtatacaggtata 225 G E Y M A F L T T K E P F L N K I V G M Y V T S Y T G I 6722 ccattcattgtggatcacgcgaacaaaacggtaaggtataatgcaggaggttcttataagatcatgcttccaacctacgctagt 253 P F I V D H A N K.T V R Y N A G G S Y K I M L P T Y A S 6806 gatccaacaggaacaatgaaaacattcgctttcttttgtgtaaaagaagcaagaacattcgtacctaaaagaattgatcttgta 281 D P T G T M K T F A F F C V K E A R T F V P K R I D L V 6890 gggaacgtgtataactactttagagaagcttttccgtttaatgttaaggaatcaaaactatttatgtatccctattgtttaata 309 G N V Y N Y F R E A F P F N V K E S K L F M Y P Y C L I 6974 gaaattacagatacaaaaggacatgtaatgactttaagacctgaatatcttacaggtggtaaattgagtgtatatgtaaaaggt 337 E I T D T K G H V M T L R P E Y L T G G K L S V Y V K G 7058 tcgttaggaatttctaataaagtgatgatcgagccgattgattatgatgtaagtaactcaaccattattaccaatttaagtgac 365 S L G I S N K V M I E P I D Y D V S N S T I I T N L S D 7142 aagatgttaatcgataatgatcctaacgatgtaggagttaaatctgactatgcttctgcattcatgcaaggaaacaaaaactcc 393 K M L I D N D P N D V G V K S D Y A S A F M Q G N K N S 7226 ttgattgctcaagagcaaaacattcgcaatactttcagacatggtatgggaaacagtgcaatgagtacaggaggagcgatcttt 421 L I A Q E Q N I R N T F R H G M G N S A M S T G G A I F 7310 tcagccttagcaagtaacaacccttttgttggtttgactaacatcatgggagcaggacaacaagtaaacaactatgtttctgaa 449 S A L A S N N P F V G L T N I M G A G Q Q V N N Y V S E 7394 aaagaaaacggtttgaacctcttggcaggtaaagtggcagatatcgaaaatattccagataatgtaacacagttggatcaaac 477 K E N G L N L L A G K V A D I E N I P D N V T Q L G S N 7478 ttatctttcacaacaggaaactttcaaaactattatcaattgcgcttcaaacaaattaaatatgagtatgcaacaagacttgat 505 L S F T T G N F Q N Y Y Q L R F K Q I K Y E Y A T R L D 7562 cgttacttctcaatgtatggcacaaagagcaatcgagtagctacaccaaacttacaaacaagaaaagcatggaatttcattaaa 533 R Y F S M Y G T K S N R V A T P N L Q T R K A W N F I K 7646 ttaaaagaaccaaatattgtaggcacaatgagtaacgatgtattaacacgtgtgaaacaaatttttagtgcaggcgttacgctt 561 L K E P N I V G T M S N D V L T R V K Q I F S A G V T L 7730 tggcatacgaatgatgttttgaattataaccaagacaacggagatgtatag 7780 589 W H T N D V L N Y N Q D N G D V * 182ORF002 2152 atgattaagaaatatactggcgactttgaaacaacaactgatctcaacgattgtcgtgtatggtcgtggggcgtatgcgatata 1 M I K K Y T G D F E T T T D L N D C R V W S W G V C D I 2236 gacaacgttgacaatatgacgttcggtttagaaatcgattctttttttgagtggtgtaaaatgcaaggcagcacagacatttat 29 D N V D N M T F G L E I D S F F E W C K M Q G S T D I Y 2320 ttccacaacgaaaaatttgacggagagtttatgctttcatggttattcaaaaatggtttcaaatggtgtaaagaagcaaaagaa 57 F H N E K F D G E F M L S W L F K N G F K W C K E A K E 2404 gatcgaacattctccacactcatatcaaatatgggtcaatggtatgctttggaaatttgttgggaagttaattacacaacaaca 85 D R T F S T L I S N M G Q W Y A L E I C W E V N Y T T T 2488 aaatcaggtaaaacgaaaaaagagaaatctcgaacaataatttatgatagccttaaaaaatatccttttccagtgaaacaaatt 113 K S G K T K K E K S R T I I Y D S L K K Y P F P V K Q I 2572 gcagaagcttttaattttcctataaaaaaaggcgaaatagattatacaaaagaaagacctattggttacaaaccaacaaaagat 141 A E A F N F P I K K G E I D Y T K E R P I G Y K P T K D 2656 gaatgggagtatttaaagaacgacattcagattatggcgatggcattaaaaattcaattcgatcaaggactaactcgaatgact 169 E W E Y L K N D I Q I M A M A L K I Q F D Q G L T R M T 2740 agaggaagcgacgctttaggcgattacaaagattggctaaaagctacacatggaaaatcaactttcaaacaatggtttcctatt 197 R G S D A L G D Y K D W L K A T H G K S T F K-Q W F P. I 2824 ttgtctttagggtttgataaagacttacgtaaagcatacaaaggcggcttcacttgggtaaacaaagtttttcaaggaaagaa 225 L S L G F D K D L R K A Y K G G F T W V N K V F Q G K E 2908 ataggtgacggcattgtctttgatgtcaactctttgtatccctctcaaatgtacgtaagacctttaccatatggaacacctcta 253 I G D G I V F D V N S L Y P S Q M Y V R P L P Y G T P L 2992 ttctacgaaggagaatacaaaccgaacaacgactatccgctgtacattcaaaatatcaaagtaagattccgtttaaaggagggt 281 F Y E G E Y K P N N D Y P L Y I Q N I K V R F R L K E G 3076 tatattccaaccattcaagttaagcaaagttcattattcattcaaaacgaatatcttgaatcaagtgtaaacaagttaggagtt WO 00/32825 PCT/IB99/02040 319 309 Y I P T I Q V K Q S S L F I Q N E Y L E S S V N K L G V 3160 gacgaattaatcgatcttactcttacaaatgttgacctagaattattttttgaacactacgatattttagagatacattacact 337 D E L I D L T L T N V D L E L F F E H Y D I L E I H Y T 3244 tacggatatatgttcaaagcttcttgtgatatgttcaaaggctggatcgataaatggatcgaagtaaagaacaccaccgaaggg 365 Y G Y M F K A S C D M F K G W I D K W I E V K N T T E G 3328 gctagaaaagctaacgccaaaggtatgttaaatagcttgtatggaaagttcggaacaaaccctgacattacaggaaaagtgcct 393 A R K A N A K G M L N S L Y G K F G T N P D I T G K V P 3412 tacatgggcgaggacggcattgttcgattgacactaggagaagaagaattaagagatcctgtttatgttccgcttgctagtttt 421 Y M G E D G I V R L T L G E E E L R D P V Y V P L A S F 3496 gtgacggcttggggtagatatactaccattacaaccgctcaaaaatgttttgatcgcattatttattgtgatacagatagcatt 449 V T A W G R Y T T I T T A Q K C F D R I I Y C D T D S I 3580 catctagtaggaacagaagttccagaagcaatcgatcacttggttgatcctaaaaaacttggttattgggggcatgaaagcaca 477 H L V G T E V P E A I D H L V D P K K L G Y W G H E S T 3664 tttcaacgagcaaaattcattcggcagaaaacatacgtagaagaaattgatggcgaattaaatgtaaagtgtgctggtatgcca 505 F Q R A K F I R Q K T Y V E E I D G E L N V K C A G M P 3748 gatcgaataaaagagattgtaacttttgacaattttgaagttggtttttcaagctatggaaagttgctacctaaaagaacacaa 533 D R I K E I V T F D N F E V G F S S Y G K L L P K R T Q 3832 ggtggcgtggtattagtagacacaatgtttacaatcaaataa 3873 561 G G V V L V D T M F T I K * 1820RF003 11305 atggaagaacgaattgatattcaaatgaacaagatgaaagaagaaaatcaaaagaattacctattgcaccctgaaacgaacccg 1 M E E R I D I Q M N K M K E E N Q K N Y L L H P E T N P 11389 aaacaagttgtttttgatgaaacattgcatggaaatgaaaatcaggagagtttcaacaattttgttgacacaagaaaaatgaca 29 K Q V V F D E T L H G N E N Q E S F N N F V D T R K M T 11473 actacaattgatgtaagtgcttatggggttatcgctgacggtgtaacagattgtacaccaatattaaataaattacttgaagaa 57 T T I D V S A Y G V I A D G V T D C T P I L N K L L E E 11557 aaaagcgaaatgggtatcactttttattttcctccttgtgaacgtgattcatattatcgctttgctaacaccattgaattgaaa 85 K S E M G I T F Y F P P C E R D S Y Y R F A N T I E L K 11641 cgtgatgtacctgtagttactttcttaggatcgggagaaacgacattaaagtttgaaacaatgacggcatttaatgtaaacatc 113 R D V P V V T F L G S G E T T L K F E T M T A F N V N I 11725 gaaagtttcaatattgatggttttgcattatggttgccacaaggcgctcaaagtggtaaaggaattttctttaatgatactcgc 141 E S F N I D G F A L W L P Q G A Q S G K G I F F N D T R 11809 aattacaatcgttttgactttgatttgtttgttcgtaactgtactttaaatgaaggaacgtatgttgttgttgctagaggtaga 169 N Y N R F D F D L F V R N C T L N E G T Y V V V A R G R 11893 ggggttacatttgaaaattgtctattctctaatatctctcaagcaattatcaaaacagcttttcccgatgtaaatggtatgtgg 197 G V T F E N C L F S N I S Q A I I K T A F P D V N G M W 11977 caagggaacgatatcaatactaggggtacaggttttagaggtttctttgtgaaaaacaaccgtattcatttttgtacagcgatc 225 Q G N D I N T R G T G F R G F F V K N N R I H F C T A I 12061 attatcgacaatgacgatgattatcagaatgtaattaatttctgtgaaatttctggtaacacaatcgaaggtggcgtaagttat 253 I I D N D D D Y Q N V I N F C E I S G N T I E G G V S Y 12145 tatcgaggatatgcgcataacttgcatgtccaaaacaacaaccattttctagcatacggaaatagaaacgctttgtttgagttt 281 Y R G Y A H N L H V Q N N N H F L A Y G N R N A L F E F 12229 caagatgtggatcaagcttatattgatgtagatgtttattgtcgtaactcacaagtcgagggaatgaatagtacagctatttca 309 Q D V D Q A Y I D V D V Y C R N S Q V E G M N S T A I S 12313 cgtttaattgttgtttacggacattaccgaaacttaaagattacaggtaaattatatcgttgtcaaggacatgttatcacgttg 337 R L I V V Y G H Y R N L K I T G K L Y R C Q G H V I T L 12397 tatggcggtggcgttaatttctattgtgacttgatggcacaagaagcacctttgacggacggttaccggtttattcaaacggct 365 Y G G G V N F Y C D L M A Q E A P L T D G Y R F I Q T A 12481 gacaatcgagttaactatgatgggtttgttgttcgtggtttgtctaattcaacaaaagtaaatacaccaatgatctataaagca 393 D N R V N Y D G F V V R G L S N S T K V N T P M I Y K A 12565 cctcagactgttttctataatcgtagaatcgatcatgtgctaacaggtccaaatgcaagtaatgtatataactag 12639 421 P Q T V F Y N R R I D H V L T G P N A S N V Y N * 1820RF004 4626 atggctgacaaaatcacagaacaagatgttcttcgtgccacaaatgtagaaacaccagtacaattaatgactgctatttataat 1 M A D K I T E Q D V L R A T N V E T P V Q L M T A I Y N 4710 agttcatcatctctttttcaggcgaacgtacctatgccaaatgcagataacatcgaagcggttggtgcagggatcacacgttta 29 S S S S L F Q A N V P M P N A D N I E A V G A G I T R L 4794 gacgtagtaaaaaacgaatttatttcaactttagttgaccgtattggtaaagtagttatccgatacaaatcttggcgtaaccct 57 D V V K N E F I S T L V D R I G K V V I R Y K S W R N P 4878 ttgaaaatgtttaaaaaaggaaacatgcctttaggtcgaacgattgaagaaatttttgttgacattgcacaggaacataagttc 85 L K M F K K G N M P L G R T I E E I F V D I A Q E H K F 4962 aaccctgacgagtctgttacaggggtatttaaacaggaagttcccgatgtaaaaacattgttccacgaaattaatcgtgaaggt 113 N P D E S V T G V F K Q E V P D V K T L F H E I N R E G 5046 tactacaaacaaacgatccaagaagcatggttagaaaaagcatttacttcatgggataatttcaatagtttcgttgctggtgta 141 Y Y K Q T I Q E A W L E K A F T S W D N F N S F V A G V 5130 atgaacgctttatacacaggtgacgaagtaagcgaatttgaatacacgaaattattaatagcaaactaccaagaaaaagagcta 169 M N A L Y T G D E V S E F E Y T K L L I A N Y Q E K E L 5214 ttcaaagagatcgaaattggcgaaattactgaatcaaatgcaaaagaatttatccgtaagatcaaatcaacctctaacaaatta 197 F K E I E I G E I T E S N A K E F I R K I K S-T S-N K L 5298 gaatttatgagttccgcttacaacgctcaaggagttaaaacatctacctcaaaatctgatcaatacgttateattgacgccgac 225 E F M S S A Y N A Q G V K T S T S K S D Q Y V I I D A D 5382 acagacgcaaccattgacgttgacgttttagcagcggcattcaatatgagtaaaactgactttgtaggacacaaaatcgttatt 253 T D A T I D V D V L A A A F N M S K T D F V G H K I V I 5466 gatgagtttcctaaaaaagaaggcgaagaatcgtcaaatattgtggcagttattgtagatagtgaatggtttatgatctacgac WO 00/32825 PCT/IB99/02040 320 281 D E F P K K E G E E S S N I V A V I V D S E W F M I Y D 5550 aaattgtacaaaacaacaagtctatacaaccctgaagggttatattggaattattggttgcaccaccaccaactatattctact 309 K L Y K T T S L Y N P E G L Y W N Y W L H H H Q L Y S T 5634 tctcaattcgggaacgctgttgcttttgttaaatcagcaacaaaacctgtcacaaaagttgcttttgcaagtgcaacaactagt 337 S Q F G N A V A F V K S A T K P V T K V A F A S A T T S 5718 gttgttaaaggatcatctaaagatatcgcattgacatttacaccagtagaagcaacaaaccaacaaggagaagttgtttcatca 365 V V K G S S K D I A L T F T P V E A T N Q Q G E V V S S 5802 gcaccagcattggttaaggcaaccgtaaaacaaacagcaggtaaagcgactgccgtaaccgtagaaggcttagaagtcggtcaa 393 A P A L V K A T V K Q T A G K A T A V T V E G L E V G Q 5886 tcattagtaacattcacagctatcggaggtcaacaagcaacggttcttgttacggttacttctgactaa 5954 421 S L V T F T A I G G Q Q A T V L V T V T S D * 1820RF005 12651 atggcaactcttacaaatgaacaaatagctagaggacaaacaatcgctaaaatactttcaaaatatggctataataaaaattca 1 M A T L T N E Q I A R G Q T I A K I L S K Y G Y N K N S 12735 caagtaggagttgtcgccaatctccattgggaatcggctggtttgaacccgaacagcaatgaatatggtggaggcggatatggg 29 Q V G V V A N L H W E S A G L N P N S N E Y G G G G Y G 12819 ttaggtcaatggacgcctaaaagcaatctttatcgccaagcacaaatttgtgggttgtctaatgctaaagctgaaacgttggaa 57 L G Q W T P K S N L Y R Q A Q I C G L S N A K A E T L E 12903 ggtcaagcagagatcatcgctcaaggggataaaacaggtcaatggatggataatacacctgtttcttctgcaggttatactaac 85 G Q A E I I A Q G D K T G Q W M D N T P V S S A G Y T N 12987 cctcagaccctttcagcatttaaacaatctgcaaatattgatgttgctacaattaattttatgtgtcactgggaacgccctggt 113 P Q T L S A F K Q S A N I D V A T I N F M C H W E R P G 13071 aaacttcatatcgaagaaagacttgatcttgcacaagcttatagtaagcatattgacggtagcggtggcggtggcgtaaaacgt 141 K L H I E E R L D L A Q A Y S K H I D G S G G G G V K R 13155 tgctatggaaccccaatcaagaatacaaatcttgatcctaaaagtttcatgagtggacaactttttggcacgcatgcaggaaac 169 C Y G T P I K N T N L D P K S F M S G Q L F G T H A G N 13239 ggcagaccaaataatttccatgatggtttggactttggttcaattgatcaccctggcaatgaaatgattgcatgttgcgatgga 197 G R P N N F H D G L D F G S I D H P G N E M I A C C D G 13323 acagtaacacatgttggaacaatgggagcattaagagcgtattttgtgataaatgatggtacttacaatatcgtttatcaagaa 225 T V T H V G T M G A L R A Y F V I N D G T Y N I V Y Q E 13407 tttagttataaccagtcaaatataaaggtaaaagttggcgacaaagttaagaacggacaagtttgcgcaatacgtgacgcggat 253 F S Y N Q S N I K V K V G D K V K N G Q V C A I R D A D 13491 catttacatttaggttttactaaaaaagattttatgactgcgttaggatcttctttcatagatgatggaacatgggaagaccct 281 H L H L G F T K K D F M T A L G S S F I D D G T W E D P 13575 ttgaagtttttagggcaatgttttggagatggagatactggcggagataatgacgataacaataaggataaaaatgatcttatt 309 L K F L G Q C F G D G D T G G D N D D N N K D K N D L I 13659 tatctattgctatccgatgccttgaatggttggaaattttaa 13700 337 Y L L L S D A L N G W K F * 1820RF006 14995 atgacaaatagcttaggcgttaaacttgaagagaaaaacttatactataaccctaacaatgctttaggttttaattgcctaatg 1 M T N S L G V K L E E K N L Y Y N P N N A L G F N C L M 15079 ttgtttgtaataggcgcacgtggtataggtaaaacttatggttataaaaaatttgttgttaatcgctttattaaacacggcgaa 29 L F V I G A R G I G K T Y G Y K K F V V N R F I K H G E 15163 caatttatttatttaagaagattcaaaacagaacttaaaaagattcctcaatttttcaaaacaatggcgaaagaatttcctgat 57 Q F I Y L R R F K T E L K K I P Q F F K T M A K E F P D 15247 cataaacttgaagtaaaaggaaaagaattctattgtgatgataaattaatgggttgggctgttccacttagtacgtggggaatt 85 H K L E V K G K E F Y C D D K L M G W A V P L S T W G I 15331 gaaaaatctaatgaatatcccgaagttcgtacaattttgtttgatgagtttttaattgagaaatcaaaaatcacttatttacca 113 E K S N E Y P E V R T I L F D E F L I E K S K I T Y L P 15415 aacgaagctgaagccttattgaacatgatggaaacggttttccgaagacgtacaaatacaagatgtgttatgttgagtaatgca 141 N E A E A L L N M M E T V F R R R T N T R C V M L S N A 15499 actagtgtagtgaacccttatttcttgtatttcaatctgcagccagatttgaataagcgttttaatctatatcaagatcgaggt 169 T S V V N P Y F L Y F N L Q P D L N K R F N L Y Q D R G 15583 atattgattgaattgtgtgattcaaaagactttgcagaagtgaagagagaaacaccttttggtagattgattcgtggaacagaa 197 I L I E L C D S K D F A E V K R E T P F G R L I R G T E 15667 tacgaagattttagtatcaacaatgagtttgtcaatgatagtgatacgtttattgaaaagagaagtaaaaatagtagtttctta 225 Y E D F S I N N E F V N D S D T F I E K R S K N S S F L 15751 tgcgccattgcttttgaagggaaaatetttgggtattggatagacgctgaaacaggttgtgtetatgtgagttatgattatcaa 253 C A I A F E G K I F G Y W I D A E T G C V Y V S Y D Y Q 15835 ccaaatacaaatcatttttatgcaatgactacgaaagaccatgaagaaaatagattgctgatgaaaaattggcgaaataattat 281 P N T N H F Y A M T T K D H E E N R L L M K N W R N N Y 15919 tatctttcaacagtggcgaaagcattcaagaatagttatctgcggtttgataacattgttattaagaatttacattatgatttg 309 Y L S T V A K A F K N S Y L R F D N I V I K N L H Y D L 16003 tttaataagatgaaaatctggtaa 16026 337 F N K M K I W * 1820RF007 7795 atgagtagacgaaaaggtgcaggacttgctagaaataaccgttatacagcaaaaagcagaccttatccaaatgaaocctattca 1 M S R R K G A G L A R N N R Y T A K S R P Y P NZ I Y S 7879 agtgatgtagaagaaatcagatactatgaacattategtagacaactcacgetecttacgtttcagttgtttgaatgggaaaat 29 S D V E E I S Y Y E H Y R R Q L T L L T F Q L F E W E N 7963 ttgccaaaatcaattgaccetcgttatttagaaattgetttacacactaatggttatettggtttctttaaagaccatacactt 57 L P K S I D P R Y L E I A L H T N G Y L G F F K D P T L 8047 gggttcatggtttgcgcaggggcagaagatggtcaaatcgatcattatcacaaccctattttctttacagcaaacgaagcaatg WO 00/32825 PCT/IB99/02040 321 85 G F M V C A G A E D G Q I D H Y H N P I F F T A N E A M 8131 tatcacaagagatatcctgttttaagatatgatgatgatgatgataaatcaaaatgtatcatgttgtataataatgacttgaaa 113 Y H K R Y P V L R Y D D D D D K S K C I M L Y N N D L K 8215 gttcctacgttaccaagtttacatcgttttgctttagatatggcggacataaaccagatatcacgagtgaatcgaagagcgcaa 141 V P T L P S L H R F A L D M A D I N Q I S R V N R R A Q 8299 aaaacacctgtaattattcaaactgatgaaaagaaatacttctcattgctacaagcttataaccaaattgacgaaaataatcag 169 K T P V I I Q T D E K K Y F S L L Q A Y N Q I D E N N Q 8383 gctgtttttgtggataaagatatggagtttgacgaatcttttaatgtatggcaaacaaatgctccatatgtagtagataaacta 197 A V F V D K D M E F D E S F N V W Q T N A P Y V V D K L 8467 cgatcagaattgaacgaagtatggaatgaagtgttaacttttctaggtatcaacaatgctaacgtagataagactgcacgtgta 225 R S E L N E V W N E V L T F L G I N N A N V D K T A R V 8551 caaacatcagaagtcttatctaacaatgaacagattgaaagttcaggtaacatcttgttaaaatcaagaaaagagttttgcgat 253 Q T S E V L S N N E Q I E S S G N I L L K S R K E F C D 8635 cgtgtaaatcgtgtctttggcgatgaacttgacggaaagattgacgtgaagtttagaacagacgccgttcgacaattacaactg 281 R V N R V F G D E L D G K I D V K F R T D A V R Q L Q L 8719 gcggcaggtcaatcaaaaaaagaccagatgagtggagggttgccaagtgctacttaa 8775 309 A A G Q S K K D Q M S G G L P S A T * 1820RF008 14105 atgatgaatggtattgatatctctagttatcaaacaggaattgatctttcaaaagttccatgcgattttgtaaatattaaagca 1 M M N G I D I S S Y Q T G I D L S K V P C D F V N I K A 14189 acaggcggaacaggttatgtaaaccctgattgtgaccgagcatttcaacaagctttgtctttaggtaaaaagattggtgtgtat 29 T G G T G Y V N P D C D R A F Q Q A L S L G K K I G V Y 14273 cattttgcgcatgagaggggtttagaaggtacacctcaacaagaagcgcaattctttttagataatattaagggttacattggt 57 H F A H E R G L E G T P Q Q E A Q F F L D N I K G Y I G 14357 aaagctgttcttattcttgactttgaagggtcaaatcagaaagatgtaaattgggcgaaagcatttcttgattatgtttataat 85 K A V L I L D F E G S N Q K D V N W A K A F L D Y V Y N 14441 aaaacaggcgttaaagcatggttttatacgtatacagcaaacctcaatacaactgatttttctagtattgcaaaaggcgattat 113 K T G V K A W F Y T Y T A N L N T T D F S S I A K G D Y 14525 ggtttatgggttgctgaatatggatcaaatcaaccacaaggctactctcaaccagcgccacctaaaacaaataattttccaatt 141 G L W V A E Y G S N Q P Q G Y S Q P A P P K T N N F P I 14609 gttgcctgttttcagtttacaagtaaaggacgtttaccaggatacaacggcaatcttgatttgaatgttttctatggcgatggt 169 V A C F Q F T S K G R L P G Y N G N L D L N V F Y G D G 14693 aatacatgggatctgtatgtaggtaaaaaacaggatcaaattgttcctcctgaaaataaaatatttgacgccacaagtgatgag 197 N T W D L Y V G K K Q D Q I V P P E N K I F D A T S D E 14777 tttattttcactcttacaacaggtagcacaagcgtgttttattttgacggagaaacgatctttgaattgtctgatccaacacaa 225 F I F T L T T G S T S V F Y F D G E T I F E L S D P T Q 14861 ctcgatcatattagaggaacatacaatcatgttcatggaaaagaaatcccatcaatggtgtggacacctgaacaatttgatatt 253 L D H I R G T Y N H V H G K E I P S M V W T P E Q F D I 14945 tacttaaaaatgtatgaaaagaaaccagtatataaatag 14983 281 Y L K M Y E K K P V Y K * 1820RF009 8765 gtgctacttaaacgttatattgaaagtttcacttattaccaacctgaattatctcgaaaagaacgtattgaagttggccgaaaa 1 V L L K R Y I E S F T Y Y Q P E L S R K E R I E V G R K 8849 caattgtttgattttgattatccgttttatgacgaaacaaaacgagcagaatttgaaacaaaatttatcaatcacttttacttg 29 Q L F D F D Y P F Y D E T K R A E F E T K F I N H F Y L 8933 agagagataggctcagaaacgatgggatcatttaagtttaatcttgacgaatatttaaatctaaacatgccctattggaataaa 57 R E I G S E T M G S F K F N L D E Y L N L N M P Y W N K 9017 atgttcctatcaaatcttgaagagtttccgatttttgatgacatggactacaccattgatgagaaacagaaattgttaaatgag 85 M F L S N L E E F P I F D D M D Y T I D E K Q K L L N E 9101 attgatacaaacatcaaagcgaatcgtgatgaatcgaagaaccaaacgaagcaagtagatcaaacagacaacagaaacaaaaat 113 I D T N I K A N R D E S K N Q T K Q V D Q T D N R N K N 9185 acacgtgacacaggaacaaccgattctttctcaaggaacacttatacagacacccctcaaaaagatttgagaattgccagcaat 141 T R D T G T T D S F S R N T Y T D T P Q K D L R I A S N 9269 ggagatggaacaggtgtaatcaattatgcaacaaatatcacagaagatttgagtaaagaaacaacaagctccacaggcgttgaa 169 G D G T G V I N Y A T N I T E D L S K E T T S S T G V E 9353 acaaacaacgacaaaacaaatcaaaatacacgaagcaatgcttctgaaaaagaaacaaagaacacagacattaataaagatcaa 197 T N N D K T N Q N T R S N A S E K E T K N T D I N K D Q 9437 aatcaaaccaaagatacgattacacgatataaaggtaaaaagggaaacactgattatgctgacttactcgaaaaatatcgtaga 225 N Q T K D T I T R Y K G K K G N T D Y A D L L E K Y R R 9521 agtgttttgagaattgagaaaatgatctttagagaaatgaacaaggaaggcttatttctccttgtttatggagggaggtag 9601 253 S V L R I E K M I F R E M N K E G L F L L V Y G G R * 1820RF010 1310 ttgaccgtaagaatatcaaagaatgatagagccaagttagagaaaatctacggtaaatctaacaaagctcgtaaaaaatacaat 1 L T V R I S K N D R A K L E K I Y G K S N K A R K K Y N 1394 cgtttaagacaaaaaggagttgaggaaaggcaacttccaactgttccaacatcaaagaaaagacttattgactacgtaaaatca 29 R L R Q K G V E E R Q L P T V P T S K K R L I D Y V K S 1478 acaaatatgagtcgtagtgattttaacaagatgttagacgagttggtagattttgcacaaccttacaacgagaattamatttft 57 T N M S R S D F N K M L D E L V D F A Q P Y E ENY I F 1562 gagatcaacaagcgaaatgttgcaatctcaagagcgcaaatcaaagaagcgcaaattaaaacagagcaagctcaaaaagcgaaa 85 E I N K R N V A I S R A Q I K E A Q I K T E Q A Q K A K 1646 gaagaacactacaaagagcttaacaaagttgaagttaagaagcccacagaaaacacaattgtcacaccaactattttaacagag 113 E E H Y K E L N K V E V K K P T E N T I V T P T I L T E 1730 ttaggtgctgacttaccttttcaagcaataccagattttaatattgacgctttcacttctccagaaggagttcagtcttattta WO 00/32825 PCT/IB99/02040 322 141 L G A D L P F Q A I P D F N I D A F T S P E G V Q S Y L 1814 gaaaatataggaaaacaagacgaacaatattttgacgaaagagaccaactttattacgacaatttcagacaagcgatgtttact 169 E N I G K Q D E Q Y F D E R D Q L Y Y D N F R Q A M F T 1898 attttcaattcagacgctgacgatattgttcgtttacttgactcaatggggcttgatctatttatgaaaacatatgttagtaac 197 I F N S D A D D I V R L L D S M G L D L F M K T Y V S N 1982 ttcttagacatgaaccttgactacatttatgacgaagcagaagtacaacagaaaaaagaacaagtttacagtaagattgcaaaa 225 F L D M N L D Y I Y D E A E V Q Q K K E Q V Y S K I A K 2066 gtgatcgagtctgaaacaggtggagaagtcccctcatataaccccacgaagaacatcacaattaattcagaaacaggagaagaa 253 V I E S E T G G E V P S Y N P T K N I T I N S E T G E E 2150 ttatga 2155 281 L * 1820RF011 9607 atggtagattttaaccccgacaagcggtttgacggtttacccgctgtattcaaagaacgctttagcaaatatcctcatactgaa 1 M V D F N P D K R F D G L P A V F K E R F S K Y P H T E 9691 tacagatatgaattactattagatgaagaagtatcggctttaattgcctatctgaatgaagttggtgctttagttaatgatatg 29 Y R Y E L L L D E E V S A L I A Y L N E V G A L V N D M 9775 agtggttatttaaattactttatcgaacattttgttgagaagttagaagagatcacaaatgacacactcaaaaaatggttgtct 57 S G Y L N Y F I E H F V E K L E E I T N D T L K K W L S 9859 gatggtacgttagaaaatttaatcaatgatactgtttttgcaaattatatcaaagaaatcaaaagattacaaatcttggttgct 85 D G T L E N L I N D T V F A N Y I K E I K R L Q I L V A 9943 gaaacacgtgctaacagtgtgaatattcttttgacaaaaaataaaccggatgttgctgatgatcgaacattttggtataagatt 113 E T R A N S V N I L L T K N K P D V A D D R T F W Y K I 10027 caacgcgacaatactgattatggagccgatcctattgacacgttacgtattgttgcaatcaataaagttagtggtggaatacc 141 Q R D N T D Y G A D P I D T L R I V A I N K V S G W N T 10111 gctacaggagatatttatcttaacattaaaggaacggagggtgtataa 10158 169 A T G D I Y L N I K G T E G V * 1820RF012 10872 atggcaaataaaaatattcaaatgaaggatagcaatgacaataatttatatccaagtgttcgagcagaaaacttgttagatttg 1 M A N K N I Q M K D S N D N N L Y P S V R A E N L L D L 10956 accagtcgtgctgaattaacaatgacaaattgtcaattatatgcagctggtgataaaacaaatgcaatctcttatctcggtgca 29 T S R A E L T M T N C Q L Y A A G D K T N A I S Y L G A 11040 gtaggtatgctcgaaggtatgataaagtttactgaaagtttgacaaaccctgtgatcacaacgctaccagaaggttttagacca 57 V G M L E G M I K F T E S L T N P V I T T L P E G F R P 11124 ataagaacaaaacgtattggttgtttcgcaaaatattacacaccaaatccaacagatacaaaagaaatggtttatgtatcaatc 85 I R T K R I G C F A K Y Y T P N P T D T K E M V Y V S I 11208 acacctgatggcaaagtaactgtaaatgacaatgtaggtaaaatcgaatatctatccctagataattgcgttttccctctaaaa 113 T P D G K V T V N D N V G K I E Y L S L D N C V F P L K 11292 taa 11294 141 * 1820RF013 10456 atggcagataaaaatattcaaatgcaggataaagatcataatcgtttaatgcctgttacaattgctaaaaatgttctaacaggc 1 M A D K N I Q M Q D K D H N R L M P V T I A K N V L T G 10540 gactctaatcttgaattagttaatgctgaaataagaggtaacgctagtgaagctaaaacacttgcacaacaagctaaagaaact 29 D S N L E L V N A E I R G N A S E A K T L A Q Q A K E T 10624 gctgctggtttgtcaacagaaattgacacagtaacatcaaccgcaaatcaagcgttgacgaaggctggtacagcacaacaaacc 57 A A G L S T E I D T V T S T A N Q A L T K A G T A Q Q T 10708 gcagaacaagcgaaaacaacagcaaacagtatcagcgcagttgcaacggcagctaaaaacacagctgattcagcacaaaaaagt 85 A E Q A K T T A N S I S A V A T A A K N T A D S A Q K S 10792 gcaactgatctagctgttcgagtaagcagtttagaggacacagcaatacaatatactgtattaccatag 10860 113 A T D L A V R V S S L E D T A I Q Y T V L P * 1820RF014 13716 atgatagaatatatcacacaatggttggcagatgataatcatcttgtttatggtttgattatatggttaatggttgcaatgatt 1 M I E Y I T Q W L A D D N H L V Y G L I I W L M V A M I 13800 atcgattttgtgttaggttttacaattgccaaatttaacaaggaaatcgactttagtagttttaaagctaaagcaggtatcatt 29 I D F V L G F T I A K F N K E I D F S S F K A K A G I I 13884 gttaaggtggcagaaatggttttagtggtttactttattcctgtagcagtaaaattcggtgcagtaggtattacaatgtatata 57 V K V A E M V L V V Y F I P V A V K F G A V G I T M Y I 13968 acaatgttggttggtttgattttatcagaaatttatagtatactaggacatatttcagatatcgatgatgataataattggact 85 T M L V G L I L S E I Y S I L G H I S D I D D D N N W T 14052 gattatgttaagaagtttttagacggaacactcaacagaaaggacgatattaaatga 14108 113 D Y V K K F L D G T L N R K D D I K * 182ORF015 854 atggaaatcgtaaaaagcacatttgacacacaaacaccagaaggaatgttacaagtattcaatgccacaaacggggcttcaatt 1 M E I V K S T F D T Q T P E G M L Q V F N A T N G A S I 938 ccgttacgtaacgcaattggcgaagtactagaattgaaagatattctagtttactcagacgaagtttctggttttggtggagcc 29 P L R N A I G E V L E L K D I L V Y S D E V S G F G G A 1022 gaaccatcacaagcagaactagtcgctttcttcacagaagatggtaaaacttatgcgggtgtatcagcagtagcaacaaaatca 57 E P S Q A E L V A F F T E D G K T Y A G V S A V A T K S 1106 gctaaaaacctaattgatatgatgactgctaaccctgacatcaaaccaaaaatttcttttgtcgaaggaaaatcaaacggtgg 85 A K N L I D M M T A N P D I K P K I S F V E G-KS N -eC 1190 caaaaatttgtaaatctacaagtggtttcactgtag 1225 113 Q K F V N L Q V V S L * 1820RF016 17033 atgattaacaatttatcattaattttagagggtttaaatcaactaactaaagatgacaacgatagtttagcgtctatcaagtca 1 M I N N L S L I L E G L N Q L T K D D N D S L A S I K S 16949 gaaataacacaaggaggaaaacaattaattttatacattgattacgttacaaaagagttcgtgttaacacatgataaatataac WO 00/32825 PCT/IB99/02040 323 29 E I T Q G G K Q L I L Y I D Y V T K E F V L T H D K Y N 16865 tatgtttatcttgatagccattgcattaatatcgcaataacgaaatcaatgaaaagcgttgaacactatgcggaacaattgaaa 57 Y V Y L D S H C I N I A I T K S M K S V E H Y A E Q L K 16781 catgacggatataaacaaattacggacaaatag 16749 85 H D G Y K Q I T D K * 1820RF017 154 atgaaatattcactacaacaaatagatgaaattaaatcaacaattttcagaattagattaaaaaggcatgaactagaggaattg 1 M K Y S L Q Q I D E I K S T I F R I R L K R H E L E E L 238 gtggacgaagtaaacgatattgctaaagatccggaggaaagatatcttttatcgttttattacacagaagaagaacgtttgttt 29 V D E V N D I A K D P E E R Y L L S F Y Y T E E E R L F 322 gaaattccctctgcaagattaatagattattacaacgaaaagatcacaaatctgaaatcggaaatcatatcactcgaaaaaaga 57 E I P S A R L I D Y Y N E K I T N L K S E I I S L E K R 406 ttacaaaaactagtaaaataa 426 85 L Q K L V K * 1820RF018 16737 atgattgcacgaacattcaaagaacaccgcgaactaattgaatggttacgtttctactgtaaacgtaacctttcagacaatgaa 1 M I A R T F K E H R E L I E W L R F Y C K R N L S D N E 16653 aaaatagagatcatagaggggactttacaagatttcgacgttccggaaataaatatcaccgaacttttgttaactcattcaacg 29 K I E I I E G T L Q D F D V P E I N I T E L L L T H S T 16569 ctattacccgaatcgagtcaatttaacattcttgaaaagtattgtcaggcaatgaaattagtaacttcatacgtaaaagttggt 57 L L P E S S Q F N I L E K Y C Q A M K L V T S Y V K V G 16485 tctcgctatcagttagcgttacaaataccaaaaggctatttaaaggaggtggaataa 16429 85 S R Y Q L A L Q I P K G Y L K E V E * 1820RF019 4323 atggaaattaaagaacatgaatcaattttaaatggtattcttgaaagtgtcacagacggtgaagcaagatcaaagattgtagaa 1 M E I K E H E S I L N G I L E S V T D G E A R S K I V E 4407 catcttgaagcattgcgagaagactacggagcaacaactgaagctttgacatcagcaaatagcacacttgaaaagttaaagaaa 29 H L E A L R E D Y G A T T E A L T S A N S T L E K L K K 4491 gataacgaagcgttggttatttcaaactcaaaattgttccgagaacgagcgatcgtagaaccagcagaaaataacgaaccagaa 57 D N E A L V I S N S K L F R E R A I V E P A E N N E P E 4575 acagaccagaatattacactagacgatttaggaatttaa 4613 85 T D Q N I T L D D L G I * 1820RF020 10158 atggcagacattagaacacaactaacaagtgaagatggatcagacaatttatttccaatttcaaaagccgttaatattatgact 1 M A D I R T Q L T S E D G S D N L F P I S K A V N I M T 10242 aatagcggtacgaatgtagaaggagaattgggtacactcaaacaaaatgacgaaacaatgaatacctcagttcaaaatgctgta 29 N S G T N V E G E L G T L K Q N D E T M N T S V Q N A V 10326 gttactgccaatcaagcaaaagattctgtagctgaattaaatgtaaatgttggtaaactaaccaatcgaataacaacattagag 57 V T A N Q A K D S V A E L N V N V G K L T N R I T T L E 10410 agtacagtggctaatcttgatggtattcgttatgtagaggtgtaa 10454 85 S T V A N L D G I R Y V E V * 1820RF021 17339 atgaacaataaatcattaatagctgaaaaaggagaggtatctctacttcacccctttaatgagtgggatatgaattatcatatc 1 M N N K S L I A E K G E V S L L H P F N E W D M N Y H I 17255 atagataccgaaaacaataaacattatcttattgatattgatgaggtaggcgatgaggaatattgtttgttatcttttgaagaa 29 I D T E N N K H Y L I D I D E V G D E E Y C L L S F E E 17171 ctaaaggaattagatatggatcttatttccgagtattcatggaaaactacagaaataacatattaa 17106 57 L K E L D M D L I S E Y S W K T T E I T Y * 1820RF022 12868 gtgggttgtctaatgctaaagctgaaacgttggaaggtcaagcagagatcatcgctcaaggggataaaacaggtcaatggatgg 1 V G C L M L K L K R W K V K Q R S S L K G I K Q V N G W 12952 ataatacacctgtttcttctgcaggttatactaaccctcagaccctttcagcatttaaacaatctgcaaatattgatgttgcta 29 I I H L F L L Q V I L T L R P F Q H L N N L Q I L M L L 13036 caattaattttatgtgtcactgggaacgccctggtaaacttcatatcgaagaaagacttgatcttgcacaagcttatagtaagc 57 Q L I L C V T G N A L V N F I S K K D L I L H K L I V S 13120 atattgacggtagcggtggcggtggcgtaa 13149 85 I L T V A V A V A * 1820RF023 12189 atggttgttgttttggacatgcaagttatgcgcatatcctcgataataacttacgccaccttcgattgtgttaccagaaatttc 1 M V V V L D M Q V M R I S S I I T Y A T F D C V T R N F 12105 acagaaattaattacattctgataatcatcgtcattgtcgataatgatcgctgtacaaaaatgaatacggttgtttttcacaaa 29 T E I N Y I L I I I V I V D N D R C T K M N T V V F H K 12021 gaaacctctaaaacctgtacccctagtattgatatcgttcccttgccacataccatttacatcgggaaaagctgttttgataat 57 E T S K T C T P S I D I V P L P H T I Y I G K S C F D N 11937 tgcttgagagatattagagaatag 11914 85 C L R D I R E 1820RF024 6174 atgcttgtaactatctcatctttaaaaacgaagaaacttatcctagtaaatggcagtatgcctttgttactgatattgaata ta 1 M L V T I S S L K T K K L I L V N G S M P L L-L I_-L-N I 6258 agaatgacaacacaagtttcgttacctttgaaattgatgttttacaaacttatcgtttcgatattggtatacgagaaagtttca 29 R M T T Q V S L P L K L M F Y K L I V S I L V Y E K V S 6342 ttgcaaaagaacaccctcaactttattattcgaatggaatacctttcattaatacaattgaagagtcgcttgattacggtagag 57 L Q K N T L N F I I R M E Y L S L I Q L K S R L I T V E 6426 aatacacaacaacaaatgtaa 6446 85 N T Q Q Q M * WO 00/32825 PCT/IB99/02040 324 1820RF025 548 atgggtcgaaaactaatgcaacgaaacgtaacatcaactaaagtagaattctcagaagttatcgtacaagatggagcgccaaca 1 M G R K L M Q R N V T S T K V E F S E V I V Q D G A P T 632 attgtaccatgcgaaccagttgtcttaacaggaaaactttcagaagaaaaagctttatcagcgatcaaacgtaaaaaccctgat 29 I V P C E P V V L T G K L S E E K A L S A I K R K N P D 716 aaaaacgtagttgtaacaaatgtttcacatgaaacagcgctttacacaatgccagtcgataaatttatcgagttagcagacaaa 57 K N V V V T N V S H E T A L Y T M P V D K F I E L A D K 800 tcaacacaagcctaa 814 85 S T Q A * 1820RF026 13259 atggaaattatttggtctgccgtttcctgcatgcgtgccaaaaagttgtccactcatgaaacttttaggatcaagatttgtatt 1 M E I I W S A V S C M R A K K L S T H E T F R I K I C I 13175 cttgattggggttccatagcaacgttttacgccaccgccaccgctaccgtcaatatgcttactataagcttgtgcaagatcaag 29 L D W G S I A T F Y A T A T A T V N M L T I S L C K I K 13091 tctttcttcgatatgaagtttaccagggcgttcccagtgacacataaaattaattgtagcaacatcaatatttgcagattgttt 57 S F F D M K F T R A F P V T H K I N C S N I N I C R L F 13007 aaatgctga 12999 85 K C * 182ORF027 14896 atgaacatgattgtatgttcctctaatatgatcgagttgtgttggatcagacaattcaaagatcgtttctccgtcaaaataaaa 1 M N M I V C S S N M I E L C W I R Q F K D R F S V K I K 14812 cacgcttgtgctacctgttgtaagagtgaaaataaactcatcacttgtggcgtcaaatattttattttcaggaggaacaatttg 29 H A C A T C C K S E N K L I T C G V K Y F I F R R N N L 14728 atcctgttttttacctacatacagatcccatgtattaccatcgccatagaaaacattcaaatcaagattgccgttgtatcctgg 57 I L F F T Y I Q I P C I T I A I E N I Q I K I A V V S W 14644 taa 14642 85 * 1820RF028 14430 atgtttataataaaacaggcgttaaagcatggttttatacgtatacagcaaacctcaatacaactgatttttctagtattgcaa 1 M F I I K Q A L K H G F I R I Q Q T S I Q L I F L V L Q 14514 aaggcgattatggtttatgggttgctgaatatggatcaaatcaaccacaaggctactctcaaccagcgccacctaaaacaaata 29 K A I M V Y G L L N M D Q I N H K A T L N Q R H L K Q I 14598 attttccaattgttgcctgttttcagtttacaagtaaaggacgtttaccaggatacaacggcaatcttgatttga 14672 57 I F Q L L P V F S L Q V K D V Y Q D T T A I L I * 1820RF029 17606 atgaatgaaccgatcgtatacacagaaatttattcaaataacgtggtatgtatgaaaatttttagagatgaggataaacttagt 1 M N E P I V Y T E I Y S N N V V C M K I F R D E D K L S 17522 aaattcctctatttagaatttgaggtggatgaggctaaaaagttacttgaaaataaaacaatttcatttgatgataactggact 29 K F L Y L E F E V D E A K K L L E N K T I S F D D N W T 17438 ttctcaataaattatccagaatattaa 17412 57 F S I N Y P E Y * 1820RF030 16429 atggctacattctacaaggaaccaatatacgatatcacagtattttatatagatggttgggaggttttgatacacaaaaccgaa 1 M A T F Y K E P I Y D I T V F Y I D G W E V L I H K T E 16345 cctctcaccttaacaaaagcattaaaatatagccgtatatacctagaaatggatatagtgaattgcgttagaatagaaagaaat 29 P L T L T K A L K Y S R I Y L E M D I V N C V R I E R N 16261 ggacgtcctatagctacattttacagggaattattaaaactgtataaggagaaagaactatga 16199 57 G R P I A T F Y R E L L K L Y K E K E L * 1820RF031 8603 atgttacctgaactttcaatctgttcattgttagataagacttctgatgtttgtacacgtgcagtcttatctacgttagcattg 1 M L P E L S I C S L L D K T S D V C T R A V L S T L A L 8519 ttgatacctagaaaagttaacacttcattccatacttcgttcaattctgatcgtagtttatctactacatatggagcatttgtt 29 L I P R K V N T S F H T S F N S D R S L S T T Y G A F V 8435 tgccatacattaaaagattcgtcaaactccatatctttatccacaaaaacagcctga 8379 57 C H T L K D S S N S I S L S T K T A * 1820RF032 11413 atgtttcatcaaaaacaacttgtttcgggttcgtttcagggtgcaataggtaattcttttgattttcttctttcatcttgttca 1 M F H Q K Q L V S G S F Q G A I G N S F D F L L S S C S 11329 tttgaatatcaattcgttcttccatatgaacctccttattttagagggaaaacgcaattatctagggatagatattcgatttta 29 F E Y Q F V L P Y E P P Y F R G K T Q L S R D R Y S I L 11245 cctacattgtcatttacagttactttgccatcaggtgtgattgatacataa 11195 57 P T L S F T V T L P S G V I D T * 1820RF033 4942 atgtcaacaaaaatttcttcaatcgttcgacctaaaggcatgtttccttttttaaacattttcaaagggttacgccaagatttg 1 M S T K I S S I V R P K G M F P F L N I F K G L R Q D L 4858 tatcggataactactttaccaatacggtcaactaaagttgaaataaattcgttttttactacgtctaaacgtgtgatccctgca 29 Y R I T T L P I R S T K V E I N S F F T T S K R V I P A 4774 ccaaccgcttcgatgttatctgcatttggcataggtacgttcgcctga 4727 57 P T A S M L S A F G I G T F A * 1820RF034 6160 gtgtttatctactctaaaaactcccccgagttgtgtatccctttgataagaacaatctctattctcgttaagaacaggaaacga 1 V F I Y S K N S P E L C I P L I R T I S I L V K N R K R 6076 attaaagtacgattcctgttcctgttgagttttaaaccatcttgtgtgtgtataggtgttatcaaaaggcacgttagccaacaa 29 I K V R F L F L L S F K P S C V C I G V I K R H V S Q Q 5992 ttttacatttgtataccttcttgccataattgtcctccttag 5951 WO 00/32825 PCT/IB99/02040 325 57 F Y I C I P S C H N C PP * 1820RF035 15758 atggcgcataagaaactactatttttacttctcttttcaataaacgtatcactatcattgacaaactcattgttgatactaaaa 1 M A H K K L L F L L L F S I N V S L S L T N S L L I L K 15674 tcttcgtattctgttccacgaatcaatctaccaaaaggtgtttctctcttcacttctgcaaagtcttttgaatcacacaattca 29 S S Y S V P R I N L P K G V S L F T S A K S F E S H N S 15590 atcaatatacctcgatcttga 15570 57 I N I P R S * 1820RF036 2315 atgtctgtgctgccttgcattttacaccactcaaaaaaagaatcgatttctaaaccgaacgtcatattgtcaacgttgtctata 1 M S V L P C I L H H S K K E S I S K P N V I L S T L S I 2231 tcgcatacgccccacgaccatacacgacaatcgttgagatcagttgttgtttcaaagtcgccagtatatttcttaatcataatt 29 S H T P H D H T R Q S L R S V V V S K S P V Y F L I I I 2147 cttctcctgtttctgaattaa 2127 57 L L L F L N * 1820RF037 12280 gtgagttacgacaataaacatctacatcaatataagcttgatccacatcttgaaactcaaacaaagcgtttctatttccgtatg 1 V S Y D N K H L H Q Y K L D P H L E T Q T K R F Y F R M 12196 ctagaaaatggttgttgttttggacatgcaagttatgcgcatatcctcgataataacttacgccaccttcgattgtgttaccag 29 L E N G C C F G H A S Y A H I L D N N L R H L R L C Y Q 12112 aaatttcacagaaattaa 12095 57 K F H R N * 1820RF038 14769 gtgatgagtttattttcactcttacaacaggtagcacaagcgtgttttattttgacggagaaacgatctttgaattgtctgatc 1 V M S L F S L L Q Q V A Q A C F I L T E K R S L N C L I 14853 caacacaactcgatcatattagaggaacatacaatcatgttcatggaaaagaaatcccatcaatggtgtggacacctgaacaat 29 Q H N S I I L E E H T I M F M E K K S H Q W C G H L N N 14937 ttgatatttacttaa 14951 57 L I F T * 1820RF039 9992 atgttgctgatgatcgaacattttggtataagattcaacgcgacaatactgattatggagccgatcctattgacacgttacgta 1 M L L M I E H F G I R F N A T I L I M E P I L L T R Y V 10076 ttgttgcaatcaataaagttagtggctggaataccgctacaggagatatttatcttaacattaaaggaacggagggtgtataat 29 L L Q S I K L V A G I P L Q E I F I L T L K E R R V Y N 10160 ggcagacattag 10171 57 G R H * 1820RF040 16202 atgagaaaagatttcgtctacattaacacacccgatccaaaagcaaacaaaaaggcgttagcaaaaatcactaacgccaaagaa 1 M R K D F V Y I N T P D P K A N K K A L A K I T N A K E 16118 ccaaaacaaaactatcgcagactacaattactatgttatctactattcatcattgtaatagaactaatcgtggtagctctacta 29 P K Q N Y R R L Q L L C Y L L F I I V I E L I V V A L L 16034 aaatag 16029 57 K * 1820RF041 3886 atggaactatataaagcaatgtttatcgtacgtgatgaaggtactattgacggttacgatactgaacactatgtagatatttct 1 M E L Y K A M F I V R D E G T I D G Y D T E H Y V D I S 3970 ttacatgactttgaagaaatatatggaaaagaaacacgtgaaattgaagcagtaacattagtaaaaacaggaaatttaaaaaaa 29 L H D F E E I Y G K E T R E I E A V T L V K T G N L K K 4054 taa 4056 57 * 1820RF042 10832 gtgtcctctaaactgcttactcgaacagctagatcagttgcacttttttgtgctgaatcagctgtgtttttagctgccgttgca 1 V S S K L L T R T A R S V A L F C A E S A V F L A A V A 10748 actgcgctgatactgtttgctgttgttttcgcttgttctgcggtttgttgtgctgtaccagccttcgtcaacgcttga 10671 29 T A L I L F A V V F A C S A V C C A V P A F V N A * 1820RF043 10652 gtgtcaatttctgttgacaaaccagcagcagtttctttagcttgttgtgcaagtgttttagcttcactagcgttacctcttatt 1 V S I S V D K P A A V S L A C C A S V L A S L A L P L I 10568 tcagcattaactaattcaagattagagtcgcctgttagaacatttttagcaattgtaacaggcattaaacgattatga 10491 29 S A L T N S R L E S P V R T F L A I V T G I K R L * 1820RF044 6457 atgaaaagttgttacatttgttgttgtgtattctctaccgtaatcaagcgactcttcaattgtattaatgaaaggtattccatt 1 M K S C Y I C C C V F S T V I K R L F N C I N E R Y S I 6373 cgaataataaagttgagggtgttcttttgcaatgaaactttctcgtataccaatatcgaaacgataagtttgtaa 6299 29 R I I K L R V F F C N E T F S Y T N I E T I S L * 1820RF045 6729 atgaatggtatacctgtatacgacgttacatacatcccgactatcttatttaaaaaaggttctttcgttgtaagaaacgccatg 1 M N G I P V Y D V T Y I P T I L F K K G S F V-V RN T M 6645 tactctccaaaattagcattgcctgccccatttggtttgtatacctccccacttgaattgataggaagtaaataa 6571 29 Y S P K L A L P A P F G L Y T S P L E L I G S K * 1820RF046 2372 atggtttcaaatggtgtaaagaagcaaaagaagatcgaacattctccacactcatatcaaatatgggtcaatggtatgctttgg 1 M V S N G V K K Q K K I E H S P H S Y Q I W V N G M L W 2456 aaatttgttgggaagttaattacacaacaacaaaatcaggtaaaacgaaaaaagagaaatctcgaacaataa 2527 29 K F V G K L I T Q Q Q N Q V K R K K R N L E Q * WO 00/32825 PCT/IB99/02040 326 1820RF047 13353 atgctcccattgttccaacatgtgttactgttccatcgcaacatgcaatcatttcattgccagggtgatcaattgaaccaaagt 1 M L P L F Q H V L L F H R N M Q S F H C Q G D Q L N Q S 13269 ccaaaccatcatggaaattatttggtctgccgtttcctgcatgcgtgccaaaaagttgtccactcatga 13201 29 P N H H G N Y L V C R F L H A C Q K V V H S * 1820RF048 3395 atgtcagggtttgttccgaactttccatacaagctatttaacatacctttggcgttagcttttctagccccttcggtggtgttc 1 M S G F V P N F P Y K L F N I P L A L A F L A P S V V F 3311 tttacttcgatccatttatcgatccagcctttgaacatatcacaagaagctttgaacatatatccgtaa 3243 29 F T S I H L S I Q P L N I S Q E A L N I Y P * 1820RF049 1578 atgttgcaatctcaagagcgcaaatcaaagaagcgcaaattaaaacagagcaagctcaaaaagcgaaagaagaacactacaaag 1 M L Q S Q E R K S K K R K L K Q S K L K K R K K N T T K 1662 agcttaacaaagttgaagttaagaagcccacagaaaacacaattgtcacaccaactattttaa 1724 29 S L T K L K L R S P Q K T Q L S H Q L F * 1820RF050 8012 atggttatcttggtttctttaaagaccctacacttgggttcatggtttgcgcaggggcagaagatggtcaaatcgatcattatc 1 M V I L V S L K T L H L G S W F A Q G Q K M V K S I I I 8096 acaaccctattttctttacagcaaacgaagcaatgtatcacaagagatatcctgttttaa 8155 29 T T L F S L Q Q T K Q C I T R D I L F * 1820RF051 9390 atgcttctgaaaaagaaacaaagaacacagacattaataaagatcaaaatcaaaccaaagatacgattacacgatataaaggta 1 M L L K K K Q R T Q T L I K I K I K P K I R L H D I K V 9474 aaaagggaaacactgattatgctgacttactcgaaaaatatcgtagaagtgttttga 9530 29 K R E T L I M L T Y S K N I V E V F * 182ORF052 4096 gtgatagttgacaagagtcaaatttggcgagattgggcgaatgtacacgtgaaatatcgtgcgctcccgttaagttatggacac 1 V I V D K S Q I W R D W A N V H V K Y R A L P L S Y G H 4180 ataaacgttttgaccgtcaaccaatcgcaaaaaccttttaggagtagcccttaa 4233 29 I N V L T V N Q S Q K P F R S S P * 1820RF053 15656 gtggaacagaatacgaagattttagtatcaacaatgagtttgtcaatgatagtgatacgtttattgaaaagagaagtaaaaata 1 V E Q N T K I L V S T M S L S M I V I R L L K R E V K I 15740 gtagtttcttatgcgccattgcttttgaagggaaaatctttgggtattggatag 15793 29 V V S Y A P L L L K G K S L G I G * 1820RF054 8136 gtgatacattgcttcgtttgctgtaaagaaaatagggttgtgataatgatcgatttgaccatcttctgcccctgcgcaaaccat 1 V I H C F V C C K E N R V V I M I D L T I F C P C A N H 8052 gaacccaagtgtagggtctttaaagaaaccaagataaccattagtgtgtaa 8002 29 E P K C R V F K E T K I T I S V * 1820RF055 8324 atgaaaagaaatacttctcattgctacaagcttataaccaaattgacgaaaataatcaggctgtttttgtggataaagatatgg 1 M K R N T S H C Y K L I T K L T K I I R L F L W I K I W 8408 agtttgacgaatcttttaatgtatggcaaacaaatgctccatatgtag 8455 29 S L T N L L M Y G K Q M L H M * 1820RF056 6549 gtggcccatctcctttttcctattatttacttcctatcaattcaagtggggaggtatacaaaccaaatggggcaggcaatgcta 1 V A H L L F P I I Y F L S I Q V G R Y T N Q M G Q A M L 6633 attttggagagtacatggcgtttcttacaacgaaagaaccttttttaa 6680 29 I L E S T W R F L Q R K N L F * 1820RF057 8264 atgtccgccatatctaaagcaaaacgatgtaaacttggtaacgtaggaactttcaagtcattattatacaacatgatacatttt 1 M S A I S K A K R C K L G N V G T F K S L L Y N M I H F 8180 gatttatcatcatcatcatcatatcttaaaacaggatatctcttgtga 8133 29 D L S S S S S Y L K T G Y L L * 1820RF058 5176 gtgtattcaaattcgcttacttcgtcacctgtgtataaagcgttcattacaccagcaacgaaactattgaaattatcccatgaa 1 V Y S N S L T S S P V Y K A F I T P A T K L L K L S H E 5092 gtaaatgctttttctaaccatgcttcttggatcgtttgtttgtag 5048 29 V N A F S N H A S W I V C L * 1820RF059 15876 atggtctttcgtagtcattgcataaaaatgatttgtatttggttgataatcataactcacatagacacaacctgtttcagcgtc 1 M V F R S H C I K M I C I W L I I I T H I D T T C F S V 15792 tatccaatacccaaagattttcccttcaaaagcaatggcgcataa 15748 29 Y P I P K D F P F K S N G A * 1820RF060 15404 gtgatttttgatttctcaattaaaaactcatcaaacaaaattgtacgaacttcgggatattcattagatttttcaattccccac 1 V I F D F S I K N S S N K I V R T S G Y S L D F S I P H 15320 gtactaagtggaacagcccaacccattaatttatcatcacaatag 15276 29 V L S G T A Q P I N L S S Q * 1820RF061 2102 atgaggggacttctccacctgtttcagactgatcacttttgcaatcttactgtaaacttgttcttttttctgttgtacttctg WO 00/32825 PCT/IB99/02040 327 1 M R G L L H L F Q T R S L L Q S Y C K L V L F S V V L L 2018 cttcgtcataaatgtagtcaaggttcatgtctaagaagttactaa 1974 29 L R H K C S Q G S C L R S Y * 1820RF062 1992 atgtctaagaagttactaacatatgttttcataaatagatcaagccccattgagtcaagtaaacgaacaatatcgtcagcgtct 1 M S K K L L T Y V F I N R S S P I E S S K R T I S S A S 1908 gaattgaaaatagtaaacatcgcttgtctgaaattgtcgtaa 1867 29 E L K I V N I A C L K L S * 1820RF063 14306 gtgtaccttctaaacccctctcatgcgcaaaatgatacacaccaatctttttacctaaagacaaagcttgttgaaatgctcggt 1 V Y L L N P S H A Q N D T H Q S F Y L K T K L V E M L G 14222 cacaatcagggtttacataacctgttccgcctgttgctttaa 14181 29 H N Q G L H N L F R L L L * 1820RF064 7356 atgatgttagtcaaaccaacaaaagggttgttacttgctaaggctgaaaagatcgctcctcctgtactcattgcactgtttccc 1 M M L V K P T K G L L L A K A E K I A P P V L I A L F P 7272 ataccatgtctgaaagtattgcgaatgttttgctcttga 7234 29 I P C L K V L R M F CS * 1820RF065 3582 atgaatgctatctgtatcacaataaataatgcgatcaaaacatttttgagcggttgtaatggtagtatatctaccccaagccgt 1 M N A I C I T I N N A I K T F L S G C N G S I S T P S R 3498 cacaaaactagcaagcggaacataaacaggatctcttaa 3460 29 H K T S K R N I N R I S * 1820RF066 4234 atgtggctactcttttttgtgtttcacagaattatgtttcacgtgaaacagtttttatggtataatagaatcaaaaggaggtgg 1 M W L L F F V F H R I M F H V K Q F L W Y N R I K R R W 4318 agattatggaaattaaagaacatgaatcaattttaa 4353 29 R L W K L K N M N Q F * 1820RF067 13882 atgatacctgctttagctttaaaactactaaagtcgatttccttgttaaatttggcaattgtaaaacctaacacaaaatcgata 1 M I P A L A L K L L K S I S L L N L A I V K P N T K S I 13798 atcattgcaaccattaaccatataatcaaaccataa 13763 29 I I A T I N H I I K P * 1820RF068 7267 atgtctgaaagtattgcgaatgttttgctcttgagcaatcaaggagtttttgtttccttgcatgaatgcagaagcatagtcaga 1 M S E S I A N V L L L S N Q G V F V S L H E C R S I V R 7183 tttaactcctacatcgttaggatcattatcgattaa 7148 29 F N S Y I V R I I D 1820RF069 5027 gtggaacaatgtttttacatcgggaacttcctgtttaaatacccctgtaacagactcgtcagggttgaacttatgttcctgtgc 1 V E Q C F Y I G N F L F K Y P C N R L V R V E L M F L C 4943 aatgtcaacaaaaatttcttcaatcgttcgacctaa 4908 29 N V N K N F F N R ST * 182ORF070 1031 gtgatggttcggctccaccaaaaccagaaacttcgtctgagtaaactagaatatctttcaattctagtacttcgccaattgcgt 1 V M V R L H Q N Q K L R L S K L E Y L S I L V L R Q L R 947 tacgtaacggaattgaagccccgtttgtggcattga 912 29 Y V T E L K P R L W H * 1820RF071 11741 atggttttgcattatggttgccacaaggcgctcaaagtggtaaaggaattttctttaatgatactcgcaattacaatcgttttg 1 M V L H Y G C H K A L K V V K E F S L M I L A I T I V L 11825 actttgatttgtttgttcgtaactgtactttaa 11857 29 T L I C L F V T V L * 1820RF072 11723 atgtttacattaaatgccgtcattgtttcaaactttaatgtcgtttctcccgatcctaagaaagtaactacaggtacatcacgt 1 M F T L N A V I V S N F N V V S P D P K K V T T G T S R 11639 ttcaattcaatggtgttagcaaagcgataa 11610 29 F N S M V L A K R * 1820RF073 2876 gtgaagccgcctttgtatgctttacgtaagtctttatcaaaccctaaagacaaaataggaaaccattgtttgaaagttgatttt 1 V K P P L Y A L R K S L S N P K D K I G N H C L K V D F 2792 ccatgtgtagcttttagccaatctttgtaa 2763 29 P C V A F S Q S L * 1820RF074 8923 gtgattgataaattttgtttcaaattctgctcgttttgtttcgtcataaaacggataatcaaaatcaaacaattgttttcggcc 1 V I D K F C F K F C S F C F V I K R I K I K Q L F S A 8839 aacttcaatacgttcttttcgagataa 8813 29 N F N T F F S R * 1820RF075 7463 gtgttacattatctggaatattttcgatatctgccactttacctgccaagaggttcaaaccgttttctttttcagaaacatagt 1 V L H Y L E Y F R Y L P L Y L P R G S N R F L F Q K H S 7379 tgtttacttgttgtcctgctcccatga 7353 29 C L L V V L L P * 1820RF076 2426 atgagtgtggagaatgttcgatcttcttttgcttctttacaccatttgaaaccatttttgaataaccatgaaagcataaactct WO 00/32825 PCT/IB99/02040 328 1 M S V E N V R S S F A S L H H L K P F L N N H E S I N S 2342 ccgtcaaatttttcgttgtggaaataa 2316 29 P S N F S L W K * 1820RF077 11858 atgaaggaacgtatgttgttgttgctagaggtagaggggttacatttgaaaattgtctattctctaatatctctcaagcaatta 1 M K E R M L L L L E V E G L H L K I V Y S L I S L K Q L 11942 tcaaaacagcttttcccgatgtaa 11965 29 S K Q L F P M * 1820RF078 7671 gtgcctacaatatttggttcttttaatttaatgaaattccatgcttttcttgtttgtaagtttggtgtagctactcgattgctc 1 V P T I F G S F N L M K F H A F L V C K F G V A T R L L 7587 tttgtgccatacattgagaagtaa 7564 29 F V P Y I E K * 182ORF079 7488 gtgaaagataagtttgatccaagctgtgttacattatctggaatattttcgatatctgccactttacctgccaagaggttcaaa 1 V K D K F D P S C V T L S G I F S I S A T L P A K R F K 7404 ccgttttctttttcagaaacatag 7381 29 P F S F S E T * 1820RF080 4473 gtgtgctatttgctgatgtcaaagcttcagttgttgctccgtagtcttctcgcaatgcttcaagatgttctacaatctttgatc 1 V C Y L L M S K L Q L L L R S L L A M L Q D V L Q S L I 4389 ttgcttcaccgtctgtga 4372 29 L L H R L * WO 00/32825 PCT/IB99/02040 Table 24 Sequence similarities phage 182 and public databases Phage: 182 Database: nr Query= sid110156|lan|182ORF001 Phage 182 ORF15966-778012 (604 letters) gil138124|spIP07534|VG9_BPPZA TAIL PROTEIN (LATE PROTEIN GP9) >... 384 e-105 gil138l231spIP04331|VG9_BPPH2 TAIL PROTEIN (LATE PROTEIN GP9) >... 374 e-103 gil1429238|gnlIPIDje1173412 (X99260) tail protein (Bacteriophag... 346 3e-94 gil215339 (M12456) p9 tail protein [Bacteriophage phi-29] >gil2... 208 8e-53 gil1181970|gnlIPID~e221269 (Z47794) tail protein [Bacteriophage... 62 8e-09 gil1181968|gnl|PID~e22l267 (Z47794) tail protein (Bacteriophage... 56 6e-07 giI25000301spjQ59968CARASULSO CARBAMOYL-PHOSPHATE SYNTHASE SM3... 49 8e-05 Query= sid1ll0l57Ilan~l82ORFOO2 Phage 182 ORF12152-387311 (573 letters) giJll88481spIPl9894IDPOL_BPM2 DNA POLYMERASE >gi1768961pir1 IJQO ... 665 0.0 gi1l4292301gnl1PID1ell73404 (X99260) DNA polymerase [Bacterioph. ... 657 0.0 gi1ll8849IspIPO368OIDPOLBPPH2 DNA POLYMERASE (EARLY PROTEIN GP ... 654 0.0 gi1ll885l1sp1PO69SOIDPOLBPPZA DNA POLYMERASE (EARLY PROTEIN GP ... 654 0.0 gi115732 (X53371) DNA polymerase (AA 1-575) [Bacteriophage phi-29] 651 0.0 giJ15734 (X53370) DNA polymerase (AA 1-575) (Bacteriophage phi-29] 651 0.0 gi1l5724791gnl1PID1e24230l (X96987) DNA polymerase [Bacteriopha. ... 565 e-160 gil10726561pir1 1S51275 DNA polymerase - phage CP-l >gi18365931g. ... 301 le-80 giIl88471spjP22374IDPOMASCIM PROBABLE DNA POLYMERASE >gi18385. . . 71 3e-1 gi146l9621sp1P33537IDPOMNEUCR PROBABLE DNA POLYMERASE >gil2833..3. 65 le-09 gi14619631sp1P33538jDPOM_ NEUIN PROBABLE DNA POLYMERASE >giIl8 ... 62 le-08 gilloB44871pirlI 41618 DNA polymerase - slime mold (Physarum po ... 61 3e-08 giJ2435429 (AF012250) unassigned reading frame (possible DNA po .. . 61 3e-08 gij578lS71gnl1PID~e246743 (X52106) DNA polymerase (Neurospora i. ... 59 le-07 gil21479691pir1 1872369 probable DNA-polymerase - Gelasinospora ... 58 2e-07 gi2l47968pirlQ5S62752 probable DNA-polymerase - Gelasinospora ... 58 2e-07 gi3511140 (AF061244) B type DNA polymerase (Agrocybe aegerita 57 3e-07 gilll8849|spIP10479DPOLBPPRD DNA POLYMERASE (PROTEIN P1) gi ... 56 6e-07 gi578144 (X63909) putative DNA-polymerase, B-type [Morchella c... 47 3e-04 gi232013sp|P30322IDPOM_AGAST PROBABLE DNA POLYMERASE >gi3208... 46 6e-04 Query= sid1ll0ls91lanll82ORFOO4 Phage 182 ORF14626-595413 (442 letters) gil138967sp|P3849VG8NBPPH2 MAJOR HEAD PROTEIN (LATE PROTEIN ... 309 2e-83 gill3818spIP0753OVG8_BPPZA MAJOR HEAD PROTEIN (LATE PROTEIN ... 305 3e-82 gill4292361gnl12PDel73410 X99260) major head protein Bacter ... 300 le-80 gi1l5819581gnlPID1e22257 (47794) major head protein (Bacteri ... 152 6e-36 Query= sid1ll0l6O1lanll82ORFOOS Phage 182 ORF112651-1370013 (349 letters) gi1137932spIP1532VO3_BPPH2 MORPHOGENESIS PROTEIN 1 (LATE PR... 52 8e-06 gi1l4292421gnl1PD1e 7346 (X99260) morphogenesis protein Bac... 48 7e-05 gill37933|spIP07538VG3_BPP A MORPHOGENESIS PROTEIN 1 (LATE PR ... 47 2e-04 Query= sid1l10196lan|182ORF006 Phage 182 ORF114995-1602611 (343 letters) gil137944|sp|P130149VG6_BPPH2 ENCAPSIDATION PROTEIN (LATE PROT ... 402 e-13 giI379451spIP07541|VG86_BPPZA ENCAPSIDATION PROTEIN (LATE PROT ... 402 e-12 gil14292451gnl1PIDje1173419 (X99260) encapsidation protein [Bacr... 381 e-105 giJl1181972gnlIPID~e221271 (Z47794) encapsidation protein (Bact ... 159 2e-38 Query= sid|110162lanl182ORF007 Phage 182 ORF17795-877511 (326 letters) WO 00/32825 PCT/IB99/02040 330 gil1429239|gnlIPIDjel173413 (X99260) upper collar protein (Bact... 271 5e-72 gil137915|spIP07535|VG10_BPPZA UPPER COLLAR PROTEIN (CONNECTOR ... 256 le-67 gi|137914|splP04332|VG10_BPPH2 UPPER COLLAR PROTEIN (CONNECTOR ... 256 2e-67 gil1181960|gnllPIDje221259 (Z47794) connector protein [Bacterio... 148 6e-35 Query= sid|110163|lanh182ORF008 Phage 182 ORF114105-1498312 (292 letters) gil42l0750jgnl1PIDje1374037 (AJ132604) LysL protein [Lactococcu ... 139 2e-32 gij462559|spIP34020ILYCCLOAB AUTOLYTIC LYSOZYME (1,4-BETA-N-AC... 75 8e-13 gil2327014 (U82823) putative lysozyme (Saccharopolyspora erythr... 64 2e-09 gil1266521sp|P25310jLYCMSTRGL LYSOZYME Ml PRECURSOR (1,4-BETA-... 60 2e-08 gill27789|spIP19386|LYCABPCP9 LYSOZYME (ENDOLYSIN) (MURAMIDASE... 60 2e-08 gil67761|pir|IMUBPCP N-acetylmuramoyl-L-alanine amidase (EC 3.5... 59 3e-08 gil4105636 (AF049087) lys [Leuconostoc oenos bacteriophage 10MC 59 3e-08 gij623084 (L02496) muramidase; muramidase [Bacteriophage LL-Hj 57 le-07 gil127787|spIP15057ILYCABPCP1 LYSOZYME (ENDOLYSIN) (MURAMIDASE... 57 2e-07 gil126597|splP00721|LYCHCHASP N,O-DIACETYLMURAMIDASE (LYSOZYME... 57 2e-07 gil127788IspjP19385ILYCABPCP7 LYSOZYME (ENDOLYSIN) (MURAMIDASE ... 57 2e-07 gil67762|pir|IMUBPC7 N-acetylmuramoyl-L-alanine amidase (EC 3.5... 56 3e-07 gil3025168|spIP76421|YEGX ECOLI HYPOTHETICAL 32.0 KD PROTEIN IN... 53 2e-06 giJ4204413 (AF047001) Lys44 [Oenococcus oeni temperate bacterio ... 53 3e-06 gij21169781gnlIPID~d1020940 (D88151) cortical fragment-lytic en... 52 5e-06 gil2392844 (AF011378) lysin [Bacteriophage sk1] 48 8e-05 Query= sid|110164Ilan|182ORF009 Phage 182 ORF18765-960112 (278 letters) giI1429240|gnllPIDjel173414 (X99260) lower collar protein [Bact ... 180 le-44 gill37921|spIP04333|VG11_BPPH2 LOWER COLLAR PROTEIN (LATE PROTE ... 171 Se-42 gil215341 (M12456) p11 lower collar protein [Bacteriophage phi-29] 98 9e-20 gil2241621prfJ|1011232B protein p1l,lower collar [Bacteriophage... 97 le-19 gi1535260 (Z30339) STARP antigen [Plasmodium reichenowi] 50 le-Os giJ4049753 (AF063866) ORF MSV230 hypothetical protein [Melanopl ... 49 4e-05 gil2131557|pir|IS70306 hypothetical protein YEL077c - yeast (Sa... 48 5e-OS gil131782|spjP127531RA50_YEAST DNA REPAIR PROTEIN RAD50 (153 KD ... 48 7e-05 giI2131309|pirj|S70305 hypothetical protein YBL113c - yeast (Sa ... 47 2e-04 gil499325 (Z26314) STARP antigen [Plasmodium falciparum} 46 3e-04 gi|3845171 (AE001391) ribosome releasing factor (00, TP) [Plasm... 46 3e-04 gil731903Isp|P404341YIR7_YEAST HYPOTHETICAL 197.5 KD PROTEIN IN... 45 Se-04 gil1632829|gnlIPIDIe276379 (Y08924) AARP2 protein [Plasmodium f... 45 5e-04 gi|11764901spIP40889|YJW5_YEAST HYPOTHETICAL 197.6 KD PROTEIN I... 45 Se-04 gil10773001pir||S51848 hypothetical protein HRD1054 - yeast (Sa ... 45 Se-04 giJ2425143 (AF020407) WimA [Dictyostelium discoideum) 45 6e-04 gil1181961|gnlIPIDe221260 (Z47794) collar protein [Bacteriopha ... 45 6e-04 gil21326571pir||S64819 probable membrane protein YLL067c - yeas... 45 8e-04 gil2l33041|pir|IS65341 probable membrane protein YPR204w - yeas... 45 8e-04 giJ7302751spIP397931PBPA_BACSU PENICILLIN-BINDING PROTEINS 1A/1. ... 45 8e-04 Query= sidJ101651lanJ1820RF010 Phage 182 ORF11310-215512 (281 letters) gill35604jspIP068l21TERM_-BPNF DNA TERMINAL PROTEIN >gil758151pi. ... 69 3e-11 giJl5724781gnlIPID~e242334 (X96987) terminal protein [Bacteriop. ... 65 3e-10 gijl42923ljgnljPIojell73405 (X99260) terminal protein [Bacterio. ... 64 le-OS Query= sidlll0l66IlanJl82ORF0ll Phage 182 ORF19607-10158Il (183 letters) gill379281spIP075371VGl2_BPPZA PRE-NECK APPENDAGE PROTEIN (LATE ... 51 6e-06 gijl42924ljgnlIPIDjell73415 (X99260) pre-neck appendage protein ... 51 6e-06 giJl379271spIP203451VG12_BPPH2 PRE-NECK APPENDAGE PROTEIN (LATE ... 50 le-OS Query= sidJ1l01691lanJ1820RF0l4 Phage 182 ORF113716-1410813 (130 letters) gi11379361spIP1l881VGl4_BPPH2 LYSIS PROTEIN (LATE PROTEIN GPl4. ... 97 6e-20 gill379381spIP07S391VG14_BPPZA LYSIS PROTEIN (LATE PROTEIN GP14. ... 96 8e-20 giJ14292431gnlIPIole1173417 (X99260) lysis protein [Bacteriopha. ... 96 8e-20 giJ215332 (M14782) lysis protein [Bacteriophage phi-29] 94 5e-19 Query= sidJ110l701lanJ1820RF0l5 Phage 182 ORF1854-122512 (123 letters) WO 00/32825 PCT/IB99/02040 331 gil15670 (V01155) reading frame 10 (may be gene 4) (Bacteriopha ... 70 5e-12 gil1380721sp1P06953jVG5A_BPPZA EARLY PROTEIN GPSA >gil75836|pir... 69 7e-12 Query= sid|110174|1an182ORF019 Phage 182 ORF14323-461313 (96 letters) gil14292351gnlPIDje1173409 (X99260) head morphogenesis protein... 61 2e-09 giI138111|spIP138481VG7_BPPH2 HEAD MORPHOGENESIS PROTEIN (LATE ... 57 3e-08 gil1381121sp|P075331VG7_BPPZA HEAD MORPHOGENESIS PROTEIN (LATE ... 54 le-07 Query= sidJ1101801lan|182ORF025 Phage 182 ORF|548-81412 (88 letters) gil138099|spJP06955IVG6_BPPZA EARLY PROTEIN GP6 >gi|758411pirl I... 55 7e-08 gi11380981spIP03685|VG6_BPPH2 EARLY PROTEIN GP6 >gil75840|pir| |... 54 2e-07 gij1429234|gnlPIDje1173408 (X99260) gene 6 product [Bacterioph ... 54 2e-07 WO 00/32825 PCT/IB99/02040 332 Table 25 Homologies between 182 ORFs and proteins in public databases Phage: 182 Database: Swissprot Query= sid|110156Ilan|182ORF001 Phage 182 ORF15966-778012 (604 letters) gij138124jsplP07534|VG9_BPPZA TAIL PROTEIN (LATE PROTEIN GP9) 384 e-106 gi|138123|spjP0433lVG9_BPPH2 TAIL PROTEIN (LATE PROTEIN GP9) 374 e-103 gil2500030IspIQ59968|CARA_SULSO CARBAMOYL-PHOSPHATE SYNTHASE SM... 49 2e-05 Query= sid|110157|lanh182ORF002 Phage 182 ORF12152-3873|1 (573 letters) gill18848|spIP19894IDPOLBPM2 DNA POLYMERASE 665 0.0 giI1l8849jspjP03680jDPOL_BPPH2 DNA POLYMERASE (EARLY PROTEIN GP2) 654 0.0 gill8851|sp|P06950|DPOL_BPPZA DNA POLYMERASE (EARLY PROTEIN GP2) 654 0.0 gil118847|spIP22374IDPOMASCIM PROBABLE DNA POLYMERASE 71 7e-12 gij4619621sp|P33537|DPOM_NEUCR PROBABLE DNA POLYMERASE 65 3e-10 gi|4619631splP33538DPOM_NEUIN PROBABLE DNA POLYMERASE 62 3e-09 gil118850|splPl0479jDPOLBPPRD DNA POLYMERASE (PROTEIN P1) 56 2e-07 gil2320131spIP30322|DPOMAGABT PROBABLE DNA POLYMERASE 46 2e-04 gil118887|spjP10582IDPOMMAIZE DNA POLYMERASE (S-1 DNA ORF 3) 46 2e-04 Query= sid|110159Flan|182ORF004 Phage 182 ORF14626-5954|3 (442 letters) gijl38117|splPl3849jVG8_BPPH2 MAJOR HEAD PROTEIN (LATE PROTEIN ... 309 6e-84 gij138118|spjP07531|VG8_BPPZA MAJOR HEAD PROTEIN (LATE PROTEIN ... 305 7e-83 Query= sid110160|lanj182ORF005 Phage 182 ORF112651-1370013 (349 letters) gij137932jsp|P15132jVGl3_BPPH2 MORPHOGENESIS PROTEIN 1 (LATE PR... 52 2e-06 gijl37933|spjP07538jVG13_BPPZA MORPHOGENESIS PROTEIN 1 (LATE PR... 47 6e-05 Query= sid|110161l1an|182ORF006 Phage 182 ORF114995-1602611 (343 letters) gi|137945IsplP0754lVG16_BPPZA ENCAPSIDATION PROTEIN (LATE PROT ... 402 e-112 gijl37944|spjPll014|VG16_BPPH2 ENCAPSIDATION PROTEIN (LATE PROT ... 402 e-112 Query= sid|110162|lanh182ORF007 Phage.182 ORF17795-877511 (326 letters) gil137915|spjP07535|VG10_BPPZA UPPER COLLAR PROTEIN (CONNECTOR ... 256 3e-68 gij1379l4|sp|P04332|VG10_BPPH2 UPPER COLLAR PROTEIN (CONNECTOR ... 256 5e-68 Query= sidtl10163|1an|182ORF008 Phage 182 ORF114105-1498312 (292 letters) gil462559|spIP34020ILYC_CLOAB AUTOLYTIC LYSOZYME (1,4-BETA-N-AC... 75 2e-13 gijl266521spIP25310|LYCMSTRGL LYSOZYME M1 PRECURSOR (1,4-BETA-... 60 Se-09 gi|1277891spIP19386|LYCABPCP9 LYSOZYME (ENDOLYSIN) (MURANIDASE... 60 Se-09 gi11277871spIP15057|LYCABPCP1 LYSOZYME (ENDOLYSIN) (MURAMIDASE... 57 4e-08 gil126597|spjP00721ILYCHCHASP N,O-DIACETYLMURAMIDASE (LYSOZYME... 57 4e-08 gijl27788|sp|P19385LYCABPCP7 LYSOZYME (ENDOLYSIN) (MURAMIDASE ... 57 5e-08 gil3025168[sp|P76421|YEGX_ECOLI HYPOTHETICAL 32.0 KD PROTEIN IN... 53 5e-07 Query= sid|110164|lanh182ORF009 Phage 182 ORF18765-960112 (278 letters) gij137921jsplP04333|VG11_BPPH2 LOWER COLLAR PROTEIN (LATE PROTE... 171 le-42 gi|131782jspjP12753|RA50_YEAST DNA REPAIR PROTEIN RAD50 (153 KD... 48 2e-05 gijl76490|spjP40889jYJW5_YEAST HYPOTHETICAL 197.6 KD PROTEIN I... 45 le-04 gil731903|spIP40434|YIR7_YEAST HYPOTHETICAL 197.5 KD PROTEIN IN... 45 le-04 gil7302751sp|P39793|PBPABACSU PENICILLIN-BINDING PROTEINS 1A/1... 45 2e-04 gij1168610|spjP41696jAZF1_YEAST ASPARAGINE-RICH ZINC FINGER PRO... 44 3e-04 WO 00/32825 PCT/IB99/02040 giJ7315871spIP389001YH19_YEAST HYPOTHETICAL 70.1 KD PROTEIN IN ... 44 3e-04 Query= sid|110165lan|182ORF010 Phage 182 ORF11310-215512 (281 letters) gil1356041spjP06812|TERMBPNF DNA TERMINAL PROTEIN 69 8e-12 Query= sid|110166IlanJ182ORF011 Phage 182 ORF19607-1015811 (183 letters) gil1379281spJP075371VG12_BPPZA PRE-NECK APPENDAGE PROTEIN (LATE... 51 2e-06 gi11379271spJP203451VG12_BPPH2 PRE-NECK APPENDAGE PROTEIN (LATE... 50 3e-06 Query= sid|110169l1an|182ORF014 Phage 182 ORF113716-1410813 (130 letters) gil1379361splP111881VG14_BPPH2 LYSIS PROTEIN (LATE PROTEIN GP14) 97 2e-20 gij1379381spjP07539|VG14_BPPZA LYSIS PROTEIN (LATE PROTEIN GP14) 96 2e-20 Query= sid|110170|1anh182ORF015 Phage 182 ORF1854-122512 (123 letters) gil1380721spIP06953|VG5A_BPPZA EARLY PROTEIN GP5A 69 2e-12 Query= sid|l10174|1anI182ORF019 Phage 182 ORF14323-461313 (96 letters) gil138111|splP13848|VG7_BPPH2 HEAD MORPHOGENESIS PROTEIN (LATE ... 57 9e-09 gil1381121spIP075331VG7_BPPZA HEAD MORPHOGENESIS PROTEIN (LATE ... 54 4e-08 Query= sidI1lO180|lanh182ORF025 Phage 182 ORF1548-81412 (88 letters) gil138099IspjP069551VG6_BPPZA EARLY PROTEIN GP6 55 2e-08 gil138098JspP03685|VG6_BPPH2 EARLY PROTEIN GP6 54 5e-08 WO 00/32825 PCT/IB99/02040 334 BLASTP 2.0.8 [Jan-05-1999 Query= sid1110156|lanh182ORF001 Phage 182 ORF15966-778012 (604 letters) >gi|138124[spjP07534IVG9_BPPZA TAIL PROTEIN (LATE PROTEIN GP9) >gi175849|pir IWMBP9Z gene 9 protein - phage PZA >gi1216058 (M11813) tail protein (Bacteriophage PZA] Length = 599 Score = 384 bits (975), Expect = e-105 Identities = 231/610 (37%), Positives = 344/610 (55%), Gaps = 36/610 (5%) Query: 6 TNVKLLANVPFDNTYTHTRWFKTQQEQESYFNSFPVLNENRDCSYQRDTQLGGVFRVDKH 65 TNV++LA+VPF N Y +TRWF + Q ++FNS + E ++Q + V Sbjct: 9 TNVRILADVPFSNDYKNTRWFTSSSNQYNWFNSKTRVYEMSKVTFQGFRENKSYISVSLR 68 Query: 66 KDALYACNYLIFKNEETYPSKWQYAFVTDIEYKNDNTSFVTFEIDVLQTYRFDIGIRESF 125 D LY +Y++F+N + Y +KW YAFVT++EYKN T++V FEIDVLQT+ F+I +ESF Sbjct: 69 LDLLYNASYIMFQNAD-YGNKWFYAFVTELEYKNVGTTYVHFEIDVLQTWMFNIKFQESF 127 Query: 126 IAKEHPQLYYSNGIPFINTIEESLDYGREYTTTNVTTFHPNDGVNFLVILTSEAM--PVG 183 I +EH +L+ +G P INTI+E L+YG EY +V P D + FLV+++ M G Sbjct: 128 IVREHVKLWNDDGTPTINTIDEGLNYGSEYDIVSVENHRPYDDMMFLVVISKSIMHGTAG 187 Query: 184 DKEDKSG---GSIVGGPSPFSYYLLPINSSGEVYKPN-GAGNANFGEYMAFLT-- -TKEP 236 + E + S+ G P P YY+ P G+V K G NAN + LT +++ Sbjct: 188 EAESRLNDINASLNGMPQPLCYYIHPFYKDGKVPKTFIGDNNANLSPIVNMLTNIFSQKS 247 Query: 237 FLNKIVGMYVTSYTGIPFIVDHANKTVRYNAGGSYKIMLPTYASDPTGTMKTFAFFCVKE 296 +N IV MYVT Y G+ + +K ++ + + + A D G + T VK+ Sbjct: 248 AVNNIVNMYVTDYIGLKLDYKNGDKELKLDKDMFEQAGI --- ADDKHGNVDTIF-- -VKK 301 Query: 297 ARTFVPKRIDLVGNVYNYFREAFPFNVKESKLFMYPYCLIEITDTKGHVMTLRPEYLTGG 356 + ID G+ + F + +ESKL MYPYC+ E+TD KG+ M L+ EY+ Sbjct: 302 IPDYETLEID-TGDKWGGFTKD-----QESKLMMYPYCVTEVTDFKGNHMNLKTEYIDNN 355 Query: 357 KLSVYVKGSLGISNKVMIEPIDYDVSNSTI----ITNLSDKMLIDNDPNDVGVKSDYASA 412 KL + V+GSLG+SNKV DY+ S +T D LI+N+PND+ + +DY SA Sbjct: 356 KLKIQVRGSLGVSNKVAYSIQDYNAGGSLSGGDRLTASLDTSLINNNPNDIAIINDYLSA 415 Query: 413 FMQGNKNSLIAQEQNIRNTFRHGMGNSAMSTGGAIFSALASNNPFVGLTNIMGAGQQVNN 472 ++QGNKNSL Q+ +I GM +S G ++ +PF +++ G N Sbjct: 416 YLQGNKNSLENQKSSILFNGIVGMLGGGVSAG ---- ASAVGRSPFGLASSVTGMTSTAGN 471 Query: 473 YVSEKENGLNLLAGKVADIENIPDNVTQLGSNLSFTTGN-FQNYYQLRFKQIKYEYATRL 531 V + + L K ADI NIP +T++G N +F GN ++ Y ++ KQ+K EY L SbjCt: 472 AVLD ---- MQALQAKQADIANIPPQLTKMGGNTAFDYGNGYRGVYVIK-KQLKAEYRRSL 526 Query: 532 DRYFSMYGTKSNRVATPNLQTRKAWNFIKLKEPNIVGTMSNDVLTRVKQIFSAGVTLWHT 591 +F YG K NRV PNL+TRKA+N+I+ K+ I G ++N+ L ++ IF G+TLWHT Sbjct: 527 SSFFHKYGYKINRVKKPNLRTRKAYNYIQTKDCFISGDINNNDLQEIRTIFDNGITLWHT 586 Query: 592 NDVLNYNQDN 601 +D+ NY+ +N Sbjct: 587 DDIGNYSVEN 596 Query= sid110157|1anl182ORF002 Phage 182 ORFI2152-387311 (573 letters) >gif118848|spIP19894|DPOLBPM2 DNA POLYMERASE >gi|76896|pir|IJQ0161 DNA-directed DNA polymerase (EC 2.7.7.7) - phage M2 >gil215509 (M33144) DNA polymerase (Bacteriophage M2] - Length = 572 Score = 665 bits (1697), Expect = 0.0 Identities = 327/589 (55%), Positives = 420/589 (70%), Gaps = 38/589 (6%) Query: 3 KKYTGDFETTTDLNDCRVWSWGVCDIDNVDNMTFGLEIDSFFEWCKMQGSTDIYFHNEKF 62 K ++ DFETTT L+DCRVW++G +I N+DN G +D F +W M+ D+YFHN KF WO 00/32825 PCT/IB99/02040 335 Sbjct: 4 KMFSCDFETTTKLDDCRVWAYGYMEIGNLDNYKIGNSLDEFMQWV-MEIQADLYFHNLKF 62 Query: 63 DGEFMLSWLFKNGFKWCKEAKEDRTFSTLISNMGQWYALEICWEVNYXXXXXXXXXXXXX 122 DG F+++WL ++GFKW E + T++T+IS MGQWY ++IC+ Sbjct: 63 DGAFIVNWLEQHGFKWSNEGLPN-TYNTIISKMGQWYMIDICFGYK---------GKRKL 112 Query: 123 XXIIYDSLKKYPFPVKQIAEAFNFPIKKGEIDYTKERPIGYKPTKDEWEYLKNDIQIMAM 182 +IYDSLKK PFPVK+IA+ F P+ KG+IDY ERP+G++ T +E+EY+KNDI+I+A Sbjct: 113 HTVIYDSLKKLPFPVKKIAKDFQLPLLKGDIDYHTERPVGHEITPEEYEYIKNDIEIIAR 172 Query: 183 ALKIQFDQGLTRMTRGSDALGDYKDWLKATHGKSTFKQWFPILSLGFDKDLRKAYKGGFT 242 AL IQF QGL RMT GSD+L +KD L F + FP LSL DK++RKAY+GGFT Sbjct: 173 ALDIQFKQGLDRMTAGSDSLKGFKDILST----KKFNKVFPKLSLPMDKEIRKAYRGGFT 228 Query: 243 WVNKVFQGKEIGDGIVFDVNSLYPSQMYVRPLPYGTPLFYEGEYKPNNDYPLYIQNIKVR 302 W+N ++ KEIG+G+VFDVNSLYPSQMY RPLPYG P+ ++G+Y+ + YPLYIQ I+ Sbjct: 229 WLNDKYKEKEIGEGMVFDVNSLYPSQMYSRPLPYGAPIVFQGKYEKDEQYPLYIQRIRFE 288 Query: 303 FRLKEGYIPTIQVKQSSLFIQNEYLESSVNKLGVDELIDLTLTNVDLELFFEHYDILEIH 362 F LKEGYIPTIQ+K++ F NEYL++S GV E ++L LTNVDLEL EHY++ + Sbjct: 289 FELKEGYIPTIQIKKNPFFKGNEYLKNS----GV-EPVELYLTNVDLELIQEHYELYNVE 343 Query: 363 YTYGYMFKASCDMFKGWIDKWIEVKNTTEGARKANAKGMLNSLYGKFGTNPDITGKVPYM 422 Y G+ F+ +FK +IDKW VK EGA+K AK MLNSLYGKF +NPD+TGKVPY+ Sbjct: 344 YIDGFKFREKTGLFKDFIDKWTYVKTHEEGAKKQLAKLMLNSLYGKFASNPDVTGKVPYL 403 Query: 423 GEDGIVRLTLGEEELRDPVYVPLASFVTAWGRYTTITTAQKCFDRIIYCDTDSIHLVGTE 482 +DG + +G+EE +DPVY P+ F+TAW R+TTIT AQ C+DRIIYCDTDSIHL GTE Sbjct: 404 KDDGSLGFRVGDEEYKDPVYTPMGVFITAWARFTTITAAQACYDRIIYCDTDSIHLTGTE 463 Query: 483 VPEAIDHLVDPKKLGYWGHESTFQRAKFIRQKT-----YVEEIDGEL-------------- 524 VPE I +VDPKKLGYW HESTF+RAK++RQKT YV+E+DG+L Sbjct: 464 VPEIIKDIVDPKKLGYWAHESTFKRAKYLRQKTYIQDIYVKEVDGKLKECSPDEATTTKF 523 Query: 525 NVKCAGMPDRIKEIVTFDNFEVGFSSYGKLLPKRTQGGVVLVDTMFTIK 573 +VKCAGM D IK+ VTFDNF VGFSS GK P + GGVVLVD++FTIK Sbjct: 524 SVKCAGMTDTIKKKVTFDNFAVGFSSMGKPKPVQVNGGVVLVDSVFTIK 572 Query= sid|110159lan|182ORF004 Phage 182 ORF14626-595413 (442 letters) >giI138117spIP13849VG8_BPPH2 MAJOR HEAD PROTEIN (LATE PROTEIN GP8) >gi|75845|pir1|WMBP89 gene 8 protein - phage phi-29 >gil215325 (M14782) major head protein [Bacteriophage phi-29] >gil225362|prfI 11301270B gene 8 [Bacillus sp.] Length = 448 Score = 309 bits (783), Expect = 2e-83 Identities = 176/440 (40%), Positives = 250/440 (56%), Gaps = 27/440 (6%) Query: 4 KITEQDVLRATNVETPVQLMTAIYNSSSSLFQANVPMPNADNIEAVGAGITRLDVVKNEF 63 +IT DV + + ++ AI NS F++ VP+ A+N+ VGAGI V+N+F Sbjct: 2 RITFNDVKTSLGITESYDIVNAIRNSQGDNFKSYVPLATANNVAEVGAGILINQTVQNDF 61 Query: 64 ISTLVDRIGKVVIRYKSWRNPLKMFKKGNMPLGRTIEEIFVDIAQEHKFNPDESVTGVFK 123 I++LVDRIG VVIR S NPLK FKKG +PLGRTIEEI+ DI +E +++ +E+ VF+ Sbjct: 62 ITSLVDRIGLVVIRQVSLNNPLKKFKKGQIPLGRTIEEIYTDITKEKQYDAEEAEQKVFE 121 Query: 124 QEVPDVKTLFHEINREGYYKQTIQEAWLEKAFTSWDNFNSFVAGVMNALYTGDEVSEFEY 183 +E+P+VKTLFHE NR+G+Y QTIQ+ L+ AF SW NF SFV+ ++NA+Y EV E+EY Sbjct: 122 REMPNVKTLFHERNRQGFYHQTIQDDSLKTAFVSWGNFESFVSSIINAIYNSAEVDEYEY 181 Query: 184 TKLLIANYQEKELFKEIEIGEITESNA--KEFIRKIKSTSNKLEFM--SSAYNAQGVKTS 239 KLL+ NY K LF ++I E T S EF++K+++T+ KL S +N+ V+T Sbjct: 182 MKLLVDNYYSKGLFTTVKIDEPTSSTGALTEFVKKMRATARKLTLPQGSRDWNSMAVRTR 241 Query: 240 TSKSDQYXXXXXXXXXXXXXXXXXXFNMSKTDFVGHKIVIDEFPKKEGEESSNIVAVIV 299 + D + FNM++TDF+G+ VID F S+ + AV+V Sbjct: 242 SYMEDLHLIIDADLEAELDVDVLAKAFNMNRTDFLGNVTVIDGF ------ ASTGLEAVLV 295 Query: 300 DSEWFMIYDKLYKTTSLYNPEGLYWNYWLHHHQLYSTSQFGNAVAFVKSATKPVTKVAFA 359 D +WFM+YD L+K ++ NP GLYWNY+ H Q S S+F NAVAFV VT+V + Sbjct: 296 DKDWFMVYDNLHKMETVRNPRGLYWNYYYHVWQTLSVSRFANAVAFVSGDVPAVTQVIVS 355 Query: 360 SATTSVVKGSSKDIALTFTPVEATNQQGEVVSSAPALVKATVKQTAGKATAVTVEGLEVG 419 WO 00/32825 PCT/IB99/02040 336 +V +G + V ATN + V V G +T + G Sbjct: 356 PNIAAVKQGGQQQFT---AYVRATNAKDHKV----------VWSVEGGSTGTAI----TG 398 Query: 420 QSLVTFTAIGGQQATVLVTV 439 L++ + Q TV TV Sbjct: 399 DGLLSVSGNEDNQLTVKATV 418 Query= sid11101601an|182ORF005 Phage 182 ORF112651-1370013 (349 letters) >gii137932|sp|P151321VG13_BPPH2 MORPHOGENESIS PROTEIN 1 (LATE PROTEIN GP13) >gij75858jpir||WMBP23 gene 13 protein phage phi-29 >gij215331 (M14782) morphogenesis protein (Bacteriophage phi-29} >gil2253681prf1|1301270H gene 13 (Bacteriophage phi-29] Length = 365 Score = 51.5 bits (121), Expect = 8e-06 Identities = 44/166 (26%), Positives = 70/166 (41%), Gaps = 14/166 (8%) Query: 6 NEQIARGQTIAKILSKYGYNKNSQVGVVANLHWESA--- GLNPNSNEXXXXXXXXX-QWT 61 +E Q I LS G+ K + G++ N+ ES GL N +E QWT Sbj ct: 12 SEMKVNAQYILNYLSSNGWTKQAICGMLGNMQSESTINPGLWQNLDEGNTSLGFGLVQWT 71 Query: 62 PKSNLYRQAQICGLSNAKAETLEGQAEIIAQGDKTGQWMDNTPVSSAGYTNPQTLSAFKQ 121 P SN A GL ++ II + + QW++ ++ Y K Sbj ct: 72 PASNYINWANSQGLPYKDMDS- -ELKRIIWEVNNNAQWINLRDMTFKEY -------- IKS 121 Query: 122 SANIDVATINFMCHWERPGKLHIEERLDLAQAYSKHIDGSGGGGVK 167 + + F+ +ERP + ER D A+ + K++ G GGGG++ Sbjct: 122 TKTPRELAMIFLASYERPANPNQPERGDQAEYWYKNLSGGGGGGLQ 167 Query= sid|1101611lan182ORF006 Phage 182 ORF114995-1602611 (343 letters) >gil137945|spIP075411VG16_BPPZA ENCAPSIDATION PROTEIN (LATE PROTEIN GP16) >gij75861jpirjWMBP16 gene 16 protein - phage PZA >gil216065 (M11813) morphogenesis protein C (Bacteriophage PZA] Length = 332 Score = 402 bits (1023), Expect = e-111 Identities = 186/332 (56%), Positives = 244/332 (73%), Gaps = 2/332 (0%) Query: 11 EKNLYYNPNNALGFNCLMLFVIGARGIGKTYGYKKFVVNRFIKHGEQFIYLRRFKTELKK 70 +K+L+YNP L ++ ++ FVIGARGIGK+Y K + +NRFIK+GEQFIY+RR+K EL K Sbjct: 2 DKSLFYNPQKMLSYDRILNFVIGARGIGKSYAMKVYPINRFIKYGEQFIYVRRYKPELAK 61 Query: 71 IPQFFKTMAKEFPDHKLEVKGKEFYCDDKLMGWAVPLSTWGIEKSNEYPEVRTILFDEFL 130 + +F +A+EFPDH+L VKG+ FY D.KL GWA+PLS W EKSN YP V TI+FDEF+ Sbjct: 62 VSNYFNDVAQEFPDHELVVKGRRFYIDGKLAGWAIPLSVWQSEKSNAYPNVSTIVFDEFI 121 Query: 131 IEKSKITYLPNEAEALLNMMETVFRRRTNTRCVMLSNATSVVNPYFLYFNLQPDLNKRFN 190 EK Y+PNE ALLN+M+TVFR R RC+ LSNA SVVNPYFL+FNL PD+NKRFN Sbjct: 122 REKDNSNYIPNEVSALLNLMDTVFRNRERVRCICLSNAVSVVNPYFLFFNLVPDVNKRFN 181 Query: 191 LYQDRGILIELCDSKDFAEVKRETPFGRLIRGTEYEDFSINNEFVNDSDTFIEKRSKNSS 250 +Y D LIE+ DS DF+ +R+T FGRLI GTEY + S++N+F+ DS FIEKRSK+S Sbjct: 182 VYDD--ALIEIPDSLDFSSERRKTRFGRLIDGTEYGEMSLDNQFIGDSHVFIEKRSKDSK 239 Query: 251 FLCAIAFEGKIFGYWIDAETGCVYVSYDYQPNTNHFYAMTTKDHEENRLLMKNWRNNYYL 310 F+ +I + G G W+D G +YV + P+T + Y +TT D EN +L+ N++NNY+L Sbjct: 240 FVFSIVYNGFTLGVWVDVNQGLMYVDTAHDPSTKNVYTLTTDDLNENMMLITNYKNNYHL 299 Query: 311 STVAKAFKNSYLRFDNIVIKNLHYDLFNKMKI 342 +A AF N YLRFDN VI+N+ Y+LF KM+I Sbjct: 300 RKLASAFMNGYLRFDNQVIRNIAYELFRKMRI 331 Query- sid|110162lan182RF007 Phage 182 ORFI7795-877511 (326 letters) >gij1429239|embICAA676581 (X99260) upper collar protein (Bacteriophage B103] WO 00/32825 PCT/IB99/02040 Length = 308 Score = 271 bits (685), Expect = 6e-72 Identities = 131/275 (47%), Positives = 187/275 (67%), Gaps = 5/275 (1%) Query: 36 YYEHYRRQLTLLTFQLFEWENLPKSIDPRYLEIALHTNGYLGFFKDPTLGFMVCAGAEDG 95 +Y HY + L L +QLFEWE LP S+DP YLE ++H GY+GF+KDP +G++ C GA G Sbjct: 22 WYYHYYQYLCSLAYQLFEWERLPPSVDPSYLEKSIHQFGYVGFYKDPRIGYIACQGALSG 81 Query: 96 QIDHYHNPIFFTANEAMYHKRYPVLRYDDDDDKSKCIMLYNNDLKVPTLPSLHRFALDMA 155 +DHY+ P F A+ Y + + Y D +K+ + +YNNDLK TLP+L FA D+A Sbjct: 82 TVDHYNLPDRFHASSVGYQNTFKLYNYSDMKEKNMGVAIYNNDLKCSTLPALEMFAQDLA 141 Query: 156 DINQISRVNRRAQKTPVIIQTDEKKYFSLLQAYNQIDENNQAVFVDKDMEFDESFNVWQT 215 ++ +I VN+ AQKTPV+I ++ SL YNQ + N +FV + ++ D + V++T Sbjct: 142 ELKEIIAVNQNAQKTPVLIAANDNNQLSLKNIYNQYEGNAPVIFVHESLDLD-NLKVFKT 200 Query: 216 NAPYVVDKLRSELNEVWNEVLTFLGINNANVDKTARVQTSEVLSNNEQIESSGNILLKSR 275 +APYVVDKL ++ N VWNEV+T+LGI NAN++K R+ TSEV SN+EQIESSGNI LK+R Sbjct: 201 DAPYVVDKLNAQKNAVWNEVMTYLGIKNANLEKKERMVTSEVDSNDEQIESSGNIYLKAR 260 Query: 276 KEFCDRVNRVFGDELDGKIDVKFRTDAVRQLQLAA 310 +E C++++ ++G L VKFR D V Q++L A Sbjct: 261 QEACNKISELYGLNL----KVKFRYDIVEQMRLNA 291 Query= sidIlO163|1an|l82ORFOO8 Phage 182 ORF114105-1498312 (292 letters) >gil4210750embICAA10710| (AJ132604) LysL protein [Lactococcus lactis] Length = 235 Score = 139 bits (347), Expect = 2e-32 Identities = 85/210 (40%), Positives = 114/210 (53%), Gaps = 14/210 (6%) Query: 2 MNGIDISSYQTGIDLSKVPCDFVNIKATGGTGYVNPDCDRAFQQALSLGKKIGVYHFAHE 61 MNGIDISSYQ ++ VP DFV IKAT GT Y+NP + Q + K +G YHFA Sbjct: 1 MNGIDISSYQAELNAGIVPSDFVIIKATEGTNYINPTWEEQAGQVIQTNKLLGFYHFAS- 59 Query: 62 RGLEGTPQQEAQFFLDNIKGYIGKAVLILDFEGS--NQKDVNWAKAFLDYVYNKTGVKAW 119 G P EA FF+ +K YIGKAVL+LDFE N A+ FL+ V KTG+ Sbjct: 60 --- VGNPIAEADFFISVVKNYIGKAVLVLDFEAGAINAWGNVGARQFLNRVKEKTGINPM 116 Query: 120 FYTYTANLNTTDFSSIAKGDYGLWVAEYGSNQPQGYSQPAPPKTNN-----FPIVACFQF 174 Y + ++S+I+ + LWVA+Y S P GY + P T+ + A Q+ Sbjct: 117 IYMSSDVTRQFNWSTISSTN-PLWVAQYASMNPTGYQ--SEPWTDGKGYGAWSSAAIHQY 173 Query: 175 TSKGRLPGYNGNLDLNVFYGDGNTWDLYVG 204 +S G L ++GNLD+N+ Y + N W G Sbjct: 174 SSAGSLSNWSGNLDINLAYINANQWKSLAG 203 Query= sid110164I1an182ORFOO9 Phage 182 ORF18765-960112 (278 letters) >gil1429240|emb|CAA67659| (X99260) lower collar protein [Bacteriophage B103J Length = 293 Score = 180 bits (451), Expect = le-44 Identities = 115/296 (38%), Positives = 161/296 (53%), Gaps = 33/296 (11%) Query: 3 LKRYIESFTYYQPELSRKERIEVGRKQLFDFDYPFYDETKRAEFETKFINHFYLREIGSE 62 L YIE ++ Y+ LS E+IE GR +LFDF YP +DE+ R FET FI +FY+REIG E Sbjct: 8 LSTYIEMWSQYETGLSMAEKIEKGRPKLFDFQYPIFDESYRKVFETHFIRNFYMREIGFE 67 - Query: 63 TMGSFKFNLDEYLNLNMPYWNKMFLSNLEEF-PIFDDMDYTIDEKQKLLNEIDTNIKANR 121 T G FKFNL+ +L +NMPY+NK+F S L ++ P+ + T K+ DT NR Sbjct: 68 TEGLFKFNLETWLIINMPYFNKLFESELIKYDPLENTRLNTTGNKKN-----DTERNDNR 122 Query: 122 D-------ESKNQTKQVDQTDNRNKNTRDTGTT-----DSFSRNTYTDTPQKDLRIASNG 169 D + K+ TK D+T+ + D TT D+F+R +D P L + +N WO 00/32825 PCT/IB99/02040 338 Sbjct: 123 DTTGSMKADGKSNTKTSDKTNATGSSKEDGKTTGSVTDDNFNRKIDSDQPDSRLNLTTN- 181 Query: 170 DGTGVINYATNITEDLSKETTSSTGVETNNDKTNQNTRSNAS----------EKETKNTD 219 DG G + YA+ I E+ + ++TG TNN ++ + S S T N Sbjct: 182 DGQGTLEYASAIEENNTNNKRNTTG--TNNVTSSAESESTGSGTSDTVTTDNANTTTNDK 239 Query: 220 INKDQNQTKDTITRYKGKKGNTDYADLLEKYRRSVLRIEKMIFREMNKEGLFLLVY 275 +N N +D I GK G YA L++ YR ++LRIEK IF EM + LF+LVY Sbjct: 240 LNSQINNVEDYIESKIGKSGTQSYASLVQDYRAALLRIEKRIFDEMQE--LFMLVY 293 Query= sidI110165|lan|182ORF010 Phage 182 ORF11310-215512 (281 letters) >gil135604|spIP06812|TERMBPNF DNA TERMINAL PROTEIN >gil75815IpirIERBPNP terminal protein - phage NF >gi|579177jemb|CAA68440| (Y00363) gene E product (AA 1-267) [Bacteriophage NF] Length = 266 Score = 74.9 bits (181), Expect = 6e-13 Identities = 73/275 (26%), Positives = 129/275 (46%), Gaps = 37/275 (13%) Query: 3 VRISKNDRAKLEKIYGKSNKARKKYNRLRQK-GVE --- ERQLPTVPTSKKRLIDYVKSTN 58 +RI+ ND+A K+ K+ KA K +R ++K G++ E +LP ++ + Sbjct: 7 IRITNNDKALYAKLV-KNTKA--KISRTKKKYGIDLSNEIELPPLESFQ------------ 52 Query: 59 MSRSDFNKMLDELVDFAQPYNENYIFEINKRNVAISRAQIKEAQIKTEQAQKAKEEHYKE 118 +R +FNK + F N+NY F NK + S+A+I E T++AQ+ +E +E Sbjct: 53 -TREEFNKWKQKQESFTNRANQNYQFVKNKYGIVASKAKINEIAKNTKEAQRIVDEQREE 111 Query: 119 L--------NKVEVKKPTENTIVTPTILTELGADLPFQAIPDFNIDAFTSPEGVQSYLEN 170 + K + I++P+ +T G P DFN D S +++ E Sbjct: 112 IEDKPFISGGKQQGTVGQRMQILSPSQVT--GISRP----SDFNFDDVRSYARLRTLEEG 165 Query: 171 IG-KQDEQYFDERDQLYYDNFRQAMFTIFNSD--ADDIVRLLDSMGLDLFMKTYVSNFLD 227 + K Y+D R + NF + + FNSD +D++V L + D F + Y+ F + Sbjct: 166 MAEKASPDYYDRRMTQMHQNFIEIVEKSFNSDWLSDELVERLKKIPPDDFFELYLM-FDE 224 Query: 228 MNLDYIYDEAEVQQKKEQVYSKIAKVIESETGGEV 262 ++ +Y E E + E + +KI ++ G+V Sbjct: 225 ISFEYFDSEGEDVEASEAMLNKIHSYLDRYERGDV 259 Query= sidI10166|lan|182ORF011 Phage 182 ORF19607-1015811 (183 letters) >gil1429241lembICAA67660| (X99260) pre-neck appendage protein [Bacteriophage B1031 Length = 860 Score = 50.8 bits (119), Expect = 6e-06 Identities = 29/105 (27%), Positives = 56/105 (52%), Gaps = 6/105 (5%) Query: 8 KRFDGLPAVFKERFSKYPHTEYRYELLLDEEVSALIAYLNEVGALVNDMSGYLNYFIEHF 67 +RF+ L + + + +Y T + + L E+++ +I YLN++G L ND+ N +E Sbjct: 7 RRFEKLGEMMVQVYERYLPTAFDESMTLLEKMNKIIEYLNQIGRLTNDVVEEWNKVMEWI 66 Query: 68 V-EKLEEITNDTLKKWLSDGTLENLINDTVFANYIKEIKRLQILV 111 + + LE+ +TL+KW +G +L+ I E+K+ + V Sbjct: 67 LNDGLEDYVKETLEKWYEEGKFADLV-----IQVIDELKQFGVSV 106 Query- sid|110169|1anIl82ORF014 Phage 182 ORF113716-1410813 (130 letters) >gi|l37936|sp|P11188|VG14_BPPH2 LYSIS PROTEIN (LATE PROTEIN GP14) >gil75860|pir||WMBP29 gene 14 protein - phage phi-29 >gil15678|embICAA28631| (X04962) gene 14 product (AA WO 00/32825 PCT/IB99/02040 339 1-393) [Bacteriophage phi-29] >giI225369|prf|11301270J gene 14 [Bacteriophage phi-29 Length = 131 Score = 96.7 bits (237), Expect = 6e-20 Identities = 53/131 (40%), Positives = 81/131 (61%), Gaps = 3/131 (2%) Query: 1 MIEYITQWL-ADDNHLVYGLIIWLMVAMIIDFVLGFTIAKFNKEIDFSSFKAKAGIIVKV 59 MI ++ +L D+ L+Y L +LMV M++D VLG AK N I FSSFK K G.+++KV Sbjct: 3 MIAWMQHFLETDETKLIYWLT-FLMVCMVVDTVLGVLFAKLNPNIKFSSFKIKTGVLIKV 61 Query: 60 AEMVLVVYFIPVAVKFGAVGITMYITMLVGLILSEIYSILGHISDIDDDNNWTDYVKKFL 119 +EM+L + IP AV F A G+ + T+ L +SEIYSI GH+ +DD +++ + ++ F Sbjct: 62 SEMILALLAIPFAVPFPA-GLPLLYTVYTALCVSEIYSIFGHLRLVDDKSDFLEILENFF 120 Query: 120 DGTLNRKDDIK 130 T + + K Sbjct: 121 KRTSGKNKEEK 131 Query= sidIl10170I1an|l82ORF015 Phage 182 ORF1854-122512 (123 letters) >gil15670lembICAA24483| (VO1155) reading frame 10 (may be gene 4) [Bacteriophage phi-29] Length = 124 Score = 69.9 bits (168), Expect = 6e-12 Identities = 39/119 (32%), Positives = 64/119 (53%), Gaps = 3/119 (2%) Query: 3 IVKSTFDTQTPEGMLQVFNATNGASIPLRNAI-GEVLELKDILVYSDEVSGFGGAEPSQA 61 IVK+TFDT+T EG +++FNA G +N G ++E I Y +G A+ + Sbjct: 6 IVKATFDTETLEGQIKIFNAQTGGGQSFKNLPDGTIIEANAIAQYKQVSDTYGDAK--EE 63 Query: 62 ELVAFFTEDGKTYAGVSAVATKSAKNLIDMMTANPDIKPKISFVEGKSNGGQKFVNLQV 120 + F DG Y+ +S ++A +LID++T + K+ V+G S+ G F +LQ+ Sbjct: 64 TVTTIFAADGSLYSAISKTVAEAASDLIDLVTRHKLETFKVKVVQGTSSKGNVFFSLQL 122 Query- sidl11017411ani182ORF019 Phage 182 ORF14323-461313 (96 letters) >gi11429235|emb|CAA676541 (X99260) head morphogenesis protein [Bacteriophage B103] Length = 101 Score = 60.9 bits (145), Expect = le-09 Identities = 34/96 (35%), Positives = 53/96 (54%), Gaps = 5/96 (5%) Query: 1 MEIKEHESILNGILESVTDGEARSKIVEHLEALREDYGATTEALTSANSTLEKLKKDNEA 60 ME HE ILN + + + R+.+ L+ LR DYG+ + S EKL+ +N Sbjct: 3 MERDSHEEILNKLNDPELEHSERTEL---LQQLRADYGSVLSEFSELTSATEKLRAENSD 59 Query: 61 LVISNSKLFRERAIVEPAEN--NEPETDQNITLDDL 94 L++SNSKLFR+ I + E + E + IT++DL Sbjct: 60 LIVSNSKLFRQVGITKEKEEEIKQEELSETITIEDL 95 Query= sid1110180lan|182ORF025 Phage 182 ORF1548-81412 (88 letters) >gi|138099|sp|P06955|VG6_BPPZA EARLY PROTEIN GP6 >gi|75841jpirj|ERBP6Z gene 6 protein - phage PZA >gil216047 (M11813) gene 6 product [Bacteriophage PZA] >giJ224746|prf|11112171K ORF 6 [Bacteriophage PZA] Length = 96 Score = 55.0 bits (130), Expect = 8e-08 Identities = 28/79 (35%), Positives = 45/79 (56%) WO 00/32825 PCT/I B99/02040 340 Query: 4 KLMQRNVTSTKVEFSEVIVQDGAPTIVPCEPVVLTGK(LSEEKALSAIKRKNPDKNVVVTN 63 K+MQR +T TV .....+DG + G LS E+A +KRK + VV + Sbj Ct: 3 KMMQREITKTTVNVAKMVMVDGEVQVEQLPSETFVGNLSMEQAQWRMKRKYKGEPVQVVS 62 Query: 64 VSHETALYTMPVDKFIELA 82 V T +Y +PV+KF+E+A Sbjct: 63 VEPNTEVYELPVEKFLEVA 81 WO 00/32825 PCT/IB99/02040 341 Table 26 Secondary structure prediction for ORF 1820RF008 1 MMNGIDISSY QTGIDLSKVP CDFVNIKATG GTGYVNPDCD RAFQQALSLG KKIGVYHFAH CCCCCCCCCC CCCCCCCCCC CCEEEEEECC CCCCCCCCCC HHHHHHHHHC CCCCEEEEEE 61 ERGLEGTPQQ EAQFFLDNIK GYIGKAVLIL DFEGSNQKDV NWAKAFLDYV YNKTGVKAWF CCCCCCCCHH HHHHHHHHHC CCCCEEEEEE CCCCCCCHHH HHHHHHHHHH HCCCCCEEEE 121 YTYTANLNTT DFSSIAKGDY GLWVAEYGSN QPQGYSQPAP PKTNNFPIVA CFQFTSKGRL EEECCCCCCC CCCEECCCCC CEEEEECCCC CCCCCCCCCC CCCCCCCEEE EEEECCCCCC 181 PGYNGNLDLN VFYGDGNTWD LYVGKKQDQI VPPENKIFDA TSDEFIFTLT TGSTSVFYFD CCCCCCCCEE EEECCCCCCE EEECCCCCCC CCCCCCCCCC CCCEEEEEEC CCCCEEEECC 241 GETIFELSDP TQLDHIRGTY NHVHGKEIPS MVWTPEQFDI YLKMYEKKPV YK CCEEEECCCC CCHHHHCCEE CCCCCCEECC CCCCCCCHHH HHHHHCCCCE EC Secondary structure prediction for ORF 1820RF014 1 MIEYITQWLA DDNHLVYGLI IWLMVAMIID FVLGFTIAKF NKEIDFSSFK AKAGIIVKVA CCCCEECCCC CCCCHHHHHH HHHHHHHHHH HHHHHHHHHC CCCCCHHHHH HHHCEEEEEE 61 EMVLVVYFIP VAVKFGAVGI TMYITMLVGL ILSEIYSILG HISDIDDDNN WTDYVKKFLD EEEEEEEECC CEEECCCEEE EEEEEEEEEE EEEEEEEECC CCCCCCCCCC CEEEEEEECC 121 GTLNRKDDIK
CCCCCCCEEC
WO 00/32825 PCT/IB99/02040 342 Table 27 Enterococcus accession numbers 242/242 gil2895751|gblAF044978.1|AF044978 [2895751] gil40982671gbIU76614.11BLU76614 [4098267] gil4803755|dbjlAB026843.11AB026843 [4803755] gil47019|emblY00116.1|SFAMB1 [47019] gil476900l IgblAF140549.1 1AF140549 [4769001] gil4158179|embjAL035206.I|SC9B5 [4158179] gil4760901|gb[AF099088.11AF099088 [4760901] gil4165458IemblX79343.1|EF16SSPA [4165458] gil4704705|gblAF121254.1|AF121254 [4704705] gil4165457|embIX79342.1|EFTRNALA [4165457] gil33421171gblAF076604.1|AF076604 [3342117] gil4165456|emblX79341.11EF23SRNA [4165456] gil4688824|emblAJ132470. 1ESP132470 gil41509781emb1Y14027.1 EFY14027 [4150978] [4688824] gil4127803lemblAJ223161.1IEFAJ3161 [4127803] gil47320851gblAF125553.11AF125553 [4732085] giI2956685lemblY16413.11EFENTIJO [2956685] gil4732082|gbIAF125552.11AF125552 [4732082] gi2665346jemblY13922.1 EHY13922 [2665346] gil47320791gblAF125551.11AF125551 [4732079] gij4324675gblAFlO9375. 1AF109375 [4324675] gil4732076|gblAF125550.1|AF125550 [4732076] gil4234627gblAFO61013.1IAFO61013 [4234627] gil47320731gbjAF125548.1|AF125548 [4732073] gil42346261gbAFO61012.11AFO61012 [4234626] gil4732070gblAF125547.1IAF125547 [4732070] gil42346251gbAFO61011.1IAFO61011 [4234625] gil4732067|gb[AF125546.1|AF125546 [4732067] gil4234624gbAFO61010.1jAFO61010 [4234624] gij4732064gblAF125545.1 AF125545 [4732064] gi4234623gblAFO61009.1 AF061009 [4234623] gil47320611gblAF125544.1IAF125544 [4732061] gi42346221gbAFO61008.1IAFO61008 [4234622] gil4704653|gb[AF114715.IIAF114715 [4704653] gil4234621gbAF0610071AF061007 [4234621] gil4704564|gblAF102550.1IAF102550 [4704564] gi4234620gbAFO61006.11AFO61006 [4234620] gil4688827lemb|AJ238249.11EFA238249 gij42346191gbJAFO61005.1IAFO6I005 [4234619] [4688827] gil4680606|gb[AF125198.1[AF125198 [4680606] gi42346181gbAF061004.11AF061004 [4234618] gil46332791gblAF 117609.1 AF 117609 [4633279] gi42346l71gblAFO61003.1IAFO61003 [4234617] gil46331241gblAF110130.1IAF110130 [4633124] gi42346161gbAF06100211AF061002 [4234616] gil45903991gblAF124258.11AF124258 [4590399] gil423461lSgbAFO61001.11AFO6IOO1 [4234615] gil4590336jgb|AF108380.1IAF108380 [4590336] gi14234614gbjAFO6 1000.1 AF061000 [4234614] gil45903351gblAF108379.1|AF108379 [4590335] gi3138990gblAF060241.11AF060241 [3138990] gil40191671gbIU21300.1|CXU21300 [4019167] gij31389861gbAF060240.11AF060240 [3138986] gil45451221gblAF077816.11AF077816 [4545122] gil42045351gbJAF094803.11AF094803 [4204535] gil4433610gblAF106614.1|AF106614 [4433610] gil42045341gblAF094802.11AF094802 [4204534] gil4468838|emblAJ132039.1|EFA132039 gil42045331gbAF094801.11AF094801 [4204533] [4468838] gil42045321gblAF094800.11AF094800 [4204532] gil4468121 emblAJ132958.1IBPH132958 gi420453 1 gblAF094799.1 AF094799-[4204534] [4468121] [4468121]gil4204530IgblAF094798. 1 AF094798 [4204530] gil4456104|emblY17302.1EHI17302 [4456104] gil42045291gbAF094797 1 1AF094797 [4204529] gil4433611|gblAF106615.1IAF106615 [4433611] gi4204528gbAF094796.11AF094796 [4204528] gil4433607igbAF106611.1AF106611 [4433607] gil42045275gblAF094795.1|AF094795 [4204527] WO 00/32825 PCT/IB99/02040 343 gil4204526|gblAF094794.11AF094794 [4204526] gil21498991gbIU94707.11EFU94707 [2149899] gil4204525|gblAF094793.1 AF094793 [4204525] gij21491491gb U82366.1LSU82366 [2149149] gil4204524|gblAF094792.11AF094792 [4204524] gi114694631gbIU49512.11EFU49512 [1469463] gil4204523|gblAF094791.1 AF094791 [4204523] gil1244503igbIU35366.11EFU35366 [1244503] gi[4204522|gblAF094790.1|AF094790 [4204522] gii8338541gbIU26268.I EFU26268 [833854] giJ4204521 gblAF094789. 1 IAF094789 [4204521] gil84l200jgbjUl8931.11CPU18931 [841200] gil4204520|gblAF094788.1|AF094788 [4204520] gil460079igbIUOO457.I1U00457 [460079] gil4204519|gblAF094787.11AF094787 [4204519] gil4600771gbjU00456.11U00456 [460077] gil42045181gblAF094786.11AF094786 [42045181 gil535661gbIL34675.1IINSTRANSPO [535661] gil42045171gblAF094785.1|AF094785 [4204517] gil302304lgblAF007787.11AF007787 [3023041] gil4204516|gblAF094784.11AF094784 [4204516] gil431124jgbIL15633.1 TRN9I6ENT [431124] gi[4204515|gblAF094783.11AF094783 [4204515] gil388106igbIL23802.11ENEEBSA [388106] gil4204514|gblAF094782. 1AF094782 [4204514] gil3608387lgbjAFO71085.1IAFO71085 [3608387] gil4204513|gblAF094781.1lAF094781 [4204513] gil35518511gblAF076027.11AF076027 [3551851] gil42045121gb|AF094780.1|AF094780 [4204512] gij355I7731gbIU94770.11SPU94770 [3551773] gil3873186|gblAF034779. 1AF034779 [3873186] gil35517431gb U57498.11ECU57498 [3551743] gil4l5l367|gblAF093508.11AF093508 [4151367] gil32431781gblAF063010.IIAFO63OIO [3243178] gil2828136|gblAF039903. 1AF039903 [2828136] gil3136316lgblAF063900.11AF063900 [3136316] gil2828135[gblAF039902.1|AF039902 [2828135] gil3540256[gblAFO52459.11AF052459 [3540256] gil2828134|gblAF039901.11AF039901 [2828134] gil7552151gbIU17696.1 LLU17696 [755215] gil2828133|gblAF039900.11AF039900 [2828133] gij34214371gblAF082295.11AF082295 [3421437] gil2828132[gblAF039899. 1AF039899 [2828132] gil34214361gblAFO82294.I AF082294 [3421436] gil2828131|gblAF039898.1|AF039898 [2828131] gij34214351gblAF082293.1 AF082293 [3421435] gil4103866|gblAF028812.1 lAF028812 [4103866] gil34214341gblAF082292.11AF082292 [3421434] gil4103864|gblAF028811.1lAF028811 [4103864] gil3341430lemblY17797.1 EFY17797 [3341430] gil26059251gblAF029727.1|AF029727 [2605925] gil3319647lembIX69092.1IEHPBP3RA [3319647] gil1402750IgblU60038.1|EFU60038 [1402750] gil3292886lemblAJ007584.11EFA7584 [3292886] gil1835780[gblU86375.I|EFU86375 [1835780] gi13261S36lembIALO2I958.1IMTVO41 [3261536] gil3831555|gblAF047608.11AF047608 [3831555] gil325O7O8lembIZ95150.1 MTCYI64 [3250708] gil37906171gblAF097414.1 AF097414 [3790617] gil32496881gblAF070678.11AF070678 [3249688] gil3767587ldbjlAB005036.1lAB005036 [3767587] gil3249687igblAF070677.1lAF070677 [3249687] gil3757810|gblAF042288.1|AF042288 [3757810] gil32496861gblAF070676.11AF070676 [3249686] gil37470391gblAF093509.1[AF093509 [3747039] gil3219 ldbjlABOlS233.11AB015233 [3219158] gil3660559ldbjlABO17811.1|AB017811 [3660559] gil2765275lembIY12924.I SPY12924 [2765275] gill 147743|gblU422 11.1|EHU42211 [1147743] gil3I83687lemblY11621.11EA16SRRN [3183687] gil3676412|gblAF051917.1|AF051917 [3676412] gil2765274lembIY12923.11EFYt2923 [2765_274i gil3676164|emblAJ011113.1|EFA011113 gil2765273lemblY12922.11ESY12922 [2765273] [3676164] gii2765272lemblY12921.11ESY12921 [2765272] gil2612869|gblAF005726.1AF005726 [2612869] gil2765271lemblYl292O.11EDY12920 [2765271] gil2337621gblAFO 16233.1 1AF016233 [2353762] gil27627lemblYI2919.IESY12919 [2765270] WO 00/32825 PCT/IB99/02040 344 gil2765269[emblY12918.1IECY12918 [2765269] gil20587621gbIB07882.11BO7882 [2058762] gil2765268|emblY12917.1IECY12917 [2765268] gil205876ligbIB07881,11B07881 [2058761] gil2765267lemb|Y12916.1|EPY12916 [2765267] gil2O5876O[gbIB07880.11B07880 [2058760] gil2765266|emb[Y12915.11ESY12915 [2765266] gil20587591gbIB07879.11B07879 [2058759] gil2765265[embIY12914.1IERY12914 [2765265] gil20587581gbIB07878.11BO7878 [2058758] gil2765264|emblY12913.1[EMY12913 [2765264] gi2O587571gbIB07877.11BO7877 [2058757] gil2765263[embIY12912.1|EHY12912 [2765263] gil20587561gbIB07876.11BO7876 [2058756] gil2765262|embjY12911.1IEMY12911 [2765262] gil20587551gbIB07875.11B07875 [2058755] gil27 6 52 6 1lemb|Y12910.1|EGY12910 [2765261] gil20587541gbIB07874.11B07874 [2058754] gil2765260|emb[Y12909.1|EDY12909 [2765260] gil2058753igbIB07863.11B07863 [2058753] gil2765259lemb|Y12908.lECY12908 [2765259] gil20587521gbIB07862.11B07862 [2058752] gil2765258|embIY12907.I|EAY12907 [2765258] gil205875l1gbIB07861.11B07861 [2058751] gil2765257|emb[Y12906.11EFY12906 [2765257] gil2058750igbIB07860.11B07860 [2058750] gil2765256|emblY12905.1|EFY12905 [2765256] gil20587491gbIB07859.11BO7859 [2058749] gil28945 4 1|emblAJ223332.11EFAJ3332 [2894541] gil20587481gbIB07858.11BO7858 [2058748] gil2894539lemblAJ223331.1[EFAJ3331 [2894539] gil2058747igbIB07857.11BO7857 [2058747] gil31080581gblAF060881.11AF060881 [3108058] gil20587461gbIB07856.11BO7856 [2058746] gil3087776|emblAJ223633.1IEFAJ3633 [3087776] gil20587451gbIB07855.11B07855 [2058745] gil30807541gb|AF016483.1|AF016483 [3080754] gil20587441gbIB07854.11B07854 [2058744] gil2l97119|gb|AF003921.1|AF003921 [2197119] gil20587431gbIB07853.11B07853 [2058743] gil2982722ldbjlAB012213.11AB012213 [2982722] gil20587421gbIB07852.11B07852 [2058742] gil2982721IdbjIAB012212.1|AB012212 [2982721] gil205874ligbIB07851.11B07851 [2058741] gil2058780|gbIB07890.11B07890 [2058780] gil2058740igbIB07850.11B07850 [2058740] gil2058779igbIB07889.1|B07889 [2058779] gil29475271gbIT25933.1 T25933 [2947527] gil20587781gbIB07888.11B07888 [2058778] gi129243021embIX81655.11EHERMAM [2924302] gil20587771gbIB07887.11B07887 [2058777] gil2664256lembI2234.11EFAS48C [2664256] gil2058776|gbIB07886.1|B07886 [2058776] gil2879906ldbj1D85752.11D85752 [2879906] gil2058775|gbIB07885.11B07885 [2058775] gil27462161gblAF028836.11AF028836 [2746216] gil20587741gbIB07884.1|B07884 [2058774] gil27458251gblAF039139.11AF039139 [2745825] gil2058773|gbIB07873.1|B07873 [2058773] gil2696019ldbjlAB007844.11AB007844 [2696019] gil20587721gbIB07872.11B07872 [2058772] gil48999lembIX62280.11EHPBP5G [48999] gil20587711gbIB07871.11B07871 [2058771] gil26544771gbIU89914.11BFU89914 [2654477] gil2058770|gbIB07870.11B07870 [2058770] gi1433471emb1X68646.1IEHPSRAA [43347] gil2058769igbIB07869.11B07869 [2058769] gil26130341gbIAH005624.11SEQEDDH4RR gil20587681gbIB07868.1|B07868 [2058768] [2613034] gil20587671gbIB07867.11B07867 [2058767] gil20587661gbIB07866.11B07866 [2058766] gil26130321gblAF029774.11EDDH41 [2613032] gil2058765|gbIB07865.1|B07865 [2058765] gi12613031 gbIAHOOS623.1 SEGEDDHIRR gij25875~gbB0765.[2613031] gil20587641gbIB07864.11B07864 [2058764] gij26130301gb1AF029773.11EDDHIRR2 [2613030] gig2058763igb2B07883.1iB27883 [2058763] WO 00/32825 PCT/IB99/02040 345 gil2613029|gblAF029772.1|EDDHIRR1 [2613029] gi122319921gbIU94530. 1 1EFU94530 [2231992] gil26130281gbIAH005622.1[SEG_EDH19RR gil2231990 gbIU94529.11EFU94529 [2231990] [2613028] gil22319881gb1U94528.11EFU94528 [2231988] gil26130271gblAF029771.1IEDH19RR2 [2613027] gil22319861gbIU94527.IIEFU94527 [2231986] gil2613026|gblAF029770.IIEDH19RR1 [2613026] gil22319841gbjU94526.11EFU94526 [2231984] gil2613025|gblAH00562.1ISEGEDISRR gil22319821gbIU94525.I ECU94525 [2231982] [2613025] gil26130241gblAF029769.1|EDISRR2 [2613024] gij22319801gbIU94524.11ECU94524 [2231980] gil2613023|gblAF029768.1|EDISRR1 [2613023] gil22319781gbIU94523.I ECU94523 [2231978] gil1881226[dbjlAB001488.11AB001488 [1881226] gil223I9761gbIU94522.11ECU94522 [2231976] gi[254716OIgblAF023104.1|AF023104 [2547160] gil223I9741gbIU9452 1.1 IECU94521 [2231974] gil2547159|gbIAFO23103.11AF023103 [2547159] gij21966851gbjU25090.1IEFU25O9O [2196685] gil2547158|gblAF023102.11AF023102 [2547158] gil2197120lgblAF003922.11AF003922 [2197120] gil2547157|gblAF023101.1|AF023101 [2547157] gil21966831gbIU25095.1IEFU25O95 [2196683] gil2415383|gblAF015775.I AF015775 [2415383] giJ2196681 1gbU25094. 1 jEFU25094 [2196681] gil23886361gblU94356. 1EFU94356 [2388636] gil2I966791gbIU25093.11EFU25093 [2196679] gil2388634|gbIU94355.11ECU94355 [2388634] gil21966771gbjU25092.1jEFU25O92 [2196677] gil2340825ldbjjD26045.I|D26045 [2340825] gil21966751gbIU25091.1IEFU25O91 [2196675] gil2226147|emblY14080.1|BSY14080 [2226147] gil21966731gbjU24682. IEFU24682 [2196673] gil23270261gbIU87997.l1EFU87997 [2327026] gil5325331gbIU09422.11EFU09422 [532533] gil2318058|gblAF012532.11AF012532 [2318058] gil4872711dbiD17462.1IENENTP [487271] gi|1848175lemblX87189.1IEM23S5SSP [1848175] gil468459ldbjlD28859.1IENEPPD1 [468459] gil1848174lembIX87187.1|EM16S23SS [1848174] gil440135ldbjID16334.1lENEATPK [440135] gil1848173|emb1X87188.lIEM16S23SP [1848173] gil39l68OldbjlD13816.1 ENENAABS [391680] gil1848172lemblX87185.1IEH23S5SSP [1848172] gil1402524idbjjD78257.1 D78257 [1402524] gil1848171lembIX87184.1IEH16S23SS [1848171] gil709995ldbjID30808.11BACYCB20 [709995] gil1848170emblX87181.1IEF23S5SSP [1848170] gij2l192651gbIU91527.11EFU9I527 [2109265] gil1848169lembIX87183.11EF23S5SPA [1848169] gill04lll2ldbID78016.1IENEPPDIA [1041112] gil 1848168lemblX87191.IIEF23S5SAC [1848168] gil1339880ldbjlD85392.11ENERPA [13398801 gil1848167lemblX87180.1[EF16S23SS [1848167] gil1339878ldbjlD85393.I1ENEGEIE [1339878] gill848166lemblX87182.1IEF16S23SP [1848166] gil662918fembjZ468O7. 1 IEHCOPAYZ [662918] gill848165lemb|X87190.1IEF16S23SC [1848165] gil769796lembIX86176.1IEFRPODDNE [769796] gill848164lemb1X87186.1IEF16S23SA [1848164] gill8546381gbIU51479.1IEGU51479 [1854638] gil1848156lemblX87179.1IED23S5SSP [1848156] gil 8572211gbIU72706.1 EFU72706 [1857221] gil1848155lemblX87178.1|ED16S23SS [1848155] gi118572191gbIU72704.11EFU72704 [1857219] gil1848154lemblX87177.1 ED16S23SA [1848154] gil18572171gb U72705.I1ECU72705 [1857217] gil2274942|emblAJ000346.11EHNAPBC [2274942] gil1272655lembIX96978.1IEFPPD1GN811272655] gil2274939lemblAJ000042.1 |EFGLS24B gill272652lemblX96976.IIEFPLSEPI G [1272652] [2274939] gi1l279406lembIX96977.11EFPAD1ORF gil4l4575|gb|L12710.1IENEAAC [414575] [1279406] gii22456031gblAF006008. I 1AF006008 [22456031 gil 1070149lemblX932 1.1 EFTNFO 1 [1070149] WO 00/32825 PCT/IB99/02040 346 gil1065723lembjX92947. 1IEFTETMGN [1065723] gil14693411gbIU30931.11ESU30931 [1469341] gil1019639lgbjL38972.1|PH4COINJN [1019639] gil4883311gblM77276.1ISYNGIP2122 [4883311 gil1151151|gb[U43087.1|EFU43087 [1151151] gilI0461771gblU39733.11 [1046177] gil1098507|gbjU17283.1IBMJ17283 [1098507] gij 2366131gbIU49939.I CVU49939 [1236613] gil14980721gblU64887.I|EFU64887 [1498072] gil47491lembIX55766.1ISS16SR5G [47491] gil1498071|gbIU64886.IjEFU64886 [1498071] gi147490IembIX55767.1ISS16SR3G [47490] gil1469783|gbIU58049.11EHU58049 [1469783] gil47061lemblX56353.I SFTET916 [47061] gil17636661gb[U81452.1|EFU81452 [1763666] gil49022lembIX62755.1ISFNPRG [49022] gil624694|gbIL38973.1IPH4SEQ [624694] gil47047lembIXl7214.11SFPASA1 [47047] gill730458lemblZ83305.1IEFVANRES [1730458] gil47044embjX68847.1ISFNOXAA [47044] gil1419498lembIX84796.11ECPFW4 [1419498] gil47O33lembIV0l547.1ISFKANR [47033] gi[1419497lemblX84795.IIECPFW3 [1419497] gil47Ol8lemblX02027.1ISF5SRNA [47018] gil1419496lemblX84794.1|ECPFW1 [1419496] gilS l144lemblX75752. 1 IMP I6SRNAO [511044] gil254400|gblS43266. 1|S43266 [254400] gil511043 lemblX7575 1.1 IMP 1 6SR243 [511043] gil239025|gblS66277.l1S66277 [239025] gil886481lemblX82819.1IESPLPAM [886481] gil10549311gblU38590.IlEFU38590 [1054931] gij5173871emblX76177.I ES16SRR [517387] gil1244573|gbIU39788.1|EHU39788 [1244573] gil472916lemblX76913.1 IEHNTPOP [472916] gil1244571|gblU39789.11EGU39789 [1244571] giJ4335 1 lembIXSS133. ES 16SRRN [43351] gil1244569|gbIU39790.11EFU39790 [1244569] gill 143442lemblX92687. 1 IEFPBP5G [1143442] gil1255020lgblU39777.11ESU39777 [1255020] gil963O32lembIZ5O854.1IEHARPQTOU [963032] gil1255018|gblU39775.1 EPU39775 [1255018] gil886479lembIX84818.1IEHDNAPSR [886479] gil12550161gblU39778.11EDU39778 [1255016] gil551437lemblX81654.1IEHIS12I6 [551437] gil1255014|gblU39776.1ECU39776 [1255014] gil467805lembIX78425.1IEFPBP5 [467805] gil12550121gb|U39774.11EAU39774 [1255012] gil29672IlemblX55961.1IEFPD78 [296721] gi|1619922|gblU69267. 111VU69267 [1619922] gil287946lemblZl9137.1IEFPTSHGN [287946] gil790436lemblX84861.1IEFEFMPBP5 [790436] gil49O42lembIX63285.11EHNAKA [49042] gil790434lembX84858.IIEFD63RPSR [790434] gil49O19lemblX62658.1IEFSEA1 [49019] gil790432lemb|X84862.11EF721PBP5 [790432] gil43337lemblZl2296.1IEFSPREG [43337] gil790430lemblX84860.1IEF63RPBP5 [790430] gi143335lemblX56895.IIEFPVANAG [43335] gil790428lemblX84859.1IEF366PBP5 [790428] gil43333lembIX16421.1IEFPF54 [43333] gill572800lgblU70854.IICELF38A5 [1572800] gil43331 emb1X62657.1IEFORF3 [43331] gil10418161gbJU17153.1IEFU17153 [1041816] gil 1065721 lemblX92945. 1 JEFCAT501 [1065721] gil1086523|gblU39859.11EFU39859 [1086523] gil806551lemblZ49243.1IEF4110SOD [806551] gil403564|gblU01917.1IEFU01917 [403564] gil806549lembIZ49244. 1 IEF4105SOD [806549] gil 1515474|gblU66286. 1EFU66286 [1515474] gil5O5530lembIX79542.1IEFAS48 [505530] gill513O68|gblU15554.1ILMUI5554 [1513068] gil43323lembIX62656.1IEFASPI-[43323}- gil 1296520lemblX94181.1 |EFENTAORF gil4O840lembIX56422. 1 lEG 1 6SRNAG [40840] [1296520] gil48189lembIX04388.1ITN1545rR [48189] gil14880691gblU63997.1|EFU63997 [1488069] gil9288141gbIL40841.11ENETRANSPO [928814] gil2095251gbU35369.11EFU35369 [1209525] gil141856gbl0794.1ADUREPABC [141856] WO 00/32825 PCT/IB99/02040 347 gil149125[gbIM90647.1|IP8VANY [149125] gil153852lgbIAH0O0939.1ISEGSTRTN916 gil1418621gb|M87836.1IAD1TRAE1 [141862] [153852] gil141860igbIM84374.1IAD1TRAA [141860] gil 538511gbIM22645.11STRTN9162 [153851] gi1141853|gblM62888.1IAD1PAD1 [141853] gill538501gbIM20864.1ISTRTN9161 [153850] gil1101637ldbjlD31674.1IEVM16RNA7 [1101637] gi115366OjgbIM36878.11STRIF2BA [153660] gil1101636ldbjlD31675.IIENE16RNA8 [1101636] gi11535851gbIM13771.IISTRBRP [153585] gil497792ldbjID31676.1IENC16RNA9 [497792] gi11535751gbIM64265.IISTRATPEFHA [1535751 gil1022729|gblU36195.1IEFU36195 [1022729] gil1535651gbIM90060.11STRATPASEA [153565] gil488338|gblM77279.1|SYNGIP3124 [488338] gill529691gbIM92376.1ISTABLAIA [152969] gil488335|gblM77278.1ISYNGIP2563 [488335] gil309660igbIL14285.IIPCFPRGWZY [309660] gil488333|gb[M77277.1ISYNGIP2124 [488333] gil4337141gblL120331lENESATA [433714] gil488329|gblM77275.IISYNGIP2121 [488329] gil29O6451gbILlS3O4.1IENEVANB2A [290645] gil388267|gblL19532.1|AD1TRAC [388267] gil1483311gbIM84146.11ENEVANR [148331] gil493016|gblU03756.11EFU03756 [493016] gil1483291gbIM64304.1IENEVANH [148329] gil4535361gblL28754. 1INSTRAN [453536] gill483261gbIM68910.11ENEVANCRES [148326] gil1536581gblM58002.1ISTRHYDROLA [153658] gi11483241gbIM7513211ENEVANC [1483241 gil475427|gblU0068 1.1 |EFU00681 [475427] gil1483231gbIL06138.1IENEVANB [148323] gil8187041gblU24692.1EFU24692 [818704] gil1483211gblM85225.1IENETETM [148321] gil155036|gblM97297.1|TRNVAN [155036] gil148320lgbIL00925.11ENERTRNA [148320] gil1505521gbIM64978.1IPCFPRGAB [150552] gij 483191gbIL00924.IIENERRNA [148319] gil786274|gblU22541.11EHU22541 [786274] gi11483171gbIM81466.11ENERECA [148317] gil786273|gblU22540.11EHU22540 [786273] gil1483151gbIM81961.1IENENAPA [148315] gil559858|gb|L37110.1|AD ICLYL [559858] gil1483121gbIM38386.1IENEMSPDPS [148312] gil6436141gblU16659.1[ECU16659 [643614] gil1483lOlgbIM37I85.11ENEGELE [1483101 gil6436121gblU16658.1[ECU16658 [643612] gil148307igbIL07892.11ENEBLACREG [148307] gil290641|gblL13292.1|ENECOPPUMP [290641] gil1483051gblM60253.1IENEBELAA [148305] gil624701|gb|L29639.1|ENEVANCRF [624701] gil1483031gbIM77639.11ENEB14NAM [148303] gil624699|gb|L29638. 1 IENEVANCR [624699] gil29O6441gbIL 16515.1 IENERGTG [290644] gil6246921gblL29641.1|ENEDDLA [624692] gill 549541gbIM37184.1ITRN916 [154954] gil6246901gblL29640. 1[ ENEDDL [624690] gil1483011gbIM69221.11ENEAAD9A [148301] gil4930941gbIL328 13.1 IENERRD [4930941 gil148308gblM38052.1|ENECYLB [148308] WO 00/32825 PCT/IB99/02040 348 Table 28 Phage Dp1 complete genome sequence. 56506 nucleotides. 1 ataataaaaa tatgaagcag atattgggtt aattattgct taacaaaatg caccgaattt gtgtataata 71 taagtgaagc agttttgtaa acctgacatc ctgctaaata aaaataaagg aggctcgaac atgagtcaaa 141 acactacacg cactgacgCt gaattgacag gcgttactct tttaggaaac caagacacca aatacgatta 211 tgactataat ccagacgtcc ttgaaacttt ccctaacaaa catcctgaaa ataattacct agtaacattt 281 gacggatatg aattcacttc cctttgccct aaaacaggac agcctgactt cgcgaatgtt ttcattagtt 351 acattccaaa cgaaaagatg gttgaatcta aatcattgaa attgtactta ttcagtttcc gtaaccacgg 421 tgacttccac gaagattgca tgaacattat tttgaatgac ttgtatgaat tgatggaacc taagtacatt 491 gaagtcatgg gcctattcac tcctcgtggt ggaatttcaa tttacccatt cgtcaacaaa gtgaatcctc 561 aatttgcaac tcctgaactt gaacagcttc aacttcaacg caaattgaac ttccttggaa atgttcaagg 631 tcttggacga gctattcgat aggaggctgg aatgaaatca gtagttttat tatccggcgg agtcgactca 701 gccacttgtt tagcaattga agttgacaag tggggttcta aaaatgttca tgctatagca ttcaattacg 771 gacaaaagca tgaagcagaa cttgaaaatg ctgctaatgt tgcaatgttc tacggagtca agttcaccat 841 tcttgaaatt gactcgaaaa tctactcaag ctctagctct tccttattac aaggaaaagg cgaaatttca 911 catggaaaat cttacgctga aatcctagca gagaaggaag tagttgacac ctatgttcca tttagaaatg 981 gactaatgct ttcacaggct gcggcttatg cttattcggt tggagcttct tacgtcgtat atggtgctca 1051 cgcagacgat gcggctggag gtgcttaccc tgattgcact cctgagttct ataattcaat gtcaaatgca 1121 atggaatatg gaactggagg caaggtaacc cttgtcgctc ctctacttac tctaaccaag gcgcaagtcg 1191 ttaaatgggg aattgattta gatgttcctt atttcttgac tcgttcatgt tatgaaagtg acgctgaaag 1261 ttgtggaact tgcgcaactt gtatcgaccg caaaaaggca ttcgaagaaa atggaatgac tgaccctatt 1331 cattataagg agaattgata tgagagtttc taaaacctta acattcgacg cagctcatca actagttgga 1401 cattttggaa aatgcgcaaa tttgcacggg catacttaca aagtcgaaat ttcattagca ggcggaactt 1471 atgaccacgg ttcgagtcaa gggatggttg ttgactttta tcacgtcaag aaaatcgcag gtacattcat 1541 tgacagactt gaccacgctg ttcttcttca agggaatgaa ccaatcgctt tagcaaatgc agttgacacc 1611 aagcgagttc tatttggatt tagaactacg gctgagaata tgtcaagatt ccttacctgg actctcacgg 1681 agcttatgtg gaagcatgct cgtatcgact ctatcaaact atgggaaact cctacaggtt gcgcagaatg 1751 tacttactac gagattttca cagaagacga gattgaaatg ttcaagaacg taacctttat cgacaaagac 1821 gaaaagatta ctgtccgcga aattttagag caggagcagg ataatggtta atcaatacaa tcagcctgaa 1891 agaggcaaga ttcgaatcaa tgttcgcgac cctgagaaaa tgcctatcat ggaaattttc ggtcctacaa 1961 ttcaaggtga aggaatggtt ataggtcaaa agactatttt cattcgaact ggtggatgcg actatcattg 2031 caactggtgt gactcagcct ttacctggaa cggtactact gagccggaat atatcacagg caaagaagct 2101 gctagtcgaa tcttgaaact agctttcaat gataaaggtg aacagatttg taaccacgtg acattgactg 2171 gaggaaatcc tgccttaatc aacgagccta tggctaagat gatttcgatt ctaaaagaac atggattcaa 2241 gtttggtctc gaaactcaag gaactcgatt ccaagaatgg tteaaagaag taagcgatat cactattagt 2311 cctaaaccgc cttcaagtgg aatgagaact aatatgaaaa ttcttgaagc tattgtagat agaatgaatg 2381 atgaaaacct tgactggtca tttaaaatcg ttatctttga cgaaaatgac ctagcttatg cgcgtgatat 2451 gtttaaaact ttcgaaggca agttacgtcc agtgaactac ctttcagttg ggaatgcaaa cgcatacgaa 2521 gaaggaaaaa tcagtgatag gcttcttgaa aagttgggat ggctttggga taaagtgtat gaagacccag 2591 ctttcaacaa tgttcgacct ttaccgcaac ttcatacact tgtttatgat aataaaagag gagtataaaa 2661 tgaaaattga gcatctagat aaaatcggta acgtattagg gagagagaac ggatgggctt cccttaagcc 2731 ggatgaaatt gtaaccttgg acaatactga ggcagccgtt caaagacttt ttggtctatt aggcgaggac 2801 gcagaacgtg acgggttgca agatactcca ttccgttttg ttaaagcact Cgctgaacat accgtagggt 2871 atcgagaaga ccctaaactt catctcgaaa aaacattcga cgtcgaccat gaagaccttg ttcttgtgaa 2941 agacattcca ttcaattctt tatgtgagca tcatttagct ccgttcgtag ggaaggtgca tattgcatac 3011 attcctaagg ataagattac aggtctttca aaattcggtc gagtggttga aggatacgct aaacgacttc 3081 aagtacaaga gcgcttgact caacaaatcg ctgacgctat tcaggaagtt ctaaatcctc aagcagttgc 3151 ggtcatcgta gaggctgagc atacttgcat gagcggacgc ggtattaaga agcacggggc aacgacagtg 3221 acttcaacta tgcgaggtct tttccaagat gacgcatctg ctcgagcaga attgcttcag ttgattaaaa 3291 agtaggaggc ggaaaatgaa taaaagtgca accttttggc ttgttcgaac agctcttatt gcggctctat 3361 atgtgacatt gaccgttgca ttttctgcta ttagttatgg acctattcaa tttagagtca gtgaagcctt 3431 gattcttcta cctttatgga accatagatg gactccgggg attgtattag gaacaattat tgcaaacttc 3501 ttttcacctc ttggactgat tgacgtttta ttcggttcac ttgctacctt ccttggagta gtggcaatgg 3571 tgaaagttgc taagatggca agtcctctat attcacttat ctgtccagtt cttgctaatg cttaccttat 3641 tgcgctggaa cttcgaatag tttactcttt acctttttgg gaatctgtca tctatgtagg aattagtgaa 3711 gcgattatcg ttttaatttc atacttcctt atttccacgc tggcgaagaa caatcatttt agaacactga 3781 taggagcgaa aaatgggatt taatctatac ttcgcaggag gtcacgctat tagcactgac gattatttga 3851 aggaaagagg agccaatcgc ctattcaatc aactgtacga aagaaacggg attggcaaaa ggtggattga 3921 gcataagaaa accaatcCaa gcactacttC aaaactattc gtcgactcta gtgcatattc tgctcatacc 3991 aaaggggctg aagttgacat tgacgcctat atcgaatacg tgaatgaaa cgtgggaatg tttgactgta 4061 tcgccgaact cgataaaatt cctggtgtat ttagacagcc taagacacgt gaacagcttt tggaagcacc 4131 acaaatttct tgggataatt atctatacat gcgcgagcga atggttgaga aagacaagct cttacctatt 4201 ttccatatgg gagaagactt taaatggctc aacttgatgc tcgaaactac attcgaaggc ggaaagcaa 4271 ttccttacat tggaatttca ccagccaatg actcgactac gaagcataaa gacaagtgga tggaaagagt 4341 attcgaagtt attcgaaaca gttctaatcc agacgttaag actcacgcat ttgggatgac agttactagc 4411 caattagagc gtcacccatt ctatagcgcc gactctactt Ctgtactgct cacaggagcg atgggaaaca 4481 ttatgacgtc aaaaggatta gttgacttgt cacagaagaa tggaggaatt gatgctgtcc gtaggctgcc 4551 aaaaccggtt caagttgaaa ttgaatccat tatcgaagaa actggagcgc attttagcct agagcaatta 4621 gttgaggact ataaacttcg agcattgttc aatgttcaat acatgctgaa ttgggcagag aactatgaat 4691 tcaagggaat taaaaatcgt caacgtcgac tattttagat aagagctttt cgctcttatt ttttttaaaa WO 00/32825 PCT/IB99/02040 349 4761 aaaaatgaac tttttataca aaaacgcttg actttattca ctcattatcg tataatcata atataaataa 4831 aacgaataag aggtaaataa aatgacagca gttcaacaag ttaagttcta cttagaagaa gccggcgctc 4901 actttctaaa agatgttgag tacagtgaca acttagagca agcaattatg aaagatattc tiaaatggaa 4971 tggcgctcat agagatgagc acgatatgaa aataacttca tacgaagtat tatagagagg ggtaaggcta 5041 tgaaaaaagt tcaaacttat caagaatatc taaaactagt tgagttcaaa cgtcaacttt ctttaaatct 5111 tcgagaagga aaaataggag tCgatgaagc ggttattcaa ttattcacct tctatagttt caacaatatc 5181 gaggaacctc ctttcattgt actcaaaatg caagaggctg ccgtgaacgg gacttatgaa gcaaaactca 5251 atatgcttaa aagatttaaa attatttaga aacggcttta caaactcgcg ataattcgtg tatattatat 5321 atatcaaaaa aaggaggctc atattatgag tattaagttc aaaaccgaag aactttcaaa aattgtttct 5391 cagctcaata agttgaagcc tagcaagttg ctagaaatca caaactattg gcatattttt ggtgacggcg 5461 aatgcgtcat gtttacagcg tatgatggct caaacttcct tcgatgcatt atcgacagcg atgttgaaat 5531 tgacgtgatt gtgaaagcag agcagtttgg aaaacttgta gaaaagacca cggccgcaac cgtcacatta 5601 gttcctgaag aatcttcgct aaaagttatt gggaatggtg agtacaatat tgatattgtt acagaagatg 5671 aagagtaccc tacattCgac cacttgctcg aagacgtgag tgaagaaaat gctctcactt tgaaaagctc 5741 gctgttctac ggaatcgcca atatcaacga ttctgcggta tctaaatcag gagcagatog aatttatacc 5811 ggcttcctgt taaaaggcgg aaaagcaatt actacagaca tcattcgcgt atgtatcaac cctatcaagg 5881 aaaagggact agaaatgctc attccttaca acctaatgag tattttagca agtattcctg atgagaagat 5951 gtacttctgg caaattgacg atactactgt ctatatttca tcggcttcag tcgaaattta tggaaaattg 6021 atggaaggta tggaagatta tgaagacgtt tcacagcttg actcaattga gtttgaagat gatgcggcta 6091 tccctacagc agaaatcctg agcgtattag accgccttgt actattcact tcagcctttg acaaaggaac 6161 cgtcgaattc ttattcttga aagaccgact tcgaattaaa acttctacta gcagttatga agacatcatg 6231 tacgcatctg ctggcaagaa agtttcgaag aaagaattca cttgccacct taacagctta ctcttgaagg 6301 aaattgtatc aaccgtcacc gaagaaaact tcactgtctc ttatggaagc gaaaccgcaa ttaagatttc 6371 atcgaatggt gtcgtttact tcctagcact tcaagagccg gaagaataat ggccaagtcc aatttaacta 6441 gaattgcaaa gatggttaga gcaggaaaca gtgaaggtcc tgcttcatct tttgtcaatt cgctgacccg 6511 ggttattgaa cgaactcagc ctgaatataa tccttcgaca tattataagc ccagcggggt tggtggatgt 6581 attcgaaaaa tgtatttcga aagaatcggt gagtctatta tagataacgc agattctaac ctaattgcaa 6651 tgggcgaagc tggaacattt aggcacgaag ttctccaaga gtacatggtt aaaatggctg aaatcgatga 6721 ggactttgaa tggttgaatg tagcagagtt cttgaaagaa aatccagttg aaggaactat cgtcgacgag 6791 cgtttcaaga aaaacgatta tgaaacgaag tgtaagaacg aacttcttca actttcattc ttgtgtgacg 6861 gactagttcg atataaaggc aagctctaca ttttagagat taagactgaa accatgttca agttcactaa 6931 acatactgag ccctatgaag aacacaagat gcaagcaact tgctacggaa tgtgtctagg agtcgatgat 7001 gtcattttcc tttatgaaaa tcgagataac ttcgaaaaga aagcctacac gtttcacatc acagacgaga 7071 tgaaaaatca agtccttgga aaaattatga cctgcgaaga gtatgtagag aaaggcgaaa gtcctaaaat 7141 ctattgctct tcagcctatt gcccatattg tagaaaggaa ggtcgaaatc tgtgagctat actggaaaaa 7211 tgttcgagga agactttttc gaaggtgcaa aagactttga gaaagatgct ttcacggtcc gtctatatga 7281 taccactaat ggatttcgag gagttgcaaa tccctgcgat tatatagccg caactaactt tgggaccttg 7351 tttattgaac tgaaaactac taaagaagct tctttgagct ttaataacat cactgataat caatggttcc 7421 agctatcacg cgcagatgga tgcaaattta ttctcgccgg aattttagtg tatttccaaa agcatgaaaa 7491 gattatatgg tatccaattt caagccttga aaaaattaaa cggtctggag ttaaaagcgt caacccaaac 7561 ttcatcgatg cagggtatga agtttcttac aagaagcgtc gaactagatt gaccattcct ttccaaaatg 7631 ttctagatgc agttgagctt cattacaagg agaaaagcaa tggcaagacc taagttacct caaattgata 7701 ttcgagaaga agaaatacga gatgctcaag acgtagcaga ctcgtatggt gcgattatca ataaagtagt 7771 cgacgaaatt gttgaagcag cttgcggttc acttgaccag gcaatggaag aaattcaaat agttgtaagc 7841 caaaatcctg tcattatgga agaccttaac tactacattg gctatcttcc cactcttctt tatttcgccg 7911 cagatagggc ggaaatggtg ggaatacaaa tggattcaag ttctgctatc aggaaagaaa aatacgataa 7981 tctatacatt ttagccgccg ggaaaactat tcctgacaag caagcagaaa ctcgaaaac tgtcatgaat 8051 gaagaagtca tcgaaaatgc ttacaagcga gcctacaaga aagttcaatt aaagctagaa caggccgata 8121 aggtattagc atctttaaaa cgaattcaaa cctggcaact agcagagtta gaaactcagt caaataattc 8191 aaaaggagta ttattaaatg caaaaagacg tagacgtgaa aatgattgac cctaaacttg accgattaaa 8261 atacacaggt gattgggttg atgtacgaat tagttctatc actaaaattg acgccgacag cgccgatgtc 8331 tcaagatgtc gaaaagtgct tcaaaaggct caagtatatt cagtggcggc aggtgaatgc attaaaattg 8401 cacacggatt tgctcttgaa cttcctaagg gatatgaagc aatcttgcat cctcgttcca gtctttttaa 8471. gaaaactggt ctaatcttcg tttctagcgg agtgattgac gaaggttaca aaggtgacac tgatgaatgg 8541 ttctcagttt ggtatgctac tcgtgacgca gatatcttct acgaccaaag aattgcccaa tttagaattc 8611 aggaaaagca acctgctatc aagttcaatt tcgtagaatc tttaggaaat gcggctcgtg gaggccatgg 8681 aagtacaggt gatttctaat gaaattggaa cagttgatga aggactggaa taaggattcg aaagctcttg 8751 tagcagttca aggacttgaa cgtgaagcgc ttccaagaat ccctttttct gcgccttcta tgaattatca 8821 aacctacggc gggctccctc gaaaaagggt agttgaattc ttcggtcctg agtcaagtgg gaaaactact 8891 tcagctctcg acattgtcaa gaatgcgcaa atggtatttg agcaggaatg ggaacagaag actgaagaac 8961 tcaaggaaaa gctggaaaat gcgcgtgcat ccaaagctag caagactgct gtcaaggaac ttgaaatgca 9031 actcgatagt cttcaagagc ctcttaagat tgtatatctt gaccttgaga atacattaga cactgagtgg 9101 gctaaaaaga ttggagtcga tgttgacaat atttggatag ttcgccctga aatgaacagc gctgaagaaa 9171 tacttcaata tgttttagac attttcgaaa caggtgaagt tggcctagta gttctagatt ccttgcctta 9241 catggtcagt caaaacctta ttgatgaaga gttgactaaa aaggcctatg caggaatctc agcgcctttg 9311 actgaattta gtcgaaaggt tactcctctt cttactcgct acaatgcaat attcctaggc atcaatcaaa 9381 ttcgagaaga tatgaatagt cagtacaatg cctattcaac tccaggcgga aagatgtgga agcatgcttg 9451 tgcagttcga cttaaattta gaaaaggtga ctaccttgac gaaaacggtg catcattgac ccgtactgct 9521 cgaaaccctg cagggaatgt agtagagtca ttcgtcgaga agaccaaagc atttaagccg gaeagaaaat 9591 tagtttccta tacgctttcc tatcatgatg gaattcaaat tgaaaatgac cttgtagatg tcgctgtcga 9661 atttggagtc attcaaaagg caggggcatg gttcagtatc gtcgaccttg aaactggaga aattatgaca 9731 gatgaagacg aagaaccatt gaagttccaa ggcaaggcaa atctagttcg acgcttcaag gaggatgact 9801 acttattcga catggtgatg actgcggttc acgaaattat cactcgagaa gaaggctaat gcaaaaatct 9871 ctatttggac ctaagctagt gcctgctagt tcaaggcgca agaaaagaac ggttccaaaa cctaaaccta 9941 aaatcgatga gcaagtggtt gagcttatga accgcagaga gcgtcaagtg cttgttcata gttgcatcta 10011 ttattatttt aatgactcaa ttatagcaga cgggcagtat gacaaatgga gccacgaac atattctctt WO 00/32825 PCT/IB99/02040 350 10081 atagtttcgc accctgatga gtttcgacag actgttctct ataacgagtt taaacagttt gacggaaata 10151 ctggaatggg tcttccatac gactgtcagt ttgctgtaag ggtcgcagaa aggcttttaa gaaaatgaat 10221 ttagcttcta aataccgtcc tcaaactttc gaggaagtgg tagctcaaga atatgtcaaa gaaattcttt 10291 tgaatcaatt acaaaatggc gctatcaaac acggctatct attctgtggt ggcgctggaa ctggtaaaac 10361 cactactgct cgaattttcg cgaaggatgt gaacaaagga cttggctctc ctattgaaat tgatgctgct 10431 tctaataatg gggtagaaaa tgttcgaaac attattgaag attctagata caagtctatg gacagcgagt 10501 tcaaagttta catcattgac gaggttcata tgctttcaac cggagcattt aatgcgctgt tgaaaacatt 10571 agaagagccc tcatcgggaa ccgtgttcat tctatgtact actgaccctc aaaagattcc tgacactatt 10641 ctcagtcgag ttcaacggtt tgactttact cgaattgata atgacgacat cgttaatcaa cttcaattta 10711 ttatcgaaag tgaaaatgaa gaaggagctg gttatagtta tgagcgtgac gccctttcgt ttattgggaa 10781 acttgcaaat ggaggaatgc gtgacagtat cacaaggctc gaaaaagtcc ttgattatag tcatcacgtt 10851 gacatggaag ccgtttctaa tgcactagga gttccggact acgaaacatt cgcttcactt gttgaagcta 10921 ttgccaacta tgacggctca aagtgtttag aaattgtaaa tgacttccac tactcaggaa aagacttgaa 10991 attagtgact cgaaacttta cagacttcct tttagaggtt tgtaagtatt ggctagttcg agatatttca 11061 atcactcaac ttcctgctca ttttgaaagt aagctagagc aattctgtga ggcttttcaa tatcctactc 11131 tattgtggat gctagaagaa atgaatgaac ttgctggagt tgttaaatgg gagcctaatg ctaaaccgat 11201 aattgaaacc aaacttcttt tgatgagcaa ggaggagtga catgattgga cagggacttg ttaaatctac 11271 catttcgaaa tggaaacaac ttccaaaata tataatcgtc gaaggtgaag taggttcagg acggaagacc 11341 ttaatccgtt atattgcttc gaaatttgac gctgattcta ttgtagtagg aacgagtgta gatgacattc 11411 gaaacatcat tcaggatgca cagactattt tcaaggcgag aatctacgtg atagacggaa atagcctgtc 11481 aatgtcagct cttaactcgc ttttgaagat agcggaagag ccacctttaa actgtcatat agccatgact 11551 gttgatagca tcaataatgc tttacctacg cttgcaagta gagcaaaagt tctaaccatg ctaccttata 11621 ctaatgaaga gaaaatgcag tttgtcaagt cctacaagaa ggtagatact tcaggaattg acgaccgagc 11691 gattgtagac tattgcaatc ttgccagcaa tcttcaaatg cttgaagaca tattagaata tggcgcagaa 11761 gagctatttg aaaaggttac aacattttat gacttaatat gggaggcaag tgctagcaat tcgctaaagg 11831 ttactaattg gctcaaattt aaggaaactg atgaaggaaa aattgagcct aaacttttcc tcaactgtct 11901 tttaaattgg tcgacagttg tcatcaggaa gcactatgta gaaatgtctt tcgaagaact tgaggcccat 11971 gaccttttag tgagggaagc atctaggtgt ttgcgaaagg tatctaaaaa gggctcaaat gcgcgtgtct 12041 gcgtgaacga atttatcagg agggtcaaac aagttgagtg atttagtatc atttcaaaaa gacattcgaa 12111 ccaataatct aaagccgttc tatatcttgt acggcgaaga aattggtctt atgaatgttt atctcaatca 12181 aatgggaaat gtagttcgag aaacttcggt ttcaacagtc tggaaaaccc tcactcaaaa agggctcgtt 12251 tctaatcatc gaatattcgc tgttcgagat gataaggagt ttctgtctaa tgagtcgagg tggaaaaggc 12321 ttccggatgt tagatatggg acacttgttt tgatggttac taaaattgac aagcgaagca agttgctaaa 12391 ggcctttcct gataattgtg ttgagtttga gaaaatgact gacgcgcagt tgaaaaggca ttttgtgtct 12461 aaatactcga ctattgatag cgacatgatt gacatggtta tccagttctg tctaaacgat tactctagaa 12531 ttgacaatga attggacaag ctgtcgcgat tgaaaaaggt tgacgcatca gtagttgaat ccattgtcaa 12601 gcacaagacc gaaattgaca ttttcagcct agttgatgat gtattggaat ataggccgga gcaggcaatt 12671 atgaaagtga ctgaactttt agccaaagga gaaagtccta ttggattgct taccttgctt tatcaaaatt 12741 ttaataacgc ttgtcttgtg ctaggagccg atgagcctaa agaagccaat ctaggcatta agcagttctt 12811 aatcaataag attgtctata actttcaata cgagcggac tcagcctttg aaggcatggc tattttaggt 12881 caagctatcg agggcataaa gaatggtcgc tatacagaaa gttcagtggt ctatatttct ttgtataaaa 12951 ttttttcact tacttaacaa ataagctgaa atctgtgtat attacagtat aagcaaagga ggacagccta 13021 tgacagaagt tgcggtaaat agcccgcaaa aggtgagagt agttatggtc gggaatattg aatttctcga 13091 atatttaaaa aggaagtacg gaacagaaac ttccatcagt tatattatag aaaatgaaag gggtctaata 13161 tgacagactt taaaaaacgc ttcaagaaag cagtaacaga aacaatcaat cgtgacggta tcgagaacct 13231 tatggattgg ctcgaaaatg ataccaattt cttctcaagt ccagcaagca ctcgatacca tggaagctat 13301 gaaggtggac ttgtcgagca ctcattaaac gtgttcaatc aactactttt cgaaatggat accatggtag 13371 gcaaaggctg ggaagacatt tacccaatgg aaacagttgc aatcgtagca ctatttcacg acctttgcaa 13441 agttggtcag tatcgtgaaa ctgaaaaatg gcgcaagaac agcgacggtg aatgggaaag ctatttagca 13511 tatgaatacg accctgagca acttacaatg ggacatggtg caaaatctaa tttccttctt caacgtttca 13581 ttcaactcac gccagttgaa gctcaagcaa ttttctggca tatgggagcc tatgatatta gtccttatgc 13651 aaatttgaat ggatgtggag cagccttcga aactaatcca cttgcattct taatccatcg cgcagatatg 13721 gccgcaactt atgtagtcga aaatgaaaac ttcgaatact ctcaaggtcc agttgaacaa gaggctgagg 13791 ttgaagaagt agttgaagaa aaacctaaga gttcaactcg taagaaacct gcgcctaagg aagaaaaagt 13861 tgaagaggct gaagaaaaac caaaagctgg aatcactcga cgtcgcaaac ctgcgccaaa agaggaagag 13931 gtagaagagc ctaaagaaga gcctaagaaa gcatcttcta aaattcgaat gcctaaaaag actgaaaagg 14001 tcgaagaggt agaaagcgca gacgagccga aagttgaaga agcagaggac gacaatgtgg tggtacctgc 14071 tggatatgtt cgagatgtct actacttcta cagtgaagtc gctgacgttt actacaagaa agatgtcgac 14141 gagcctgacg atgacagcga cattcttgta gacgaagaag agtacatgga cgcaatgtgt cctgtattag 14211 aagaagactt cttctacgaa cttgacggca aggttcacaa attagcaaaa ggtgaacgct tgccggaaga 14281 atacgacgaa gaaacttggg aacctatcac tgaagcagaa tacatcaagc gaacagaaaa acctaaagca 14351 gttgcaaaac ctactcgaaa aactccagcg ccttctcgtc gccctcgccc ttaaaagaaa ggttgaaata 14421 aaatgtgtga aaattgtcaa aacgaaacat tcaatactag aattttcaat gaagatgaaa gtggctatgt 14491 cgacgcctca ttcacttaca aggagattcg cgacaccgca gcagctatta gcaatcgagc ggtagaaaag 14561 aaagaccgtg acagcctttt agtcgctaca gttatggctc ttcccgtttc tcacgcagaa gatttaggca 14631 agagactttg tattgcaaat tctcgattgg aagcatttcg tgaagctgtt caagaggctc tcgagaatga 14701 aaaggctgaa gatttaaagg acgttatctt aggtcttatc gacgttgaca aaaaaattgg caaccttgca 14771 ttgcaattag ttgaatcagg agcattataa tggaacgaat aaagacgcta tttcacgtga tttatgtaa 14841 cggcactcat ttagaagtag cagctttgtt cgataccgtt gatgattatg atgacgttat aqaggacatc 14911 caggggtata ttgatacccc tgacctttat aatcaaagga gcattagaat ggcgccttac aatcctgaca 14981 tcaatggtga cgctattgct actgacattt tactacgact agatgatatt atctacgtcg acgcaacttg 15051 tgaaactatt aaatacgagg agcctattgc atgaacaatc agcgaaagca aatgaacaaa cgaatcgtcg 15121 aacttcgcga agactatcaa cgtgcaagag gtcgaataaa cttccttctt gctgtaaagg accacggcga 15191 agaactcgaa aaccttgaag cctttgtggg atacattgac aatctagtcg aatgttttcc tgaaagccaa 15261 cgaaatgtct tgaggctatg tgtattagat gaccttccag tcactaatgc ggccgctgaa attggatacc 15331 actatacatg ggttcaccaa cttcgagaca aagcagttga aacacttgaa gaaattttag atggggataa WO 00/32825 PCT/IB99/02040 351 15401 cattattcgc tctaaacacg gaatcgaaat taaggagaaa cttgatgaat tatatggtaa aagtcattct 15471 agttagtgtc tttgtactgt cagccttttg catgacttgc tcaatggttt atttggttac aggtaagcaa 15541 gaggaccacc gtagtaccgt cgcccttgta tttggcgctc tcgtaagctc tgcggcgttc tattcgacac 15611 tctttatcct cgcctatctg ccatgacatc acgcgcatac aaaccaattc ccacgcgcag agctagtgct 15681 aaacaagaga aggcagttgc taagcagttg ggaggaaaag tacagcctaa ttcaggagcc actgactact 15751 acaaaggtga cgtcgtaaca gactcaatgc ttatagaatg caagacagtt atgaagccac aaagttcagt 15821 cagcttgaaa aaggaatggt tcctaaaaaa tgaacaggaa aggttcgctc aaaaactcga ctattctgct 15891 atcgctttcg actttggtga cggaggcgaa cagtatatag caatgtctat aagtcagttc aagcgaatat 15961 tagaggatag aaatgataac cttatttaaa ataaacagtg aaggaacagt tactccaatt aaagggtcag 16031 ccatgcaact gtacgcagac cttattccta tacaagagga cgatatacag ttcgttgata taactggact 16101 tgaccctatt gttcgagaaa acgtacttga gctcatttca cggagccgtg taggagtttc aaaatatggt 16171 acaaacctcg accagaatga tgtcgacgat ttcctacagc acgccaaaga.agaagcgctc gactttgcta 16241 actacctaac caagctacaa agtcaacaaa agcaaaataa atagacctat ttctaggtct atttttatta 16311 ttgataaatt ccagcaattt gacgagcgca atcttctagc gcagatacta ggtggcggct ttcttgttta 16381 ccttgttcat ttcttgcttt aattctttcg ttaaggcgtt cgattcttgt agttaatttc ttgatgattt 16451 caattctagc atcaacttcc atgtcgcgag taagtgtgac tccagtttca gcgacaggac atgctttgaa 16521 tactgcaatg tcaagttcgc tctttctaat aactgagcct aggtctaagt acaagttagg attgattcca 16591 gtgaccttat attgtttctc agtttctttt acaggaatgc tttcatagtg gaaagtgtag ttcttgtgac 16661 cgtctttcca atctgctgta agataaccga aataaagtgt tgtttccata attgacctct ttctgcgtcc 16731 ttgacgcttg ttttatttat attatgatta tacgataata aaggaataaa gtcaagcact ttttacaaaa 16801 aagttgaact tttttaaata tttttttttg aaaataaaaa gccctaataa tagagctttt agtttagcag 16871 aaaattaagt tcatcttcat aagcaagaat ctgtccgtac tggtaagaaa tagctgattc aatatccggc 16941 atttcgtgga ctcctttttt aagttcgtcg atagtacagt tacaatgacc tattcttgac tgaagttcct 17011 caatcctttc gagtcgcttt tcattttgtg tatcaattgt tttcgagtct aggtgagtga aggaacttgc 17081 aatagtttga atggcttcaa aaaagtccgt tattgaaact Cctttataag aaagctcatt ccgtgtatag 17151 caggaaagca aagcgttCCa gctagtgatt tgaatttgag ggttaggaga gtttcgataa gctacaaaat 17221 ttagaatatc tttgtagtca atatcagctt cagtatgatt gttgataaat accttcattt tataaccctt 17291 ccaaatcttc gtcctcgtca tcgttttcat agcaggcgat aacttcaacc cactcgtcgt cctcaccttc 17361 gtttcgaact cgaatgctaa ggacttccat gtcctcaaca tcttcgaatc Cttcattagg tgcatatcct 17431 tcccactcta aatcgtcgta gtcgaagata gttacaagac gtccgtcaaa ttttactgtt tcctttactg 17501 ttgccatttt agtttcctcc ttatgcgata tatagtttga taatttgaga ttcgatgtca ccatagttga 17571 tgaacttaac ttggtcgacc gtttcttcca tgtaitcgcc catgtcttcg attcttccgt cttgaatcat 17641 atggccgttt tcgttgataa tttcgtacca CCattcatca ccgaattgtt tgattgcttc tttaactgtt 17711 ttcattttac tacctccact ttttcgtcca ttagtgattc gttatcatag aaccgaatac gtccatcact 17781 aagacgttct aggcttaccC atttacgacc ttgacggtca gttactttaa attcagtacc ttttgcattt 17851 acaactttca ttcctacttg caaatcttta acttttacca ttttatatga ctcctttatt tgtttttctt 17921 tatagtatta ttatacgata atgagtgaat aaagtcaagt gtttttgtaa acttttttaa attttttaat 17991 tttttttttc aaaaaaataa cgagccgaag ctacgttatt tatttatctg ctcaagggct tgttgaattg 18061 cctcatagcc tttacgacgt gctacctttc cagctttaga gccgggtgaa aagtcccaaa cagtttcgtc 18131 tactttaaag tcatccgcct tggcatagtc gagcaggagc tggatagctt tttgccattt ccgccaattc 18201 ttggaaaact cacctatatt agcacaacgc aaaacaagtg ctctagtatg ctggctagac ataatgaact 18271 ctaaaaagtt gtccaaggtt ataggaaggt cctttggaaa ctcataaggc tctttgacat cgtatttgaa 18341 aaggctgaca atttcactgt ccttaaatag ttcaccgtct ttatacataa taccttgaac aatttcagta 18411 ggctctgctc cgctatctag tacatcgcca accgtgtgac aataggcttt aagaactgca aaaaaacctg 184 81 gggcgtctgc acgcgcaacc tggagctcct taacagtcat ccaaggctga ggtttcttac aaacaatcct 18551 aattccttca aaatagctct tgtccgggtc aatagtgcct aacattgtca gcctgtttt atttatataa 18621 aggtcgaaat atacttgaat ttcatctgta ttaggcagcc acttaacagt gacttttcta taagcgatg 18691 cttttacatt tacttttttc gagagatttg tagggataag cattttcctt ttgacattta ctttttttcg 18761 ctttttgttc tttgcccatg tagtatctcc atttctgttg gtcttgcttt ttagctctgt tcagttcagc 18831 tgcttctcgc gatgcaatag tttcgagaat atgcctgttc ataggctcac aatattccgc caaagatttg 18901 ccagttatgg tggcgtcaat taagtaacca tctattgact ccttaccata aaatacaaaa tcgtcttggc 18971 atactagcct tttataatag ccatttCCtg cgcgtgtttc aattttaact aagctcattt tcacccaaac 19041 ttgtagacga taaggagttc CtggaacttC gaacaggagc ctcctttttt catcgtctac ttgtttaata 19111 catgagtttt gaaaatggat aactttccat ttattttcca tagtttcacc ttattccatg tacccgtcaa 19181 caatccataa ttgaaaaggc ttatcttctc tataaggccg tgataatttt agtccagttc ccactacatt 19251 tgaaagcgcg attaggtcat ctaggctgtC tagctcgagt tcgattacaa ggttgccagt atcaatttca 19321 caaaagtaag cgacatttcc aactttctct agtgcttcac gatacctatc atatgtcgcc tcttcgtcaa 19391 atagtcgcgc agaataaact tcgaatttca ttttagttac cgccttccaa aatttcatcg ggcataatct 19461 ttgcattctc gccatgaaac cgcccttcaa tatacgcttc aagattgaag tcatgttgag gtctgtcaat 19531 tccttccttc tttaaatttc gaaatgtgtc ctgaagcgca ttttttgttt gctcgctagg taggaccata 19601 agtgaatatt cttccacctg ctttttaaat cgaatggcta aggctgacaa aaagcctttg aggtatgaat 19671 tcttgtagga aggttcgcga gtaggaagtc ggtcaatacg gtaacgaaga taaagcaaag cagcctcata 19741 tattttagac actaattcag cgtcttgttt ttcgccgaag aaaattattc gacttttatt caagcgcata 19811 tcacgctgat taatacaaaa gcacctaaaa ttagtcgcga gaatatgacc aagttcacgt tcccaccaaa 19881 atattcgacc tgcttctttc ccaacagctt gagaagtctc gaactgttta ggttcatcaa attgttcaac 19951 ttgagcaagt gcgatattat tctttagcat caacttttga gccataagaa gggcagtttg cccctcttcg 20021 tcactcgggt tgtcatttgc taattgaata agatttttaa ttttttcaat aattttttcg ttattcatat 20091 tagtcacttt ctatcatatt ttcgagcttt cgaaaagtca atgtcgtcta cttcaattgt cttgtcataa 20161 gtccaagcgc gacaagtgtc gaaatgaaat aggctacaaa acatcttttc attatggtcg aactttcagz 20231 tacatttttc aatatctact tcaagttcga gaacgacaat agtatcaaca tttcgaagcg ataaaaaggc 20301 tagagccttt tcataacttt ctgctaggta aataactcca gctgaaggct tcaatccttc agctagaatt 20371 ttaccaagat tatcaaaatc agtggcgtga taaagtttca ttagttactt ccttacatat ctagagtcac 20441 tacataaata gaagcagttt tatcttccaa gtcctactca atagcttcct Cttcgctgag tttttcgagt 20511 tttaaaactg tcgcttcagc tacaacatta gcaaagttcg aaccgttgag aatgttttcg atatttcctg 20581 cgcctaagac ttcagcttgg tcattgttca ctaccattag gtattcatta gtaagtgctt tagcaaagtt 20651 tgaaaatttc attttatttt Ccctttattt gtttttcttt atactattat tatacaataa tgattgaata WO 00/32825 PCT/IB99/02040 352 20721 aagtaaagca ttttttataa aaaagttgaa ctttttttac aattttttga actatttaaa aattataaaa 20791 tgggtggaaa atttaggcga caatttatac ccattttcaa cctcattiat aaacaatcta atatagaaaa 20861 ggacttaata agtaaataaa aaagcgccct gaaaatacct acaaatccca tagtccgtaa gtaaaaacaa 20931 aaattagggg cgacataaaa gtcgagcact atcttaatct attaccagtc tcatatacaa tcgacacaga 21001 tttagcaggc ttttagcaaa ctttcgaaca gcatgaaaaa gcatacaatt agaggaacag attatagaaa 21071 aagcacttcc acaaacaagt tctcaaaatg ctctcaaaaa ccgtaaaatt agtaagtttg aacttttcga 21141 acttctaaac ttttcgaata atcgagccta atttagaggt cgaaaaactc aatttctcga aaagtcgaac 21211 ctgctcgaaa acctcaaaac actcgaaaag tcgagcatag aaaggggtcg aaaagtcgag aatgctcgaa 21281 aaactcaacc ggttcgaaaa cctcaatcct tcgaaaagtc gaaccattcg aaaagttcaa aagttcgaaa 21351 aactcaacca ttcgagagta ggaattaagg acataccagt tcaacctttt tagcttcaaa atcactcttt 21421 ttctcattat aggactataa attcagtcaa ttgtaagtca cgcgcaaatt tgttacaatg taaacgataa 21491 aatataaagg agggtcaata aatggcgaaa gctactggac caaaagttcg aagaggaaaa actcctccac 21561 ggccaaaaga caaaaaagga atcaaagcaa atgcgcgtgt caataaagac cagttcgtag agtatgacta 21631 taaaggcatc aagatgacaa ttaaggaacg tgatgctaga atgaaattgg aatttattag aggcatgact 21701 attcaggaaa ttgcagcccg ctatggatta aatgaaaagc gtgttggcga aatacgggct cgcgataaat 21771 gggtgaaggc taagaaagag ttcgagaatg aaaaggctct tgttactaat gatacattga ctcaaatgta 21841 tgcagggttt aaagtctcag tcaatattaa atatcacgcc gcctgggaga aactaatgaa catcgtcgaa 21911 atgtgtttag ataatcctga cagatattta tttactaaag aaggaaatat tagatggggc gcattagatg 21981 tcctttcgaa ccttatagat agagctcaaa aaggacaaga aagagcgaat ggaatgcttc cggaagaggt 22051 tcgatataga ctacaaattg agcgcgagaa aattacattg ctccgggcca aaatgggcga ccaggaaatt 22121 gaaggcgagg ttaaagataa cttcgtagaa gcactagata aagcagctca agccgtttgg caagaattta 22191 gtgacgcaac aggttcctac attaaaggag tgactgataa tgacaataag cctgagaaat aaactaccta 22261 agttcaactt cgtccctttt agtaagaaac aactccagct cctaacatgg tggacaaagg gctcaccttt 22331 tcgaactttc gatatcgtca tagcagacgg ttccattcgt tcaggaaaaa cagtatcgat ggctctttca 22401 ttttcccttt gggccatgac ggaattcaac ggacaaaact ttgccatctg tggtaagaca attcactcag 22471 ctcgacgaaa tgttattcag cctctaaagc aaatgctcac aagtcgcggg tatgaaattc gagatgttcg 22541 aaatgaaaat ctacttatta ttagacactt tagaaatggc gaagaaattg tcaactactt ctatatattt 22611 ggaggaaaag atgagtcgag tcaagacctt atacaggggg taacattagc aggtatcttc tgtgatgagg 22681 tggcactgat gcctgaatcg tttgtcaacc aagcgacagg gcgctgttcc gtaacaggtt cgaaaatgtg 22751 gttctcttgt aacccggcca atcctaatca ctacttcaag aagaactgga ttgacaaaca ggtcgaaaag 22821 cgtatcttat atcttcactt tacaatggac gacaacccta gcttgacgga tagcattaaa aggcgctatg 22891 agaaaatgta tgctggagtc ttcaggaaaa gatttattct cggcctttgg gtaacagcag atggtctagt 22961 ttattcaatg ttcaatgaag agcagcatgt caaaaagctc aatatagaat tcgaccgttt attcgtagca 23031 ggcgactttg gtatctataa tgcaacaacc ttcggccttt atggattctc gaaacgtcat aagcgctacc 23101 atctaattga gtcatactac cactcagggc gcgaggcgga agagcaacta actgaggcgg atgttaattc 23171 gaatattcaa tttagttcag ttctacaaaa gactactaaa gagtacgcaa atgatttagt cgatatgata 23241 cgaggaaagc aaatcgaata tataattctc gacccgtctg cttctgctat gattgttgaa cttcaaaagc 23311 atccttatat agctagaaag aatatcccta tcattcctgc tcgaaatgac gtgacgcttg gcatttcatt 23381 tcacgctgaa ctcttggctg agaatagatt tacactcgac cctagcaaca cgcacgacat tgatgaatac 23451 tatgcttaca gctgggacag taaagcgagc caaacgggag aagatagagt cattaaagag catgaccact 23521 gcatggatag gaacagatat gcctgtctca ctgacgctct aatcaacgat gacttcggtt tcgaaataca 23591 aatattatcc ggaaaaggcg ctagaaacta actaaacact tttatagaaa ttagtgtata atataagtag 23661 gaggatttta aacatggcta aaaaatcaaa agctatctca cacacagacg aactgattag tcagtcgttt 2g731 gacagcccct tggcaaagaa tcaaaagttc aagaaagagc ttcaggaagt tgaaaagtat tatcaatact 23801 tcgacggatt tgatgtcacg gacttgaata ctgactatgg gcaaacatgg aagattgacg aagactcagt 23871 cgactataaa cctactcgag aaattcgaaa ctatattcga caacttatca aaaagcaatc acgctttatg 23941 atgggtaaag agccagagct tatctttagt ccagttcaag acaatcaaga tgaacaggct gagaacaagc 24011 gtattctatt cgactctatt ttaaggaatt gtaaattctg gagcaaaagt acaaatgcat tagtcgacgc 24081 cacagtaggt aagcgggtat tgatgacagt agtagcaaat gccgctcaac aaattgacg ccagttttat 24151 tcaatgcctc agttcaccta tacagttgac cctagaaacc cttccagctt gctitctgtt gacattgttt 24221 atcaggacga gcgtacaaaa ggaatgagca ctgaaaaaca actttggcat cattatagat atgaaatgaa 24291 agctggaaca agtcaatcag gaattgcaac agctttagaa gacattgaag aacaatgttg gctcacttat 24361 gccttaacgg atggagagtc gaaccaaatc tatatgacag aaagtggcca aactactatc aaggagacag 24431 aggctaaact tgtagaaatt gaagacaacc taggaaacaa gattgaagtt cctttaaaag ttcaagaatc 24a01 cgccccaacc ggcttgaagc aaattccttg tcgagttatt cttaatgaac cattgactaa tgacatatac 24571 gggacaagcg atgtcaaaga ccttatcaca gtagcagata acttgaacaa aactattagt gacttacgag 24641 attcacttcg atttaaaatg ttcgagcagc ctgttatcat tgatggctct tctaagtcaa ttcaaggaat 24711 gaagattgcg ccaaacgctt tggtcgacct taagagtgac cctacttcct caatcggcgg tactggaggc 24781 aagcaagctc aagtcacttc catttcagga aacttcaact tccttccagc ggctgaaat tatttagagg 24851 gcgctaagaa agccatgtat gaactaatgg accagccaat gcctgaaaag gtacaggagg cgccatcagg 24921 aattgcaatg cagttcttat tctacgacct aatttctcga tgtgacggaa aatggattga gtgggatgat 24991 gctattcaat ggctcattca aatgctggaa gaaattttag caacagtgaa tgttgacttg ggaaatattc 25061 ctcaagatat tcaatcaagt tatcaaacac ttacgacaat gactatcgaa caccactatc caattcctag 25131 cgatgaactt tctgctaagc aacttgcgct cactgaagtt caaactaatg tacgcagcca ccaatcttac 25201 attgaagaat tcagtaagaa ggaaaaggcg gacaaggaat gggaacgcat tttggaagaa cttgctcagc 25271 ttgacgaaat ctcagctgga gcattgcctg tattagcaaa cgaattaaac gaacaagagg agcctcaaga 25341 tgaaacgagt gaagaagacg aagttgatga caaagaaaaa gaacaaactg aacaaccaac cgaagaagga 25411 gtcgacccag acgttcaagg ttaattgtga ccattgtgag cataagttcg accttacatc taaacagatt 25481 atttcgaaac atatcgaaaa gggcgtagag tggagattct tcgaatgtcc taagtgccat tatcggtcac 25551 ccacttatgt aggaaacaag gaaattgaaa accttattcg atttagaaat acttgtcgag ctaaaatgaa 25621 gcaggaactt caaaaaggag ctgctgctaa tcaaaacact taccattcat atcgaattca ggatgagcaa 25691 gctgggcata aaatctcagg gcttatggcg aagctaaaga aggagataaa cattgaaaaa cgagaaaaag 25761 aatgggtatc tatatagctg ggaaaaggct attcatgaaa ataatattcg tctaaccctt gaacaggaac 25831 aagctgtact gaaagccttc agcgatgcag gaactgattt aattgcaaag attaaaaagt ctcgaaatgg 25901 atacttgcct aaaagaatct aaaaagacta cgcttacgac ctgcacgctg ttcttgttca actaatgact 25971 gaatactctc ataaggcggc aatgaacgca gtagatggcc aggtagttca tattctacaa gtattagcag WO 00/32825 PCT/IB99/02040 353 26041 aagatggaaa tgctacggct gaaaagttcg aaaaggaagt cagggctgca tctttagtat tttcacgaag 26111 agcagccgag gcagttgtCa aaggtgaaat ctataaggac ggcaaaaacc tctcgaaacg tgtttggtct 26181 tcagccgcac gcgcaggaaa tgatgttcaa caaatagtca cacaaggcct agcaagtgga atgtctgcta 26251 cagatatggc taaaatgctc gagaaatata tcgaccctaa ggttcgaaaa gattgggact ttgataagat 26321 agctgagaag ctagggaaac ctgctgctca taaatatcaa aatctcgaat acaatgccct tcgacttgct 26391 cgaactacca ttagCcattc cgccacagct ggagtgagac aatggggcaa ggttaatcct tatgctcgaa 26461 aagttcaatg gcattctgtt cacgctccag gtcgaacgtg tcaagCgtgt atcgatttag atggtgaagt 26531 atttcctatc gaagaatgtc ctttcgacca tcctaatgga atgtgctacc aaactgtatg gtacgaaaac 26601 tcactcgaag aaatcgctga tgagttgaga ggctgggtag acggagaacc taatgatgta ttagacgaat 26671 ggtacgacga tttaagttca ggaaaagttg agaaatacag cgacctcgac tttgttaaaa gttattaggc 26741 tcggttcaat accgagtctt tttgtctata aattgtctaa tttcgagaac cttcgaaaag tagtaaaatg 26811 atattcagtt atgttataat ataagttgaa aaggaacctt gtcgccttaa tgactcgaaa ttggtttcac 26881 tgttccaatt aaataaaaac agcagattca gccggagggc ggaaaactca ggaggaaaat aaatggctta 26951 tcaattagaa gacttgttaa aaggtctaga tgaaccaact atcaaacagg tgaaggaaat tatttcgaaa 27021 acttcgaaag aactcgatgc taaaattttc attgacggcg acggtcaaca ttttgtacct cacgcacgtt 27091 tcgatgaagt tgttcaacag cgcgatgcag ctaacggctc aattaattct tataaagaac aagtcgcgac 27161 gctttctaaa caggtcaaag ataacggtga tgcgcagacc actatccaaa accttcaaga gcaactcgac 27231 aagcagtctc aacttgcaaa aggcgctgtg attacttcag ctcttcatcc gttgattagt gactccattg 27301 ctccagcagc agacattctt ggatttatga accitgacaa cattacggtc gaaagtgacg gtaaagttaa 27371 aggtcttgat gaagagttga aagctgttcg tgagtctcgt aaatacttat tcaaagaagt cgaagttccc 27441 gcagaacaag aggctcaagc taagtcgcca gccgggactg gaaatttagg aaatccaggt cgtgtcggtg 27511 gtggtgttcc cgaacctcgt gaaatcggct cttttggtaa gcaacttgct gctgctcaac aaacggcagg 27581 agcacaagaa caatcatcat tctttaaata ataggaggaa ctaactatgc ctaatgtgcg agttaagaaa 27651 actgatttta atcaaaccac tcgaagcatt gtcgcaattc ctgaccacta cgttgctttg gctgctcaaa 27721 ttccagctac cgcagcaact caagtaggga acaagaaata cattcttgcc ggaacttgcg tgaaaaatgc 27791 tactacattt gaaggacgca aaactggact cgaagtagta tctaccggtg aacaattcga cggagttatc 27861 ttcgctgacc aagaagtgtt tgaaggtgaa gaaaaagtaa ccgtgacagt attagttcac ggattcgtca 27931 aatatgcagc ccttcgaaaa gttggcgatg ctgtgcctga atctaaaaac gcaatgattc ttgtcgttaa 28001 ataggaggaa ttatagatga atatttatga ttatatcaac gcaggggaga ttgctagcta cattcaagca 28071 cttccttcaa acgctcttca ataccttgga ccaactcttt tccctaatgc tcaacaaaca gggacagaca 28141 tttcatggct caagggtgca aataatttgc cagtaactat ccagccatct aactacgacg cgaaagcaag 28211 tcttcgtgaa cgtgctggat ttagcaaaca agctactgag atggcattct tccgtgagtc tatgcgactt 28281 ggtgaaaaag accgtcaaaa cttgcaaatg ctattgaacc aaagttcagc tcttgcccaa Ccacttatca 28351 ctcaactcta taatgatact aagaaccttg tagacggtgt tgaagcgcaa gcagaataca tgcgtatgca 28421 attgcttcaa tacggtaaat tcactgtcaa atcaactaac agcgaggctc aatacactta cgactacaac 28491 atggatgcta agcaacaata tgcagtcact aagaaatgga ctaacccagc tgaaagtgac cctatcgctg 28561 acattttagc agcaatggat gacatcgaaa atcgtacagg tgttcgccct actcgaatgg tcttgaaccg 28631 aaacacttat aaccaaatga ctaagagtga ctctatcaag aaagctcttg caattggtgt tcaaggttct 28701 tgggaaaact tcttgcttct tgcaagtgac gctgagaaat tcatcgctga aaaaacaggt cttcaaatcg 28771 ctgtctactc taagaaaatt gctcagttcg ctgacgctga caaacttcct gacgttggta acattcgtca 28841 gttcaacttg attgacgacg gtaaagtggt attgcttcca cctgacgcag ttggtcacac ttggtacggt 28911 actactccag aagcattcga cttggcttca ggcggaacag acgctcaagt tcaagttctt tcaggcggac 28981 ctaccgttac aactatctt gaaaaacatc ctgtcaacat tgcaacagtt gtatcagctg ttatgattcc 29051 atcattcgaa ggaattgact atgtaggagt tctcacaact aattaggagg tcgctatatg gctacattga 29121 aagctcttag caccttaatc gtttccggag cagtagtgca ttcagggtcg gtattttctt gccctgaagc 29191 gcttgcttcg tctttaattg aacgcaattt tgcgttcgag attaaggcgg ctgaagatgg agaaacggta 29261 gaaactgttc ctcaaacaat tgaatcagtt gaagaaattg acgaagttga acaaatgcgc gaagagtatg 29331 cggctaaaac cgttcctgag ctcgttgaat tagcaagagc taatggaatt gacatttctt caatttctcg 29401 aaaaagcgaa tatatcgacg ctttaattaa gtacgaacta ggagagtaaa atggcagctc aaacggacat 29471 tgaattagtc aaaatcaata tcgataacga taattctccg tcaccaatga ctgaccaaag tatctcagct 29541 cttttagaca agcataaatc tgtcgcctat gttagttata tgatttgctt aatgaagacc cggaatgacg 29611 tggtaaccct tggacctatc agtctaaaag gtgacgcaga ctactggaaa caaatggcgc aattctatta 29681 tgaccaatat aagcaagaac agcttgaaac tgatgaaaag tcgaacgctg gttcgacaat cttaatgaaa 29751 agggctgatg ggacatgagt tatgacgtga attatgtaa gaatcaagtt cgtagagcca ttgaaaccgc 29821 tcctactaaa atcaaggtac ttcgaaactc ttgggtcagt gatggatatg gaggaaagaa aaaggataaa 29891 gcgaatgaag tcgtagcaga cgaccttgtt tgtttagttg ataattcaac tgttcctgac cttttagcca 29961 attctactga cgcgggaaaa atttttgccc aaaatggagt gaaaattttc attctatatg atgaaggcaa 30031 aatcattcaa cgagccgata ctatcgaaat taaaaactca ggaagacggt acagggtagt agaaacccac 30101 aatcttctcg agcaagacat tttgatagaa cttaaattgg aggtgaacga ctaatgtctc agcctgaatt 30171 agtatggaag cctgaagaat ttgttagtaa ctgtgaacgg tatcgaaaca agtttcaagt cgctgtcata 30241 acagtctgcg aagtcgctgc tactaagatg gaagaatacg caaagacgca tgctatttgg acagaccgta 30311 cagggaatgc tcgacagaaa ctcaaaggag aagctgcttg ggtaagcgca gaccaaatca tgatagctgt 30381 atcacatcac atggactacg ggttttggct agaactagct catggtcgaa aatacaaaat tctcgaacag 30451 gctgtagaag acaatgtcga agaacttttt agagcgttga gaaggttatt agactaggag tgaacatgac 30521 taaacgaacg acaatgatgg acagattgaa ggaaattctt cctacatttc agctctcgcc tgctcctatg 30591 cttccaggag ttgaatttga cgagcaagat acagataggc cggatgacta cattgttctt cgatatagtc 30661 atagaatgcc cagcgcaaca aatagcctag gaagttttgc ttattggaaa gttcaaatct acgtccattc 30731 aaactcaatt attggtatcg acgaatatag cagaaaggtt cgaaacatta tcaaggacat gggctacgaa 30801 gtaacctatg cagaaactgg tgactacttc gacacaatgc tttctagata ccgactagaa atcgaatata 30871 gaattccaca aggaggaaac taataatgag taaagacatt ctttacggaa tcaagctcgt gcaaarcgag 30941 gagcttgacc cattgactca gttgccaaaa gtcggcggag ctaactttgt cgtagatacg gcagaaacag 31011 cagaactcga agccgtgacc tcggagggaa ctgaagatgt gaaacgcaat gacacgcgca ttcttgctat 31081 cgtgcgtact ccagaccttt tatacggtta tgacttaaca ttcaaggaca acacgtttga ccctgaaatc 31151 atggccctaa ttgaaggtgg tacagtacgt caacaaggcg gaactattgc tggatacgac accccaatgc 31221 ttgcacaagg tgcttctaat atgaaaccat ttagaatgaa catctatgtg ccaaactatg taggtgactc 31291 aattgtcaac tacgtgaaaa tcactttgaa taacgtacc ggtaaagctc cagggctttc aatcgggaaa WO 00/32825 PCT/IB99/02040 354 31361 gagttctacg ctcctgagtt caacatcaag gcacgtgaag caaccaaagc aggtttgcca gttaagtcaa 31431 tggactatgt ggcacaactt ccagcggttc ttcgtcgcgt gacattcgat ttgaacggtg gaacaggaac 31501 cgccgacgca gttcgagttg aagcaggtaa gaagatttct ccaaaaccag ttgaccctac cttaacaggt 31571 aaggctttca aaggctggaa agttgaagga gaatcaacta tttgggactt cgacaaccac atgatgcctg 31641 accgagacgt caaactcgta gcacaatttg catagaaatt tagaaagaag ggtctgttat gactaatatt 31711 atcacagctg agcagtttaa gcaacttgca tttcaaatca tcgcacttcc aggattttca aaaggtagtg 31781 aacctatcca tgttaaaatt cgagcagcag gtgtcatgaa cctaatcgct aacgggaaaa tccctaatac 31851 gcttttaggt aaagtgacag aactgtttgg agaaacttcg acagtcacta aagacaatgc tagtctagca 31921 tcaattactg accaacagaa gaaagaagcg ctcgaccgat tgaacaaaac cgataccggt attcaagaca 31991 tggctgaact tcttcgagta ttcgcagaag cttcaatggt agagcctact tacgctgaag tcggcgagta 32061 tatgacagat gagcaactta tgacaatctt cagtgcaatg tacggtgaag tgactcaagc tgaaaccttt 32131 cgtacagacg aaggaaatgt ctaatgtcat agcagtcgct actgaatttc atattagacc tagcgaggtg 32201 gtcgggatgc aaactgattt aggcaaatac tgcttcgacg cagcagccgt tgcttatatt agatatttgc 32271 aggaagacaa gactcctagg tatcctggtg acgaaaagaa aaatccagga ttgcaaatgc ttatggagtg 32341 actattttca gtcgctcctc tttttgtata tagaaaggaa attacatgga ttttgggtca attgcagcaa 32411 aaatgacttt ggatatctca aacttcacaa gtcaattaaa tcttgctcaa agtcaagcgc aacggctcgc 32481 actagagtct tcgaagtcct ttcaaattgg ttctgcttta acaggattag ggaaaggact tacgactgcg 32551 gttacccttc ctcttatggg atttgcagcc gcctctatta aagtagggaa tgaattccaa gctcaaatgt 32621 cccgtgttca agctattgca ggagcgacag cggaagagct tggtagaatg aagactcaag caatcgacct 32691 tggtgctaaa actgctttta gtgcaaaaga ggcggctcaa ggtatggaaa atctagcttc agccggtttc 32761 caggtaaatg aaatcatgga cgctatgcca ggggtacttg acctggctgc cgtatctgga ggagatgtgg 32831 ccgcgagctc cgaggccatg gctagttcac ttcgagcctt tggattagag gcaaaccagg cgggtcacgt 32901 ggctgacgta tttgctcgag cagcagctga tacgaacgca gaaactagcg acatggcaga ggcgatgaaa 32971 tacgtcgcac ccgttgctca ctctatgggc ttgagccttg aagaaacggc tgcgtctatt gggattatgg 33041 ccgacgccgg tattaagggc tcgcaagccg gaaccacgct tagaggcgct ctctcgcgta ttgccaaacc 33111 tacgaaagcg atggtcaaat caatgcagga attaggagtt tcgttctacg acgcgaacgg aaacatgatt 33181 ccactaagag aacaaatcgc tcaactgaaa acagctacag caggactaac acaagaggaa cgaaatcgtc 33251 accttgttac cttgtatggc caaaactcgt tgtcaggtat gcttgcacta ttagacgcag gtcctgagaa 33321 attggataag atgaccaatg ctctcgtgaa ctcggacgga gctgctaagg aaatggcaga aactatgcag 33391 gacaaccttg ctagtaaaat cgagcaaatg ggaggagctt tcgagtctgt tgctattatt gttcaacaaa 33461 tccttgagcc tgcacttgct aaaatcgtgg gagcaatcac aaaagttctc gaagcattcg taaatatgtc 33531 acctatcggt caaaagatgg ttgtcatatt cgcaggaatg gttgcagccc ttggaccact gcttctaatt 33601 gcaggaatgg tgatgacaac tattgtcaag ttaagaattg ctattcagtt tttaggtcca gcatttatgg 33671 gaacgatggg aaccattgca ggagttatag caatattcta tgctctggtc gccgtgttca tgatagccta 33741 cacaaaatcg gagagattta gaaactttat caacagtctt gcgcctgcta ttaaagctgg gtttggagga 33811 gcgttggaat ggctacttcc acgactgaaa gagttaggag aatggttaca gaaggcaggc gagaaggcga 33881 aagagttcgg tcagtctgta gggttaaag tgtcaaaact gctcgaacag tttggaataa gtatcggtca 33951 ggcaggaggc tcgattggtc agttcattgg aaatgttctc gaaaggctag gaggcgcatt tggaaaagta 34021 ggaggagtca tttcaattgc tgtttcactt gtaacaaaat tcggtctcgc atttctaggg attacaggac 34091 cactcgggat tgctattagt ctgttagttt catttttgac agcttgggct agaacaggtg agttcaacgc 34161 agacggaatt actcaagtat tcgaaaactt gacaaacaca attcagtcga cggctgattt catctctcaa 34231 taccttccag tctttgtcga aaaaggaaCt caaattttag ttaagattat tgaaggaatt gcatctgctg 34301 ttcctcaagt agttgaagtg atttcacaag tcattgaaaa tattgtgatg acaatttcga cagttatgcc 34371 tcaattagtc gaagcaggaa ttaagatact cgaagcgctt ataaatggtc ttgttcaatc tcttcctact 34441 atcattcaag cagctgttca aattatcact gctttattca atggtcttgt tcaggcactt cctacgctta 34511 ttcaagcagg tcttcaaatt ttgtcagctc tcataaacgg actagttcaa gcgcttccgg caattattca 34581 agcagctgtt caaattatca tgtcgcttgt tcaagcacta attgaaaact tgcctatgat aatcgaagca 34651 gcgatgcaga ttataatggg tctagtcaac gcactgattg aaaatatagg acctatctta gaagcaggga 34721 ttcaaattct aatggcttta atcgagggac ttattcaagt gcttcctgaa ctaattacag cagcgattca 34791 aatcattact tcactattag aagcaatctt gtcgaacctt cctcaacttc tagaagccgg agttaaattg 34861 cttttatcac ttcttcaagg gttgctaaat atgcttcctc aactaattgc aggggctttg caaatcatga 34931 tggcacttct taaagcagtt atcgacttcg tccctaaact tcttcaagca ggtgttcaac ttcttaaggc 35001 attgattcaa ggtattgctt cacttctcgg ctcactttta tcgacagctg gaaacatgct ttcatcatta 35071 gttagcaaga ttgctagctt tgtgggacag atggtttcag gaggtgcgaa cctgattcga aacttcatta 35141 gtggtattgg gtcaatgatt ggttCagctg tctctaaaat tggcagcatg ggaacttcaa ttgtttctaa 35211 ggttactgga ttcgctggac aaatggtaag cgcaggggtc aaccttgttc gaggatttat caatggtatc 35281 agttccatgg taagttctgc ggtaagtgcg gcggctaata tggctagcag tgcattaaat gccgttaagg 35351 gattcttagg tattcactct ccttcacgtg tcatggagca gatgggtatc tatacgggtc aagggttcgt 35421 aaatggtatt ggtaacatga ttcgaactac acgtgacaag gctaaagaaa tggctgaaac tgttactgaa 35491 gctctcagcg acgtgaagat ggatattcaa gaaaatggag ttatagaaaa ggttaaatca gtttacgaaa 35561 agatggctga ccaacttcct gaaactcttc cagctcctga tttcgaagat gttcgtaaag cagccggttc 35631 gcctcgagtg gacttgttca atacaggaag tgacaaccct aaccaacctc agtcacaatc taaaaacaat 35701 caaggcgagc aaaccgttgt caacattgga acaatcgtag ttcgaaacaa tgacgacgtt gacaaactgt 35771 cgagaggatt gtataataga agtaaagaaa ctctatcagg gtttggtaac attgtaacac cgtaaaggag 35841 aaatagatgg ctagcagaca gacgctattg gtcgacggaa ttgaccttgt cgacaaaggt gcaaccgtgc 35911 tagaatatgt aggactcact ttcgcaggat ttaaggactc aggatttaaa aaccctgaag gcatagacgg 35981 agtattagat tctccgtcta atgctatgtc cgctcttact ggaagcgtga ccttaatgtt ccacggagaa 36051 accgaaaagc aagttaatca aaaatacagg cagttcaaac aatttattcg ctcgaagtca ttttggagaa 36121 tttcgacact tgaagaccct ggatactatc gaacgggaaa atttttagga gaaaccgagc aaggaaaapt 36191 tgtagacgtt caagccttta aagatacttc ccttgtagtt aaattaggga ttcagttcaa agatgcttac 36261 gagtacagcg actcaactgt tcgaaaggtt tataagtttc aacccgcttt gggaggcgat agcttaccta 36331 acccaggaag acctactcga caatttagag tagaaataag aactacttct caaatcaaag gatattttcg 36401 aattggcgaa aaaagttcag gacagtttgt tgagttcggt actaattcag tattgatgga aagtggctcg 36471 attattattc taaatcttgg aacttttgaa cttattaaaa ttagcagtgc aaatcaagcg actaacttat 36541 ttagatacat taaacgaggc gcattcttca agattcctaa tggaaattca acaattacca ttgaataccg 36611 agccgatgac gcagcagctt ggacCtCtaC tcttcccgct caagttgaac tgtttctaaa tccgtcttac WO 00/32825 PCT/IB99/02040 36681 tattagaaag ggaatatatg attgacaata atttacctat gagtccaatt cctggcgaaa ttgttcaagt 36751 atatgaccaa aacttcaatc taattggagc aagtgatgaa atctttagca agcattacga agacgaaatt 36821 gtgactcgag ctcgaggaaa agaaactttc acttttgaaa gtattgaaac ctcatctatc tatcaacact 36891 taaaggttga aaacattatc cagtatggag gaagatggtt tcgaattaaa tatgctcagg acgtagaaga 36961 tgtcaaaggg cttaccaagt ttacctgcta cgcattatgg tatgaactag cagaaggctt gcctaggaag 37031 ttgaaacacg ttgcttcttc tgtaggcgct gtcgcgctag atattatcaa agacgcaggt gaatgggttc 37101 gactagtttg tcctcctgac ggtgctaaca aacaagttcg aagcataaca gccgcagaaa attcaatgct 37171 ttggcatctt cgatatcttg caaagcaata caatttagaa ttgacatttg gttatgaaga aattatcaag 37241 caagaggtta gaattgttca aaccgttgta tttcttcagc cttatgtcga gtctaaagta gactttcctc 37311 ttgtagttga agagaatttg aaatatgtca ctaggcagga agattctcga aacctgtgta cggcttacaa 37381 gttgacaggt aaaaaggaag aaggcagtca agagccttta acgtttgctt ctatcaacaa tggaagtgaa 37451 tatctcattg atgtttcgtg gtttactaca cgccacatga agcctcgata tattgctaaa tctaaaagcg 37521 acgaacattt tagaattaaa gaaaatttga tgagtgctgc gcgtgcttat cttgacatct acagtcgccc 37591 actaattgga tatgaggctt cagcggtcct ttataacaag gttcctgact tgcatcatac tcaactaatt 37661 gtcgacgacc attatgatgt tatcgagtgg cgaaagatat ctgctcgaaa aattgactac gacgaccttt 37731 caaactctac tatcattttc caagaccctc gaaaagactt gatggacttg ctaaatgagg acggcgaagg 37801 agtcctttca ggggaaactg taaatgagtc ccaagttgtt attagatacg cagatgacat tttagggact 37871 aattttaatg cagaatctgg gaaatacatt ggtgtcctta atactaataa gaaaccgagc gaattagttc 37941 ctgacgactt tacatggatt cgactagaag gtcctaaagg tgacgcaggt ttaccgggag ctcctgggcg 38011 tgatggagtc gacggtgtac ctggaaagag cggagtaggg atagcagata cagctatcac ttatgctgta 38081 tccgtttccg gaacgcaaga gcctgaaaat ggatggagcg aacaagttcc tgaactcata aaaggtcgat 38151 tcttgtggac taaaacattt tggagatata ctgacggctc acatgaaact ggatactccg ttgcctatat 38221 agggcaagac ggaaattccg gaaaagacgg aatcgcaggt aaggacggag taggtatagc cgcaactgaa 38291 gtcatgtatg caagttcgcc atctgctact gaagctccag ctggtggatg gtctacgcaa gttcctaccg 38361 tcccaggtgg tcagtattta tggactcgaa caagatggcg ctacactgac caaactgatg aaattggata 38431 ttcagtttca agaatgggcg agcagggtcc taaaggtgac gcaggtcgtg acggtattgc aggaaagaac 38501 ggaatcagggt tgaagtcaac ttcagtttct tatggaatta gtcccactga ttctgcgatt cctggagtat 38571 gggcttcaca agttccttct ttaatcaaag gtcaatatct ttggactcga actatttgga cctataccga 38641 ttcaactacc gaaacgggct atcaaaaaac ctacattcca aaagacggga atgacggtaa aaatggaatt 38711 gctggtaagg atggggtagg aattaagtct acgaccatta cctacgcagg ctcaacctca ggaacagttg 38781 cgcctacttc aaattggact tctgctattc caaatgttca accgggattc ttcttgtgga cgaaaactgt 38851 ttggaactat actgatgaca ctagcgaaac aggttactca gtttccaaga taggtgaaac aggtcctaga 38921 ggagttcaag gtcttcaagg tcctcaaggg cttcaaggaa ttcctggacc tgcaggagct gacggacgtt 38991 cgcaatatac tcacctcgct ttctctaata gtccaaacgg tgagggattt agtcatactg acagcggacg 39061 agcatacgtc ggtcagtatc aagatttcaa tcccgtccat tcaaaagacc ctgcagccta tacatggacg 39131 aaatggaagg ggaatgacgg agctcaaggg atacccggga agccaggcgc agacggtaag actaattatt 39201 tccatatagc ttacgcttca agtgcagacg gatcacgtga gttcagtttg gaagataata atcaacaata 39271 tatgggttat tactccgatt atgagcaagc agatagcagg gatcgaacta agtatcgatg gtttgaccgc 39341 cttgccaatg ttcaagtggg aggtcgaaac gagttcctta attctttatt tgaatttggt ttaaaacctc 39411 gctattctag ttacaatcta atggacggac aagatcaaac gcaaggacag atatctgcta ctattgacga 39481 acgtcaacgg ttcaaaggtg ctaactcttt acgacttgac tcaacatgga acggtaaacc gcagaaccaa 39551 aaactgacct tttctttagg aggagatacg cgattaggta ctccaaccga gtggtctaat ttagaaggtc 39621 gtatcagttt ctgggctaag gcctctagga acggagtgag cttagctgca cggccgggtt atcgtagtaa 39691 cgtatttacc gcaaccttaa ccgatcaatg gaagttctac gattttaaat tctttgacaa agttaattca 39761 aattgtaccg ctgaagcaat tttccatgta ttcactcaaa gttgttcagt gtggctcaat catattaaaa 39831 tcgaacttgg taatatctct actcctttta gtgaagcaga ggaagacctt aaatatcgaa ttgactcaaa 39901 agccgatcaa aagctaacta accaacagtt gacggcactc acggaaaagg Ctcaactaca tgacgcagaa 39971 ctgaaagcta aggctacaat ggagcagtta agtaacttag aaaaggctta tgaaggtaga atgaaagcta 40041 atgaagaagc tatcaaaaaa tcggaagccg acctaatctt agcggcaagt cgaattgaag ctactatcca 40111 agaacttggc gggctacggg aactgaagaa gttcgtcgac agttacatga gctcttctaa tgaaggtca 40181 attatcggta agaacgacgg tagctctacc attaaggtat caagtgaccg aatttctatg ttctccgcag 40251 ggaatgaagt tatgtacctt acgcaagggt tcattcacat cgataacggg atctttaccc aatccattca 40321 agtcggccga tttagaacgg aacaatactc gtttaatcca gacatgaacg tgattcggta tgtaggataa 40391 ggagaataac atgacaaaat ttatcaactc atacggccct cttcacttga acctttacgt cgaacaagtt 40461 agtcaggacg taacgaacaa ctcctcgcga gttagttggc gagctactgt cgaccgcgat ggagcttatc 40531 gaacgtggac ttatggaaat attagtaacc tttccgtatg gttaaatggt tcaagtgttc atagcagtca 40601 cccagactac gacacgtccg gcgaagaggt aacgctcgca agtggagaag tgactgttcc tcacaatagt 40671 gacgggacaa agacaatgtc cgtttgggct tcgtttgacc ctaataacgg cgttcacgga aatatcacta 40741 tctctactaa ttacacttta gacagtattc caaggtctac acagatttct agttttgagg gaaatcgaaa 40811 tctaggatct ttacatacgg ttatctttaa ccgaaaagtg aactctttta cgcatcaagt ttggtaccga 40881 gttttcggta gcgactggat agatttaggt aagaaccata ctactagcgt atcctttacg ccgtcactgg 40951 acttagcaag gtacttacct aaatcaagtt ccggaacaat ggacatctgt attcgaacct ataacggaac 41021 tacgcaaatt ggtagtgacg tctattcaaa cggatggagg ttcaacatcc ccgattcagt acgtcctact 41091 ttttcgggca tttctttagt agacacgact tcagcggttc gacagatttt aacagggaac aacttcctcc 41161 aaatcatgtc gaacattcaa gtcaacttca acaatgcttc cggcgcttac ggatccacta tccaagcatt 41231 tcacgctgag ctcgtaggta aaaaccaagc tatcaacgaa aacggcggca aattgggtat gatgaacttt 41301 aatggctccg ctaccgtaag agcatgggtt acagacacgc gaggaaaaca atcgaacgtc caagacgtat 41371 ctatcaatgt tatagaatac tatggaccgt ctatcaattt ctccgttcaa cgtactcgtc aaaatcctgc 41441 aattatccaa gctcttcgaa atgctaaggt cgcacctata acggtaggag gtcaacagaa aaacatcatg 41511 caaattacct tctccgtggc gccgttgaac actactaatt tcacagaaga tagaggttcg gcgtcggga 41581 cgttcactac tatttcccta atgactaact cgtccgcgaa cttagctggt aactacgggc cggacaagtc 41651 ttacatagtt aaggctaaaa tccaagacag gttcacttcg actgaattta gtgctacggt agctaccgaa 41721 tcagtagttc ttaactatga caaggacggt cgacttggag ttggtaaggt tgtagaacaa gggaaggcag 41791 ggtcaattga tgcagcaggt gatatatatg ctggaggtcg acaagttcaa cagtttcagc tcactgataa 41861 taatggagca ttgaacaggg gtcaatataa cgatgtttgg aataagcgtg aaacagagtt tacatggcga 41931 agtaacaaat acgaggacaa ccctacggga actcgaggtg aatggggact atttcaaaat ttctggttag WO 00/32825 PCT/IB99/02040 356 42001 atagctggaa aatggttcaa tccttcatta caatgtcagg aagaatgttc atcaggacag cgaacgatgg 42071 aaacagctgg agacctaaca agtggaaaga ggttctattt aagcaagact tcgaacagaa taattggcag 42141 aaacttgttc ttcaaagtgg gtggaaccat cactcaacct atggcgacgc attctattcg aaaactcttg 42211 acggcatagt atatttgaga ggaaatgtgc ataaaggact tatcgacaaa gaggctacta ttgcagtact 42281 tcctgaagga tttagaccga aagtttcaat gtatcttcag gctctcaata actcatatgg aaatgccatt 42351 ctatgtatat acactgacgg aagacttgtg gtgaaatcga atgtagataa ttcttggtta aatttagaca 42421 atgtctcatt tcgtatttaa tttgagctga aatcatgtta taatattttt tagaaaggag gtgagaacta 42491 tgttgaacct tacaaaatcg cgccaaattg tggcagagtt cactattgga caaggagctg aaaagaaact 42561 tgtcaaaaca acgattgtga acattgatgc aaacgcagta tcaaccgtct ctgaaactct tcatgaccca 42631 gacttgtatg ctgcgaaccg tcgagaactt cgagctgacg agcaaaaact tcgcgaaact cgttacgcaa 42701 tcgaagatga aattctagct gaacagtcaa agactgaaac agctctaaca gctgaataag gaggcgtcaa 42771 tctatgccaa tgtggctaaa cgacacagca gtcttgacga cgattattac agcgtgcagc ggagtgctta 42841 ctgtcctact aaataagtta ttcgaatgga aatcgaataa agccaagagc gttttagagg atatctctac 42911 aactcttagc actcttaaac agcaggtcga cgggattgac caaacgacag tagcaatcaa tcaccaaaat 42981 gacgtcattc aagacggaac tagaaaaatt caacgttacc gtctttatca cgacttaaaa agggaagtga 43051 taacaggcta tacaactctc gaccatttta gagagctctc tattttattc gaaagttata agaaccttgg 43121 cggaaatggt gaagttgaag ccttgtatga aaaatacaag aaattaccaa ttagggagga agatttagat 43191 gaaactatct aacgaacaat atgacgtagc aaagaacgtg gtaaccgtag tcgttccagc agcgattgca 43261 ctaattacag gtcttggagc gttgtatcaa tttgacacta ctgctatcac aggaaccatt gcacttcttg 43331 caacttttgc aggtactgtt ctaggagttt ctagccgaaa ctaccaaaag gaacaagaag ctcaaaacaa 43401 tgaggtggaa taatgggagt cgatattgaa aaaggcgttg cgtggatgca ggcccgaaag ggtcgagtat 43471 cttatagcat ggactttcga gacggtcctg atagctatga ctgctcaagt tctatgtact atgctctccg 43541 ctcagccgga gcttcaagtg ctggatgggc agtcaatact gagtacatgc acgcatggct tattgaaaac 43611 ggttatgaac taattagtga aaatgctccg tgggatgcta aacgaggcga catcttcatc tggggacgca 43681 aaggtgctag cgcaggcgct ggaggtcata cagggatgtt cattgacagt gataacatca ttcactgcaa 43751 ctacgcctac gacggaattt ccgtcaacga ccacgatgag cgttggtact atgcaggtca accttactac 43821 tacgtctatc gcttgactaa cgcaaatgct caaccggctg agaagaaact tggctggcag aaagatgcta 43891 ctggtttctg gtacgctcga gcaaacggaa cttatccaaa agatgagttc gagtatatcg aagaaaacaa 43961 gtcttggttc tactttgacg accaaggcta catgctcgct gagaaatggt tgaaacatac tgatggaaat 44031 tggtattggt tcgaccgtga cggatacatg gctacgtcat ggaaacggat tggcgagtca tggtactact 44101 tcaatcgcga tggttcaatg gtaaccggtt ggattaagta ttacgataat tggtattatt gtgatgctac 44171 caacggcgac atgaaatcga atgcgtttat ccgttataac gacggctggt atctactatt accggacgga 44241 cgtctggcag ataaacctca attcaccgta gagccggacg ggctcattac tgctaaagtt taaaatatag 44311 agaggaggaa gctcttttct taatattgtt tctcttaatc ccgcaaggtt tcgaccctgc ggggttttgt 44381 gtcgtatatt actctattta cttattcgaa gatttcaatt ataattaaat agtcaacatg attcatgatt 44451 gttgatatga ccctttccgc cctacataat ttgtggggcg tttatttttt ataaaaattt tttacaaaat 44521 gcttgacaac aitcactcat tatcgtataa tacaattata aaaataaata aagccgaaag gcgaggagga 44591 cattatgtca aaaattaaat tcgaaaacct taaaaaaggc gatgttgtgc tacgagctaa atctcaaacg 44661 aagtttaaaa tcgtttcaat tttagcagac gaaaagaaag cagaccttga atcattagaa gacggaggtg 44731 aacttcacct ttcagcttca actctcgaac gttggtacac aatggaagat gaaactgaac ctaaaaaaga 44801 agaagctgct aaacctgcta aaaaggctgc tcctgcagtt gctcgacctg ctcgaaaagg tagagtcgtt 44871 cccaaaccta aaaaagaagt ccttgaggaa gaaattcctg aagttaagga acagccggaa gaagttggtt 44941 cagttagtga gaaatctact gttcgaaaac ctgctcctaa aaaagaaagc gtgatggcga ttactaaggc 45011 tcttgaaagt cgaattgttg aagcctttcc tgcgtctact cgaatcgtca ctcagtctta catcgcctat 45081 cgctctaaga agaacttcgt tactatcgaa gaaactcgaa aaggtgtttc tattggagtt cgcgcaaaag 45151 ggttgacaga agaccaaaag aaacttcttg catctattgc tcctgcatct tacgaatggg cgattgacgg 45221 aatttttaaa ctcgtcaagg aagaagatat tgacaccgca atggaattga ttgaagcttc tcacctttct 45291 tcgctatgat tgaaatcgtt atagcacgtt cgaaagctag gcgaggtcga accctattta ttgaaacatg 45361 ggcaagcact gatgaagatg cagttaaaat ggcagaaaag atttccagct tgeccaatgt agtcgagacg 45431 tcttctaata acttcgaact accttataag tatttcaata atgttataga cgctctagat gaatgggagc 45501 ttcacatctt cggcgaactt gataaagatg ttcaagacta cattgactct cgaaaccgaa tagcttcttc 45571 aagcaatgag cagttttcgt tcaagactac tccattcgcg caccaggttg aatgtttcga atacgcacaa 45641 gagcatccat gtttcctttt aggcgatgag caaggtttag ggaaaactaa acaggcaatt gatattgcag 45711 ttagcaggaa ggcaagtttc aaacattgtt taatcgtatg ttgcatatca gggctcaaat ggaattgggc 45781 aaaagaagta ggtattcatt caaatgagtc agctcatatt ttaggaagtc gagtcactaa agatgggaaa 45851 ttagtgattg acggagtttc taaacgggca gaagacttgc ttggtggcca cgacgaattc ttccttatca 45921 ctaacattga aactcttcgc gatgctgtgt tcattaaata cttaaatgaa ctgacaaaaa gcggagaaat 45991 tggaatggtt attattgacg agattcacaa gtgtaagaac ccttcaagta agcaaggggc ttcaattcaa 46061 aagctccaaa gttattacaa gatgggactt acaggaactc ctctaatgaa taacccaatc gatgtattca 46131 atgttatgaa gtggctaggg gcggaacatc atacactgac tcagttcaaa gagcgatact gtatcgtcga 46201 ccagttcaat caaatcactg gatatcgaaa tctagctgaa cttcgcgagc ttgtcaacga ctacatgctt 46271 agaagaacga aggaagaagt tttagacctg cctgaaaaga ttcgagtcac agagtatgtc gacatgaact 46341 cgaaacagtc aaaaatctat aaggaagttt tgactaaact tgttcaagaa atagataaag tcaagctcat 46411 gcctaaccct ctagccgaaa cgattcgact tcgacaagcg actggaaatc cttcgatttt aactactcaa 46481 gatgtcaagt cttgcaagtt cgaaagatgt atcgaaattg tcgaggaatg tatccagcaa ggaaagtcct 46551 gcgtgatatt tagcaattgg gaaaaggtta ttgaacctct tgctaagata ctttcgaaga cagtcaaatg 46621 caacctggta acaggagaaa ccgcagataa gttcaacgaa attgaagaat ttatgaatca cagaaaggct 46691 tctgttattt taggaactat aggtgcgcta ggaacaggat ttactttgac gaaagcggat acggttattt 46761 tcttagatag tccgtggaca cgcgcagaaa aggaccaagc cgaagatagg tgtcatagaa ttggcgca 46831 aagttctgtc actatctaca cgcttgtcgc caaaggtact gttgacgaac gtatagaaga cctta.ttgaa 46901 cggaaaggag aattagcaga ttatatcgta gatggtaagc ctatgaaatc taaaattggt aaccttttcg 46971 atatcctgct taaatagaat gaaaactatc tccatattaa ggaaagacac taaaaggaag ccggacagga 47041 acggaagaaa aactgcactc gaactagctc aagagattga tatgtcacct agtgagttag cagagctcct 47111 tcaaattcct gaaaggacgg caaccagaat tttaaaactc gacaaactgc tcaacaaaga gcaatgctca 47181 ataatagaaa ggtatataaa tgaaattcac tgaaggaaaa aattggtata aagttggaga gatatgtcaa 47251 atgttgaacc gctctctatc tacgattaat gtttggtatg aagcaaaaga cttcgCtgaa gaaaataaca WO 00/32825 PCT/IB99/02040 357 47321 ttcacttccc gtttgttctt cctgaaccta gaacagacct tgaccatcgt ggttctcgat tctgggatga 47391 cgaaggcgtg aacaaaCtca aaCgatttag ggacaaccta atgcgcggtg acttggcatt ctacactcga 47461 actcttgtag ggaaaactga aagggaagca attcaagaag atgctaaagc atttaaacgt gaacatggat 47531 tggagaatta aatgaaattt gaagatgaaa aacagttcat cgctgcaatt gaagaagccg gtgaattaaa 47601 tgctaccaaa ggcgacatgg agaaacaagt caaaagtctt cgtgatgctc taaaagagta catgaaagaa 47671 aatgacattg aatctgctca aggtaagcac ttttctgcta ccttctacac gacagagcgc tcaactatgg 47741 acgaagaacg cttgaaagaa attatcgaaa aattagttga cgaagccgag acggaagaaa tgtgtgaaaa 47811 actttcaggg cttatcgaat acaagcctgt catcaatacg aaacttctcg aggatatgat ttatcacggc 47881 gagattgacc aagaagcaat tcttccagca gttgtcattt ctgttacaga aggcattcgt tttggaaagg 47951 ctaaaattta gcgatatttt tggttctgcg acgtttttag ggttagcaga atccaatcac accacttgcg 48021 caggcaaccg ctgtctgcgt taattttaga aggttaatat tataccataa ggaggagata agtggcaagg 48091 caaagaatag gcaattcagg aaagcctaaa aatgaaattg aactaacatt caaagacaag cctaaaactc 48161 gttctacctt attcaagaag gacgtggcaa caggtctttc aaaagtcgag catgattatt ttcaaatagt 48231 tgaagcactt aacggaaaac aattcgaacc taatatgaag caggtgtcat ctttctttat agttcagtat 48301 gaatttattt tcaatattaa gtgcatcgat tataactggt tcaacttttc gagcactatg aaaaatgttc 48371 gaacttattt aaacattgag tcgaacattg aactttgtcg atttttagct gaaagttttg ttaaatatga 48441 aaatgttcga aaaagattga acctaagcga aaggttcata acggtctcga ctttcaaaag agcctggatt 48511 ttggacgaac tcgaaggaaa aacgggttca aaattcgaag gattttatta gtttagtaga ctatttttag 48581 attttttaaa atgtggttta caaaatgacc tcaataggcg tataatttat caatcttgat tctttcgggc 48651 cggtatatat acaccaataa tcgagaaata ataaattata gtatcgaaaa tataaaaagg agaaaagttg 48721 gaaaatttag ctgatagaat atggaagaaa aagttaaatg accttttcga gagaagtggg ctacctcaaa 48791 agtatttcga acctcaagtg ttagtcgaac gaaaagccga caaggaatgt tgggaatggc tagaagctgt 48861 tcgagcaaat atagtcgaag aagttcgaaa cggtcttagc attgttattg cttcgaatac tgtcgggaat 48931 gggaaaacta gctgggcggt tcgacttttg caacqctatt tagcagaaac tgcacttgac ggaagaattg 49001 ttgagaaagg aatgtttgta gtgtcagctc aactattgac tgagttcggc gactataatt attttcaaac 49071 catgcaagaa tttctcgaac gtttcgagcg ccttaagact tgtgagctat tagtcataga cgaaataggt 49141 ggaggttcct taaccaaggc ctcttatcct tatctgtatg acttggttaa ttatagggtt gacaataact 49211 tgtcgactat ttatacgact aattatactg acgatgaaat tattgacctt ttaggccaaa ggctttatag 49281 tcgtatatat gatacttcag tggttctaga ttttcaggca agcaatgtaa gaggattgga ggtaagcgaa 49351 attgaatcat agatatagta acatcacaac tatttttctt tggcagattg tctttctttg tatttgctgc 49421 gcggtgtcct attgtgcagg agtgcataat gagcgagagt ctcaagataa ggtgattcaa agttataagc 49491 agaaagaaaa gtcagccgtc tacttgacag tcgatagttc aggagcttgg ctaggaagtg ctccgggagc 49561 caaggaaagt cctctctaca atgaaaaggg acagcatgta ggaaaattga aagaggtggg agagtgatac 49631 agcttcaagi cttaaataaa gttctcgaag aaaagagctt atccatttta gaaaataatg gaattgacca 49701 agaatacttc acggattatt tagacgagta tcaatttatt caagaacact tttcgagata tggaagagtt 49771 ccggacgacg aaactattct cgaccatttt cctggattcg aatttttcga aattggcgaa actgatgaat 49841 accttatcga caagctaaaa gaggagcatc tatataattc acttgttcca attttaacgg aagcggctga 49911 ggacattcaa gtagatagta acattgcgat tgcgaatata attccaaaac tagaagaact tttcaatcgc 49981 tctaaattcg taggcggact agacattgct cgaaatgcta aacttcgact agactgggcg aatactatta 50051 gaaaccatga cggtgaaaga cttggaatat cgacagggtt tgaactattg gacgacgtgc ttggaggctt 50121 acttcctggt gaggatttga ttgtcataat ggctcgacct ggacaaggta agtcgtggac tattgataaa 50191 atgcttgcaa ctgcttggaa gaacgggcat gatgtccttc tatatagcgg ggaaatgagt gaaatgcaag 50261 ttggtgctcg tatagataCt attctttcga atgttagcat caattcaatt accaaaggga tttggaacga 50331 ccatcagttc gaaaaatatg aggaccatat tcaagcaatg actgaggctg aaaattccct tgtggtagtc 50401 acgcccttta tgattggagg aaagaacctt acccctgcaa ttttagatag catgatatct aaatatagac 50471 catctgtggc ggggattgac cagctttcac tcatgagcga gtcttatcca agcagggagc agaagcgaat 50541 ccagtacgcc aacatcacca tggacctata taagatttct gctaaatatg gaattcctat tgtgcttaat 50611 gtccaagcag ggcgttcggC taaaactgaa ggcgCtgaaa gtatggaact agaacatata gcagaaagtg 50681 atggagtagg tcaaaatgct agcagagtta tcgctatgaa gcgtgacgaa aaatccggca acttgaact 50751 atctgtcgtt aaaaaccgat atggcgaaga ccgaaaaatc atcgaatata tgtgggacgt tgaaactgga 50821 acctatactc ttataggatt caaagaggaa ggcgaagaag gaactgaaaa aggcgaaagc tctccattga 50891 aagcaaaagc ctctaggtcg actgctcgtc ttcgaagtaa ggttacaagg gaaggagttg aagcattttg 50961 atgaaagtaa atggtcttca aattgaagcg actcctgaac aaataattga aaaactttcg agacaacttg 51031 aagacgaagg aacattcatt tttagacgaa ctaagtcgct tggaagcaac tatcaattct catgcccgtt 51101 tcatgcagga gggactgaaa agcatccctc ttgtggcatg agtagaaatc cttcttattc aggaagtaag 51171 gtgacggaag ctggaacggt tcactgtttc acttgcggct acacttcagg actaactgaa ttcgtctcga 51241 atgtattagg tcgaaacgat ggagggttct atggaaacca gtggctgaaa aggaattttg gaacatctag 51311 cgaagtagtt aggcaaggcg tcagccctga agcgtttcga agaaatggga gaactgaaaa agtcgagcat 51381 aaaatcattc ctgaagagga acttgataaa taccggttta ttcatcctta tatgtatgaa cggaaattga 51451 cggacgagct catcgagatg tttgatgtag gttatgacaa actgcatgat tgcatcacct ttccagtacg 51521 gaacctcaag ggcgaaacag tattcttcaa ccgtcgaagt gttcgttcta agtttcacca gtacggtgaa 51591 gatgacccta aaacggaatt tctttatggc caatatgagc ttgtagcatt tcgagactat tttgaaaaac 51661 ctattagtca agtattcgtg actgagtctg ttatcaactg cttgactctt tggtcaaga agattccagc 51731 agtcgctctt atgggagtag gtggaggaaa tcaaatcaat ttactaaaac gacttcctta tagaaatatt 51801 gttctagcac ttgaccctga taacgctggg cagacagcgc aggaaaaact ctaccgacag ttaaagcgaa 51871 gcaaggtcgt tagatttttg aactacccta aagagttcta tgataataag tgggatataa acgaccatcc 51941 ggaattatta aattttaatg atttagtctt gtagaaattc atttattatc gtataataaa gttagaaaat 52011 tttaaaaaga ggtcatatca atatgaaaga agcgaataga ctagtttcta gctatgtagg attcgaatgc 52081 tggactgacg aagaatgtat caggaacttt gaactagacc ctgatatgtc aattgcgtct gattatca= 52151 gttattttgg gatgctttat tcctatgcaa aaaggtttaa atgcttatct cgacatgaca ttgaaagcat 52221 tgcattcgag actatttcaa aatgtttggC aacgttcaaa tcaaaccaag gggccaagtt ttcaacttac 52291 cttacaagac tcttcaagaa tagaatagtc ttagaatata ggtacctaaa tgcaccttcc atgaatcgaa 52361 attggtatgt agaagtgacg ttcgatagcg tttcgacaaa tgaagaaggc gacgatttta gtatcctatc 52431 gacagttggc tattgtgaag actacggaaa aattgaaatt gaagcaagtc ttgacttcat gacgctttct 52501 aatacagagt atgcttatat Ctcgtctgtc attcaaaacg gtccttcagt aagcgacgca gaaattgcgc 52571 gtgaaattgg agtaagcagg tCtgCtatta gtcagtctaa gaagtcacta aaaaataaat taaaagattt WO 00/32825 PCT/IB99/02040 358 52641 tatataactg gtttacaaat cacgtgaatt tcgtgtatat tatatatgaa aggacaaact ttgaaacctt 52711 aaaaacttca aaaatctttc aaccattaaa aacttataaa ggagaatcga tatgggaaaa gtatcaattc 52781 aaaaatcagg aacatttagc tcagggtcta ataacgagtt tttcacactc gctgaccacg gtgacagcgc 52851 aattgtcact ctattgtatg atgacccgga aggcgaagac atggattatt tcgtagtcca cgaagcagac 52921 gttgacggtc gtcgacgcta tatcaattgc aatgctattg gcgaagacgg ggaaacagtc catcctgata 52991 attgtccatt atgccaaaac ggattccctc gtattgaaaa actatttctt caactttaca accatgatac 53061 gggaaaagtt gaaacatggg accgaggccg ttcttatgtt caaaagattg ttacatttat caataaatat 53131 ggaagccttg tgactcagcc ttttgaaatt attcgttcag gagctaaagg tgaccaacga actacttatg 53201 aattccttcc agagcgtccg gaagacagtg ctactcttga agattttcca gaaaagagcg aacttcttgg 53271 aactctaatt ttagacctcg acgaagacca aatgtttgac gtggttgacg gcaagttcac tcttcaagaa 53341 gagcgttctt caagtcgttc aaattcacgt agaggagcat ctcctgcgcc tagacgaggt tccggtcgag 53411 aatcttcaca aggtcgaaca gctgaaagaa ctccttcagt tagtcgaaga actcctccaa cacgaggtcg 53481 aggattctaa catgagggcg cgagccctct ttattattga ttaagaaagg gaaaataatg gcacaaaaag 53551 gactctttgg tgcaaagcct cgttctagca agaagaacga tgctcagtta cttgctcaac ggaaaaacag 53621 gaagcctgca gttgaggtta cttacatttc aggaaacgct ctaaaggacg cagttgctag agctcgtact 53691 ctttcaacta ggattcttgg acacgttctt gatagacttg agttaatcac tgaggaagca aaactcgagc 53761 agtatgtaga caaaatgatt gaagacggaa taggttctat tgacgtagaa actgatggac tcgatactat 53831 tcacgatgag ctggcaggag tctgcttgta ctcacctagt caaaaaggaa tctatgctcc tgtcaatcat 53901 gttagcaata tgacgaagat gcgaattaag aatcaaattt ctcctgagtt catgaagaaa atgcttcaac 53971 ggattgtaga ttcaggaatt cctgtcatct atcataattc gaaatttgac atgaaatcga tttattggcg 54041 actcggcgtc aaaatgaatg agccagcgtg ggatacatat ttagccgcaa tgcttttaaa tgaaaacgag 54111 tctcacagct tgaaaagtct tcactctaaa tatgttagga acgaagaaaa cgcagaggtt gcaaaattta 54181 atgacttatt taaaggaatt ccttttagtt taattcctcc tgatgttgcc tatatgtatg cggcctatga 54251 ccctttgcaa actttcgaac tctatgaatt tcaagaacaa tacttgactc Caggaactga acaatgtgaa 54321 gaatataacc tggaaaaagt ctcatgggtt cttcataata ttgagatgcc tctaattaaa gttctcttcg 54391 acatggaagt ctacggtgtc gacttagacc aagataagct ggcagaaatt agagaacagt ttactgccaa 54461 tatgaacgag gctgagcaag agtttcaaca gcttgtcagc gaatggcagc ctgaaattga agaacttcga 54531 caaactaatt tccagagcta tcaaaaactc gaaatggatg caagaggtcg agtgacggta agcatttcca 54601 gtcctactca attagcaatt ctgttttatg atatcatggg attgaaaagt cctgaaaggg ataaacctag 54671 aggaacaggc gaaagtattg tcgagcattt tgataacgat atctcaaaag cacttttgaa atatagaaaa 54741 tatgcaaaat tagtttcgac ctatacaaca cttgaccaac accttgcaaa gcctgacaat cgaattcaca 54811 ctacattcaa acagtacgga gctaagacag ggcgtatgtc aagtgagaat cctaacttac agaatattcc 54881 ttctcgcggt gagggtgcag tagttcgaca aatctttgca gccagtgaag ggcattacat tattggtagt 54951 gactactctc aacaagaacc tcgttcattg gcggaattaa gtggcgacga aagtatgcga catgcttacg 55021 aacaaaacct ggacctatat tcagttatcg gttcgaaact ttatggtgtt ccctatgaag agtgtttaga 55091 gttctatccc gacggaacga ctaacaagga aggaaaactt cgaagaaatt ctgtcaagtc cgttctttta 55161 ggtcttatgt acggccgcgg ggctaactca atcgctgagc agatgaatgt atctgtcaaa gaagcgaata 55231 aggttattga agatttcttc accgagttcc ctaaagtggc agactatatc atattcgttc aacagcaggc 55301 gcaggacttg ggatatgttc aaacagctac cggtcgaaga agaaggcttc ctgatatgag tcttcctgaa 55371 tacgagttcg agtatatcga cgctagcaag aacgaagatt tcgacccctt taactttgac gcagaccaac 55441 agatggacga tactgttcct gaacatatta tcgaaaaata ttgggcccag ctagatagag cctggggatt 55511 taagaagaag caagaaatta aagaccaggc aaaagccgaa ggaattctta ttaaggataa cggaggcaag 55581 atagctgatg ctcagcgcca atgtttgaac tcagttattc aaggaacggc agccgacatg actaagtacg 55651 caatgattaa ggtacacaat gacgctgaat tgaaagaatt aggattccat ttaatgattc cagttcacga 55721 tgagttacta ggtgaggttc ctatcaagaa cgcaaaacgg ggagcagaaa gttgacaga agttatgatt 55791 gaagcagcca aggacattat tagtcttcca atgaaatgtg accccagtat agtagaaaga tggtatggtg 55861 aagaaattga aatctaaaat ctattcagtt gcatatataa ttctagtagt tattgcgaac cttgtgacaa 55931 tttatttcga acctttaaat gtgaaaggaa ttttaattcc tccaagcagt tggtttatgg gattcacttt 56001 cctgcttata aatctaataa gcaagtacga gaagccaaaa tttgcaggtt ctttgatatg ggtagggtta 56071 ttccttacct cgttgatttg ctttatgcaa aacctaccac aatcgcttgt cgtggcttca ggagttgcat 56141 tttggataag tcaaaaagca agtgtcttta tattcgacaa gctctcgaat aaattagact cgaagattgc 56211 aaatgctttg tctagcaaca tcggttctat tatagacgca accatatgga tttcattagg actgagtcct 56281 cttggaattg gaacggttgc atatatagat attccgtcag ccgtactagg ccaagttcta gttcagttta 56351 tcttgcagtc aattgcttcg agatatttga aaaagtagtc aggaaaattc ctgattatct tgcagtcaat 56421 tgcttcgaga tatttgaaaa agtagtcagg aaaattcctg attatttttt ttacaaaaac gcttgacttt 56491 attcattcat tattat WO 00/32825 PCT/IB99/02040 359 Table 29 Phage dpi ORFs list nb Name Frame Position Size Key words 1 dpORFO1 2 36698..40390 1230 Putative tail; 2 dp1ORFOO2 1 32386..35835 1149 Tail; 3 dp1ORFOO3 3 53538..55877 779 DNA polymerase ; 4 dplORFOO4 __ 3 40401..42440 679 Minor structural: 5 dpl1ORFOO 1 23674..25434 586 6 dpliORFOO6 2 45296..46987 563 SWI/SNE Helicase; 7 dpIORFOO7 3 22230..23621 463 Terminase; 8 dplORFO8 1 49624..50961 445 DNAb Helicase: 9 dplORFOO9 2 13160..14404 414 10 dp1ORFOO 2 8699..9859 386 RecA; 11 dpORFO1I 3 28017..29096 359 Major head; 12 dplORF012 3 5346.6419 357 1DNA po. III beta; 13 dpi ORFi13 3 10215.11240 341 DNA pol. III gamma and tau; 14 dplORF014 3 50961..51974 337 DNA pnmase; 15 dplORF015i _ 1 3793..4728 311 16 dpliORFl6 3 43413..44303 296 Amidase; 17 dpIORF017 1 11242..12081 279 18 dpIORFli8 3 35847..36686 279 19 1 dpIORF19 2 12161.12967 268 20 dpIO 02R0 1 1864..2658 264 exsD; Coenzyme P00; 21 dplORF02l 2 2504..3295 263 GTP cyclohydrolase; 22 dplORFO22 2 30896..31675 259 23 dpIlORF23 2 6419..7195 258 24 dplORF025 -1 18026..18778 250 25 dpiORFO24 3 25992..26738 248 26 dplORF026 2 21512..22252 246 27 dpIORFi27 1 52762..53490 242 28 dplORF028 3 44595..45299 234 29 dplORF029 2 662..1348 228 exsB: 30 dplORF031 3 26943..27611 222 31 dp1ORF030 -2 19423..20088 221 32 dplORF032 1 52033..52647 204 33 dplORF033 2 1 7670..8239 189 __________________________ 34 dplORF035 -1 16859..17425 188 35 dpi 0RF036 ~1 48808..49362 184 DNAc replication; 36 dpi 0RF037 1 55855..56388 177 ________________________ 37 dplORF034 2 131..652 173 38 dplORF038 3 1350..1871 173 exsC; 6-pyruvoyltetrahydropterin; 39 1dplORFO39 3 3306..3803 165 Citrulline biosynthesis: 40 dpiO 0F040 1 7192..7683 163 41 dpi ORF041 3 8208..8699 163 dUTPase; 42 dplORFO42 1 48082..48561 159 43 dplORF043 1 31699..32154 151 44 dpIORF044 -1 25211..25666 151 45 dplORFO45 2 25340..25777 145 46 1dplORFO46 3 42774..43202 142 47 dplORFO47 1 147542..47961 139 __________________________ 48 dplORFO48 -3 116308..16709 133 49 dplORF049 -3 43620.44018 132 50 dplORFO5O 3 15081..15476 131 51 dplORFO51 2 29765..30154 129 52 dplORF053 -3 49917..50300 127 53 1dplORF052 3 30516..30893 125 54 dplORF054 2 14423..14800 125 55 dpIORF055 3 127627..28004 125 56 dplORF056 -3 18780..19151 123 _________________________ 57 dpi 0RF057 1 9859..10218 119 58 dplORF058 3 15633..15989 118 59 dplORF059 1 30154..30507 117 60 dplORF06O -2 37717..38070 117 161 1dplQRF062 -3 144940..45284 1114 ______________________ 62 dplORFO63 1 47200..47541 113 63 dplORFO64 2 29108..29449 113 WO 00/32825 PCT/I B99102040 360 64 dplORFO66 -3 28566..28898 J 110 65 dplORF067 -1 4475..45061 108 66 dpOF6 3 29451..29768 105 67 dplORF069 -3 20094..20411 I 105 68 dplORFO61 -3 19161..19475 1 104 69 dplORF070 1 15973..16284 1 103 70 1dplORF071 3 138904..39209 101 71 dplORF072 -2 150749..51045 98 ________________________ 72 dplORF073 3 14262..14555 97 _________________________ 73 dplORF074 3 32298..32591 97 _____________________ 74 dplORF075 -1 22154..22447 97 _____________________ 75 dplORF076 -1 5435..5728 97 76 dplORF077 1 14800..15084 94 77 1dplORFO79 -3 35007..35288 93 1 78 dplORF081 -3 155188..55466 92 ________________________ 79 dplORF103 2 49352..49627 91 80 dplORF080 1 42490..42759 89 81 dplORF082 1 44728..44994 88 82 dplORF083 -1 35720..35974 84 83 dp1ORFO65 -3 51246..51497 83 84 1dplORF085 -3 10602..10847 81 85 d1OF 8 7. -2 29794..30036 80 86 dplORF088 3 5040..5279 79 87 dplQRF089 -2 12256..12495 79 88 dplORF273 3 56256..56486 76 89 dplORF078 -3 17280..17507 75 90 dplORF090 1 27037..27261 74 91 1dplORF091 1 43189..43413 74 Holin; 92 dpOF9 3 46989..47213 74 93 dplORF093 -2 45538..45756 72 94 dplORF095 3 8877..9089 70 95 dplORFO96 -1 46469..46681 70 96 dplORFO97 -1 38888..39100 70 97 dplORFO98 1 43627..43836 69 98 1dplORFO99 3 38298..38507 69 99 dplORF100 1I 1597.1803 68 100 dplqRFf101 2 19220..19426 68 101 dplORF094 1 8281..8484 67 102 dplORFlO2 2 4034..4237 67 103 dplORF1O4 -1 21224..21427 67 104 dplORF1O5 -2 1828..2028 66 105 1dplORF1O6 -3 10329..10529 66 ________________________ 106 dp1ORF1O8 -1 149250..49447 65 ________________________ 107 dpI 0RF109 -2 31435..31632 65 ________________________ 108 dplOR11 1 16444..16638 64 109 dplORF111 1 28657..28851 64 110 dplORFll3 -2 17521..17715 64 i11 dplORFO84 1 15445..15636 63 112 1dpIORF114 2 52952..53143 63 113 dplORF115 -3 5151..5342 63 114 dplORF116 -1 20474..20662 62 115 dplORF117 -3 24492..24680 62 116 dplORF1l8 2 15023..15208 61 117 dplORF119 2 41054..41239 61 _____________________ 118 dplORF12O -1 28387..28569 60 ______________________ 119 1dplORF121 3 39222..39404 60 120 dplORF122 -1 40220..40402 60 1 121 dplORF123 -2 21145..21327 60 122 dplORF124 -3 17712..17891 59 123 dplORF125 -3 49740..49916 58 124 dplORFl26 -3 15960..16136 58 125 dplORF127 -3 13335..13511 58 126 dpjF128. 1 4852..5025 57 127 dplORF129 2 25133..25306 57 1 128 dplORF130 -1 16619..16789 56 129 dplORF13l 1 43846..44013 55 130 dplORF132 -1 15137..15304 55 131 dplORF133 -2 7900..8061 53 __________________________ 132 dplORF135 3 780..938 52 ________________________ 133 dplORF136 -1 55094..55252 52 ________________________ 134 dplORF137 -2 136988..37146 52 1________________________ WO 00/32825 PCT/I B99/02040 ,61 135 dplRF38 -3 30504..30662 f 52 _____________________ 136 dplORF139 -3 11934.12092 52 I________________________ 137 dplORF140 3 20562..20717 51 ________________________ 138 dplORF141 -1 42767..42922 51 139 dplORF142 -3 31743..31898 51 140 dplORF143 -3 7410..7565 51 141 1dplORF144 1_ 1 36517..36669 50 142 dplORF145 1 42067..42219 50 143 dpliRF146 1 51484..51636 50 144 dplORF147 1 55207..55359 50 145 dplORF148 -1 28484..28636 50 146 dplORF150 -3 15033..15185 50 147 dplORF134 -2 349..498 49 148 dplORF151 1 28027..28176 49 _____________________ 149 dplORF152 __1 42235..42384 49 150 dplORF153 __2 22307..22456 49 151 dplORF086 2 52760..52906 48 152 dpOR154 2 18446..18592 48 153 dplORF155 __3 13512..13658 48 154 dplORFlS6 3 18777..18923 48 155 dplORF157 -2 13135..13281 48 156 dplORF158 -3 40581..40727 48 ______________________ 157 dplORF159 -3 30225..30371 48 _______________________ 158 dplORF149 -3 26331..26474 47 _________________________ 159 dplORFl60 _ 2 41324..41467 47 _____________________ 160 dpliEE161. 2 52175..52318 47 _____________________ 161 dplORF162 1 3 13020..13163 47 162 dplORF163 3 40224..40367 47 163 dplORFl64 -2 6553..6696 47 164 dplORF165 -3 50361..50504 47 _________________________ 165 dplORFl66 -3 23376..23519 47 166 dplORFl67 3 1008..1148 46 167 dpi 0RF168 -2 54205..54345 46 168 dplORF169 1 -2 45814..45954 46 ________________________ 169 dplORF170 -2 27460..27600 46 170 dpi ORF171 -3 47538..47678 46 171 dplORF172 -1 10325..10462 45 172 dplORF173 -2 32023..32160 45 173 dplORF174 -2 29629..29766 45 174 dplORF175 -2 15511..15648 45 175 dplORFl76 1 -3 42894..43031 45 176 dplORF177 -3 19800..19937 45 177 dplORF178 -3 11787..11924 45 178 dplORF112 2 32207..32341 44 179 dplORF179 3 56058..56192 44 180 dplORF180 -1 41042..41176 44 181 dplORF181 -1 12992..13126 44 182 dplORFl82 1 -2 45235..45369 44 183 dplORF183 -2 13762..13896 44 184 dplORF184 -3 53196..53330 44 185 dplORF185 1 22522..222653 43 186 dplOR186. 2 21272..21403 43 187 dplORF187 2 3441 5..34546 43 188 dplORF188 2 35609..35740 43 189 dplORF189 1 2 42587..42718 43 190 dpOR190 3 39786..39917 43 191 dplORF191 -1 40865..40996 43 192 dplORF192 -1 2789..2920 43 193 dplORF193 -2 42325..42456 43 194 dplORF194 -2 40153..40284 43 195 dplORF195 -3 42453..42584 43 196 dpIORF196 -3 11142..11273 43 ____________________ 197 dplORF107 1 10750..10878 42 ________________________ 198 dplORF197 2 7484..7612 42 1_____________________ 199 dplORF198 2 24119..24247 42 _____________________ 200 dplORF199 -1 15614..15742 42 201 dplORF200 -3 47715..47843 42 ________________________ 202 dplORF201 1 38569..38694 41 ________________________ 203 dplORF202 2 44483.44608 41 ________________________ 204 dpI 0RF203 -3 22656..22781 1 41 _______________________ 25 dplORF204 1 1471..1593 1 40 _______________________ WO 00/32825 PCT/IB99/02040 362 206 dplORF2O5 1 8524..8646 40 207 dplORF2O6 1 1 19855..19977 40 208 dplORF27 i 1 27502..27624 40 209 dplORF2O8 1i 2 47279..47401 40 210 dplORF209 1 3 29784..29906 40 211 dplORF210 -1 52955..53077 40 212 dplORF211 -1 20837..20959 1 40 213 dplORF212 -2 52861..52983 40 214 dp1ORF213 -2 30169..30291 L 40 215 dplORF24 -2 24151.24273 40 216 dplORF2l5 -3 35700..35822 40 217 dplpO 21 -3 32727..32849 40 218 dplORF2l 7 1 23443..23562 39 219 dplORF218 3 22029..22148 39 220 dplORF2l9 -1 51269..51388 39 221 dpIORF22O -1 6215..6334 39 222 dp1ORF22l 1 43507..43623 38 223 dplORF222 [ 3 13212.13328 38 224 dplORF223 3 14055..14171 38 225 dplORF224 -1 13505..13621 38 226 1 dplORF225 -2 32875..32991 38 227 dplORF226 -2 25075..25191 38 228 dplORF227 -2 22999..23115 38 229 dpNORF228 1 10450..10563 37 230 dp1ORF229 1 27634..27747 37 231 dpi iRF230 2 50723.50836 37 232 dplORF23 -2 30958..31071 37 233 1 dplORF232 -2 29272..29385 37 234 dpORS233 -3 52779..52892 37 235 dplORF234 1 36253..36363 36 236 dpiORF23S 2 32768..32878 36 237 dplORF236 -1 37418..37528 36 238 dpi lRF237 -1 1568..1678 36 239 dplORF238 -3 1191..1301 36 240 1dpilORF239 1 26521..26628 35 241 d SEORF24i 1 41893.42000 35 242 dplORF24l -1 46913.47020 35 243 dpORF242 -1 41231.41338 35 244 dp1ORF243 -2 51199..51306 35 245 dp10RF244 -3 26976..27083 35 246 dplORF245 -3 6171..6278 35 247 dpIlSRF246 -3 2724..2831 35 248 dplORF247 1 29641.29745 34 249 dp1ORF248 1 53560.53664 34 250 dplORF249 2 2012..2116 34 251 dplORF250 2 23837..23941 34 252 dplORF251 -1 39101.39205 34 253 dplORF252 -2 54667.54771 34 254 dplORF253 -3 56151..56255 34 255 dplORF254 -3 48375..48479 34 256 dplORF255 -3 9468..9572 34 257 dp1ORF256 1 15289..15390 33 258 dp1ORF2S7 1 28216..28317 33 259 dpORF2S8 1 44023..44124 33 260 dplORF259 2 4298..4399 33 261 dplORF26i 2 24746.24847 33 262 dplORF261 3 258..389 33 263 dplORF262 3 9408.9509 33 264 dplOiF263 -1 26951.27052 33 265 dplORF264 -1 6038.6139 33 266 dp10RF265 -1 4700..4801 33 267 dplORF266 -2 50119..50220 33 268 dplORF267 -2 47266..47367 33 269 dp1ORF268 -2 12520..12621 33 270 dpORF269 1 -3 53733..53834 33 271 dplORF270 -3 50691..50792 33 272 dpiORF27l -3 19638.19739 33 273 dplORF272 -3 1455.1556 33 WO 00/32825 PCT/IB99/02040 363 Table 30 Predicted Dp-1 amino acid sequences dp1ORF001 36698 atgattgacaataatttacctatgagtccaattcctggcgaaattgttcaagtatatgaccaaaacttcaatctaattggagca 1 M I D N N L P M S P I P G E I V Q V Y D Q N F N L I G A 36782 agtgatgaaatctttagcaagcattacgaagacgaaattgtgactcgagctcgaggaaaagaaactttcacttttgaaagtatt 29 S D E I F S K H Y E D E I V T R A R G K E T F T F E S I 36866 gaaacctcatctatctatcaacacttaaaggttgaaaacattatccagtatggaggaagatggtttcgaattaaatatgctcag 57 E T S S I Y Q H L K V E N I I Q Y G G R W F R I K Y A Q 36950 gacgtagaagatgtcaaagggcttaccaagtttacctgctacgcattatggtatgaactagcagaaggcttgcctaggaagttg 85 D V E D V K G L T K F T C Y A L W Y E L A E G L P R K L 37034 aaacacgttgcttcttctgtaggcgctgtcgcgctagatattatcaaagacgcaggtgaatgggttcgactagtttgtcctcct 113 K H V A S S V G A V A L D I I K D A G E W V R L V C P P 37118 gacggtgctaacaaacaagttcgaagcataacagccgcagaaaattcaatgctttggcatcttcgatatcttgcaaagcaatac 141 D G A N K Q V R S I T A A E N S M L W H L R Y L A K Q Y 37202 aatttagaattgacatttggttatgaagaaattatcaagcaagaggttagaattgttcaaaccgttgtatttcttcagccttat 169 N L E L T F G Y E E I I K Q E V R I V Q T V V F L Q P Y 37286 gtcgagtctaaagtagactttcctcttgtagttgaagagaatttgaaatatgtcactaggcaggaagattctcgaaacctgtgt 197 V E S K V D F P L V V E E N L K Y V T R Q E D S R N L C 37370 acggcttacaagttgacaggtaaaaaggaagaaggcagtcaagagcctttaacgtttgcttctatcaacaatggaagtgaatat 225 T A Y K L T G K K E E G S Q E P L T F A S I N N G S E Y 37454 ctcattgatgtttcgtggtttactacacgccacatgaagcctcgatatattgctaaatctaaaagcgacgaacattttagaatt 253 L I D V S W F T T R H M K P R Y I A K S K S D E H F R I 37538 aaagaaaatttgatgagtgctgcgcgtgcttatcttgacatctacagtcgcccactaattggatatgaggcttcagcggtcctt 281 K E N L M S A A R A Y L D I Y S R P L I G Y E A S A V L 37622 tataacaaggttcctgacttgcatcatactcaactaattgtcgacgaccattatgatgttatcgagtggcgaaagatatctgct 309 Y N K V P D L H H T Q L I V D D H Y D V I E W R K I S A 37706 cgaaaaattgactacgacgacctttcaaactctactatcattttccaagaccctcgaaaagacttgatggacttgctaaatgag 337 R K I D Y D D L S N S T I I F Q D P R K D L M D L L N E 37790 gacggcgaaggagtcctttcaggggaaactgtaaatgagtcccaagttgttattagatacgcagatgacattttagggactaat 365 D G E G V L S G E T V N E S Q V V I R Y A D D I L G T N 37874 tttaatgcagaatctgggaaatacattggtgtccttaatactaataagaaaccgagcgaattagttcctgacgactttacatgg 393 F N A E S G K Y I G V L N T N K K P S E L V P D D F T W 37958 attcgactagaaggtcctaaaggtgacgcaggtttaccgggagctcctgggcgtgatggagtcgacggtgtacctggaaagagc 421 I R L E G P K G D A G L P G A P G R D G V D G V P G K S 38042 ggagtagggatagcagatacagctatcacttatgctgtatccgtttccggaacgcaagagcctgaaaatggatggagcgaacaa 449 G V G I A D T A I T Y A V S V S G T Q E P E N G W S E Q 38126 gttcctgaactcataaaaggtcgattcttgtggactaaaacattttggagatatactgacggctcacatgaaactggatactcc 477 V P E L I K G R F L W T K T F W R Y T D G S H E T G Y S 38210 gttgcctatatagggcaagacggaaattccggaaaagacggaatcgcaggtaaggacggagtaggtatagccgcaactgaagtc 505 V A Y I G Q D G N S G K D G I A G K D G V G I A A T E V 38294 atgtatgcaagttcgccatctgctactgaagctccagctggtggatggtctacgcaagttcctaccgtcccaggtggtcagtat 533 M Y A S S P S A T E A P A G G W S T Q V P T V P G G Q Y 38378 ttatggactcgaacaagatggcgctacactgaccaaactgatgaaattggatattcagtttcaagaatgggcgagcagggtcct 561 L W T R T R W R Y T D Q T D E I G Y S V S R M G E Q G P 38462 aaaggtgacgcaggtcgtgacggtattgcaggaaagaacggaatagggttgaagtcaacttcagtttcttatggaattagtccc 589 K G D A G R D G I A G K N G I G L K S T S V S Y G I S P 38546 actgattctgcgattcctggagtatgggcttcacaagttccttctttaatcaaaggtcaatatctttggactcgaactatttgg 617 T D S A I P G V W A S Q V P S L I K G Q Y L W T R T I W 38630 acctataccgattcaactaccgaaacgggctatcaaaaaacctacattccaaaagacgggaatgacggtaaaaatggaattgct 645 T Y T D S T T E T G Y Q K T Y I P K D G N D G K N G I A 38714 ggtaaggatggggtaggaattaagtctacgaccattacctacgcaggctcaacctcaggaacagttgcgcctacttcaaattgg 673 G K D G V G I K S T T I T Y A G S T S G T V A P T S N W 38798 acttctgctattccaaatgttcaaccgggattcttcttgtggacgaaaactgtttggaactatactgatgacactagcgaaaca 701 T S A I P N V Q P G F F L W T K T V W N Y T D D T S E T 38882 ggttactcagtttccaagataggtgaaacaggtcctagaggagttcaaggtcttcaaggtcctcaagggcttcaaggaattcct 729 G Y S V S K I G E T G P R G V Q G L Q G P Q G L Q G I P 38966 ggacctgcaggagctgacggacgttcgcaatatactcacctcgctttctctaatagtccaaacggtgagggatttagtcatact 757 G P A G A D G R S Q Y T H L A F S N S P N G E G F S H T 39050 gacagcggacgagcatacgtcggtcagtatcaagatttcaatcccgtccattcaaaagaccctgcagcctatacatggacgaaa 785 D S G R A Y V G Q Y Q D F N P V H S K D P A A Y T W T K 39134 tggaaggggaatgacggagctcaagggatacccgggaagccaggcgcagacggtaagactaattatttccatatagcttacgct 813 W K G N D G A Q G I P G K P G A D G K T N Y F H I A Y A 39218 tcaagtgcagacggatcacgtgagttcagtttggaagataataatcaacaatatatgggttattactccgattatgaggaadca 841 S S A D G S R E F S L E D N N Q Q Y M G Y Y S D Y ~E-Q A 39302 gatagcagggatcgaactaagtatcgatggtttgaccgccttgccaatgttcaagtgggaggtcgaaacgagttccttaattct 869 D S R D R T K Y R W F D R L A N V Q V G G R N E F L N S 39386 ttatttgaatttggtttaaaacctcgctattctagttacaatctaatggacggacaagatcaaacgcaaggacagatatctgct 897 L F E F G L K P R Y S S Y N L M D G Q D Q T Q G Q I S A 39470 actattgacgaacgtcaacggttcaaaggtgctaactctttacgacttgactcaacatggaacggtaaaccgcagaaccaaaaa 925 T I D E R Q R F K G A N S L R L D S T W N G K P Q N Q K WO 00/32825 PCT/IB99/02040 364 39554 ctgaccttttctttaggaggagatacgcgattaggtactccaaccgagtggtctaatttagaaggtcgtatcagtttctgggct 953 L T F S L G G D T R L G T P T E W S N L E G R I S F W A 39638 aaggcctctaggaacggagtgagcttagctgcacggccgggttatcgtagtaacgtatttaccgcaaccttaaccgatcaatgg 981 K A S R N G V S L A A R P G Y R S N V F T A T L T D Q W 39722 aagttctacgattttaaattctttgacaaagttaattcaaattgtaccgctgaagcaattttccatgtattcactcaaagttgt 1009 K F Y D F K F F D K V N S N C T A E A I F H V F T Q S C 39806 tcagtgtggctcaatcatattaaaatcgaacttggtaatatctctactccttttagtgaagcagaggaagaccttaaatatcga 1037 S V W L N H I K I E L G N I S T P F S E A E E D L K Y R 39890 attgactcaaaagccgatcaaaagctaactaaccaacagttgacggcactcacggaaaaggctcaactacatgacgcagaactg 1065 I D S K A D Q K L T N Q Q L T A L T E K A Q L H D A E L 39974 aaagctaaggctacaatggagcagttaagtaacttagaaaaggcttatgaaggtagaatgaaagctaatgaagaagctatcaaa 1093 K A K A T M E Q L S N L E K A Y E G R M K A N E E A I K 40058 aaatcggaagccgacctaatcttagcggcaagtcgaattgaagctactatccaagaacttggcgggctacgggaactgaagaag 1121 K S E A D L I L A A S R I E A T I Q E L G G L R E L K K 40142 ttcgtcgacagttacatgagctcttctaatgaaggtctaattatcggtaagaacgacggtagctctaccattaaggtatcaagt 1149 F V D S Y M S S S N E G L I I G K N D G S S T I K V S S 40226 gaccgaatttctatgttctccgcagggaatgaagttatgtaccttacgcaagggttcattcacatcgataacgggatctttacc 1177 D R I S M F S A G N E V M Y L T Q G F I H I D N G I F T 40310 caatccattcaagtcggccgatttagaacggaacaatactcgtttaatccagacatgaacgtgattcggtatgtaggataa 40390 1205 Q S I Q V G R F R T E Q Y S F N P D M N V I R Y V G * dplORFOO2 32386 atggattttgggtcaattgcagcaaaaatgactttggatatctcaaacttcacaagtcaattaaatcttgctcaaagtcaagcg 1 M D F G S I A A K M T L D I S N F T S Q L N L A Q S Q A 32470 caacggctcgcactagagtcttcgaagtcctttcaaattggttctgctttaacaggattagggaaaggacttacgactgcggtt 29 Q R L A L E S S K S F Q I G S A L T G L G K G L T T A V 32554 acccttcctcttatgggatttgcagccgcctctattaaagtagggaatgaattccaagctcaaatgtcccgtgttcaagctatt 57 T L P L M G F A A A S I K V G N E F Q A Q M S R V Q A I 32638 gcaggagcgacagcggaagagcttggtagaatgaagactcaagcaatcgaccttggtgctaaaactgcttttagtgcaaaagag 85 A G A T A E E L G R M K T Q A I D L G A K T A F S A K E 32722 gcggctcaaggtatggaaaatctagcttcagccggtttccaggtaaatgaaatcatggacgctatgccaggggtacttgacctg 113 A A Q G M E N L A S A G F Q V N E I M D A M P G V L D L 32806 gctgccgtatctggaggagatgtggccgcgagctccgaggccatggctagttcacttcgagcctttggattagaggcaaaccag 141 A A V S G G D V A A S S E A M A S S L R A F G L E A N Q 32890 gcgggtcacgtggctgacgtatttgctcgagcagcagctgatacgaacgcagaaactagcgacatggcagaggcgatgaaatac 169 A G H V A D V F A R A A A D T N A E T S D M A E A M K Y 32974 gtcgcacccgttgctcactctatgggcttgagccttgaagaaacggctgcgtctattgggattatggccgacgccggtattaag 197 V A P V A H S M G L S L E E T A A S I G I M A D A G I K 33058 ggctcgcaagccggaaccacgcttagaggcgctctctcgcgtattgccaaacctacgaaagcgatggtcaaatcaatgcaggaa 225 G S Q A G T T L R G A L S R I A K P T K A M V K S M Q E 33142 ttaggagtttcgttctacgacgcgaacggaaacatgattccactaagagaacaaatcgctcaactgaaaacagctactgcagga 253 L G V S F Y D A N G N M I P L R E Q I A Q L K T A T A G 33226 ctaacacaagaggaacgaaatcgtcaccttgttaccttgtatggccaaaactcgttgtcaggtatgcttgcactattagacgca 281 L T Q E E R N R H L V T L Y G Q N S L S G M L A L L D A 33310 ggtcctgagaaattggataagatgaccaatgctctcgtgaactcggacggagctgctaaggaaatggcagaaactatgcaggac 309 G P E K L D K M T N A L V N S D G A A K E M A E T M Q D 33394 aaccttgctagtaaaatcgagcaaatgggaggagctttcgagtctgttgctattattgttcaacaaatccttgagcctgcactt 337 N L A S K I E Q M G G A F E S V A I I V Q Q I L E P A L 33478 gctaaaatcgtgggagcaatcacaaaagttctcgaagcattcgtaaatatgtcacctatcggtcaaaagatggttgtcatattc 365 A K I V G A I T K V L E A F V N M S P I G Q K M V V I F 33562 gcaggaatggttgcagcccttggaccactgcttctaattgcaggaatggtgatgacaactattgtcaagttaagaattgctatt 393 A G M V A A L G P L L L I A G M V M T T I V K L R I A I 33646 cagtttttaggtccagcatttatgggaacgatgggaaccattgcaggagttatagcaatattctatgtctggtcgccgtgttc 421 Q F L G P A F M G T M G T I A G V I A I F Y A L V A V F 33730 atgatagcctacacaaaatcggagagatttagaaactttatcaacagtcttgcgcctgctattaaagctgggtttggaggagcg 449 M I A Y T K S E R F R N F I N S L A P A I K A G F G G A 33814 ttggaatggctacttccacgactgaaagagttaggagaatggttacagaaggcaggcgagaaggcgaaagagttcggtcagtct 477 L E W L L P R L K E L G E W L Q K A G E K A K E F G Q S 33898 gtagggtctaaagtgtcaaaactgctcgaacagtttggaataagtatcggtcaggcaggaggctcgattggtcagttcattgga 505 V G S K V S K L L E Q F G I S I G Q A G G S I G Q F I G 33982 aatgttctcgaaaggctaggaggcgcatttggaaaagtaggaggagtcatttcaattgctgtttcacttgtaacaaaattcggt 533 N V L E R L G G A F G K V G G V I S I A V S L V T K F G 34066 ctcgcatttctagggattacaggaccactcgggattgctattagtctgttagtttcatttttgacagttgggtagaacaggt 561 L A F L G I T G P L G I A I S L L V S F L T A W A R T G 34150 gagttcaacgcagacggaattactcaagtattcgaaaacttgacaaacacaattcagtcgacggctgatttcatctctcaatac 589 E F N A D G I T Q V F E N L T N T I Q S T A D F I S Q Y 34234 cttccagtctttgtcgaaaaaggaactcaaattttagttaagattattgaaggaattgcatctgctgttcctcaagtagttgaa 617 L P V F V E K G T Q I L V K I I E G I A S A V P Q V V E 34318 gtgatttcacaagtcattgaaaatattgtgatgacaatttcgacagttatgcctcaattagtcgaagcaggaattaagiaCtt 645 V I S Q V I E N I V M T I S T V M P Q L V E A G I1~K1-I L 34402 gaagcgcttataaatggtcttgttcaatctcttcctactatcattcaagcagctgttcaaattatcactgcttattcaatggt 673 E A L I N G L V Q S L P T I I Q A A V Q I I T A L F N G 34486 cttgttcaggcacttcctacgcttattcaagcaggtcttcaaattttgtcagctctcataaacggactagttcaagcgcttccg 701 L V Q A L P T L I Q A G L Q I L S A L I N G L V Q A L P 34570 gcaattattcaagcagctgttcaaattatcatgtcgcttgttcaagcactaattgaaaacttgcctatgataatcgaagcagcg 729 A I I Q A A V Q I I M S L V Q A L I E N L P M I I E A A WO 00/32825 PCT/I B99/02040 365 34654 atgcagattataatgggtctagtcaacgcactgattgaaaatataggacctatcttagaagcagggattcaaattctaatggct 757 M Q I I M G L V N A L I E N I G P I L E A G I Q I L M A 34738 ttaatcgagggacttattcaagtgcttcctgaactaattacagcagcgattcaaatcattacttcactattagaagcaatcttg 785 L I E G L I Q V L P E L I T A A I Q I I T S L L E A I L 34822 tcgaaccttcctcaacttctagaagccggagttaaattgcttttatcacttcttcaagggttgctaaatatgcttcctcaacta 813 S N L P Q L L E A G V K L L L S L L Q G L L N M L P Q L 34906 attgcaggggctttgcaaatcatgatggcacttcttaaagcagttatcgacttcgtccctaaacttcttcaagcaggtgttcaa 841 I A G A L Q I M M A L L K A V I D F V P K L L Q A G V Q 34990 cttcttaaggcattgattcaaggtattgcttcacttctcggctcacttttatcgacagctggaaacatgctttcatcattagtt 869 L L K A L I Q G I A S L L G S L L S T A G N M L S S L V 35074 agcaagattgctagctttgtgggacagatggtttcaggaggtgcgaacctgattcgaaacttcattagtggtattgggtcaatg 897 S K I A S F V G Q M V S G G A N L I R N F I S G I G S M 35158 attggttcagctgtctctaaaattggcagcatgggaacttcaattgtttctaaggttactggattgctggacaaatggtaagc 925 I G S A V S K I G S M G T S I V S K V T G F A G Q M V S 35242 gcaggggtcaaccttgttcgaggatttatcaatggtatcagttccatggtaagttctgcggtaagtgcggcggctaatatggct 953 A G V N L V R G F I N G I S S M V S S A V S A A A N M A 35326 agcagtgcattaaatgccgttaagggattcttaggtattcactctccttcacgtgtcatggagcagatgggtatctatacgggt 981 S S A L N A V K G F L G I H S P S R V M E Q M G I Y T G 35410 caagggttcgtaaatggtattggtaacatgattcgaactacacgtgacaaggctaaagaaatggctgaaactgttactgaagct 1009 Q G F V N G I G N M I R T T R D K A K E M A E T V T E A 35494 ctcagcgacgtgaagatggatattcaagaaaatggagttatagaaaaggttaaatcagtttacgaaaagatggctgaccaactt 1037 L S D V K M D I Q E N G V I E K V K S V Y E K M A D Q L 35578 cctgaaactcttccagctcctgatttcgaagatgttcgtaaagcagccggttcgcctcgagtggattgttaatacaggaagt 1065 P E T L P A P D F E D V R K A A G S P R V D L F N T G S 35662 gacaaccctaaccaacctcagtcacaatctaaaaacaatcaaggcgagcaaaccgttgtcaacattggaacaatcgtagttcga 1093 D N P N Q P Q S Q S K N N Q G E Q T V V N I G T I V V R 35746 aacaatgacgacgttgacaaactgtcgagaggattgtataatagaagtaaagaaactctatcagggtttggtaacattgtaaca 1121 N N D D V D K L S R G L Y N R S K E T L S G F G N I V T 35830 ccgtaa 35835 1149 P * dplORFOO3 53538 atggcacaaaaaggactctttggtgcaaagcctcgttctagcaagaagaacgatgctcagttacttgctcaacggaaaaacagg 1 M A Q K G L F G A K P R S S K K N D A Q L L A Q R K N R 53622 aagcctgcagttgaggttacttacatttcaggaaacgctctaaaggacgcagttgctagagctcgtactctttcaactaggatt 29 K P A V E V T Y I S G N A L K D A V A R A R T L S T R I 53706 cttggacacgttcttgatagacttgagttaatcactgaggaagcaaaactcgagcagtatgtagacaaaatgattgaagacgga 57 L G H V L D R L E L I T E E A K L E Q Y V D K M I E D G 53790 ataggttctattgacgtagaaactgatggactcgatactattcacgatgagctggcaggagtctgcttgtactcacctagtcaa 85 I G S I D V E T D G L D T I H D E L A G V C L Y S P S Q 53874 aaaggaatctatgctcctgtcaatcatgttagcaatatgacgaagatgcgaattaagaatcaaatttctcctgagttcatgaag 113 K G I Y A P V N H V S N M T K M R I K N Q I S P E F M K 53958 aaaatgcttcaacggattgtagattcaggaattcctgtcatctatcataattcgaaatttgacatgaaatcgatttattggcga 141 K M L Q R I V D S G I P V I Y H N S K F D M K S I Y W R 54042 ctcggcgtcaaaatgaatgagccagcgtgggatacatatttagccgcaatgcttttaaatgaaaacgagtctcacagcttgaaa 169 L G V K M N E P A W D T Y L A A M L L N E N E S H S L K 54126 agtcttcactctaaatatgttaggaacgaagaaaacgcagaggttgcaaaatttaatgacttatttaaaggaattccttttagt 197 S L H S K Y V R N E E N A E V A K F N D L F K G I P F S 54210 ttaattcctcctgatgttgcctatatgtatgcggcctatgaccctttgcaaactttcgaactctatgaatttcaagaacaatac 225 L I P P D V A Y M Y A A Y D P L Q T F E L Y E F Q E Q Y 54294 ttgactccaggaactgaacaatgtgaagaatataacctggaaaaagtctcatgggttcttcataatattgagatgccttaatt 253 L T P G T E Q C E E Y N L E K V S W V L H N I E M P L I 54378 aaagttctcttcgacatggaagtctacggtgtcgacttagaccaagataagctggcagaaattagagaacagtttactgccaat 281 K V L F D M E V Y G V D L D Q D K L A E I R E Q F T A N 54462 atgaacgaggctgagcaagagtttcaacagcttgtcagcgaatggcagcctgaaattgaagaacttcgacaaactaatttccag 309 M N E A E Q E F Q Q L V S E W Q P E I E E L R Q T N F Q 54546 agctatcaaaaactcgaaatggatgcaagaggtcgagtgacggtaagcatttccagtcctactcaattagcaattctgttttat 337 S Y Q K L E M D A R G R V T V S I S S P T Q L A I L F Y 54630 gatatcatgggattgaaaagtcctgaaagggataaacctagaggaacaggcgaaagtattgtcgagcattttgataacgatatc 365 D I M G L K S P E R D K P R G T G E S I V E H F D N D I 54714 tcaaaagcacttttgaaatatagaaaatatgcaaaattagtttcgacctatacaacacttgaccaacaccttgcaaagcctgac 393 S K A L L K Y R K Y A K L V S T Y T T L D Q H L A K P D 54798 aatcgaattcacactacattcaaacagtacggagctaagacagggcgtatgtcaagtgagaatcctaacttacagaatattcct 421 N R I H T T F K Q Y G A K T G R M S S E N P N L Q N I P 54882 tctcgcggtgagggtgcagtagttcgacaaatctttgcagccagtgaagggcattacattattggtagtgactactctcaacaa 449 S R G E G A V V R Q I F A A S E G H Y I I G S D Y S Q Q 54966 gaacctcgttcattggcggaattaagtggcgacgaaagtatgcgacatgcttacgaacaaaacctggacctatattcagttatc 477 E P R S L A E L S G D E S M R H A Y E Q N L D L Y S V I 55050 ggttcgaaactttatggtgttccctatgaagagtgtttagagttctatcccgacggaacgactaacaaggaaggaaaacttcga 505 G S K L Y G V P Y E E C L E F Y P D G T T N K-E G K-.L R 55134 agaaattctgtcaagtccgttcttttaggtcttatgtacggccgcggggctaactcaatcgctgagcagatgaatgtatctgtc 533 R N S V K S V L L G L M Y G R G A N S I A E Q M N V S V 55218 aaagaagcgaataaggttattgaagatttcttcaccgagttccctaaagtggcagactatatcatattcgttcaacagcaggcg 561 K E A N K V I E D F F T E F P K V A D Y I I F V Q Q Q A 55302 caggacttgggatatgttcaaacagctaccggtcgaagaagaaggcttcctgatatgagtcttcctgaatacgagttcgagtat 589 Q D L G Y V Q T A T G R R R R L P D M S L P E Y E F E Y 55386 atcgacgctagcaagaacgaagatttcgacccctttaactttgacgcagaccaacagatggacgatactgttcctgaacatatt WO 00/32825 PCT/IB99/02040 366 617 I D A S K N E D F D P F N F D A D Q Q M D D T V P E H I 55470 atcgaaaaatattgggcccagctagatagagcctggggatttaagaagaagcaagaaattaaagaccaggcaaaagccgaagga 645 I E K Y W A Q L D R A W G F K K K Q E I K D Q A K A E G 55554 attcttattaaggataacggaggcaagatagctgatgctcagcgccaatgtttgaactcagttattcaaggaacggcagccgac 673 I L I K D N G G K I A D A Q R Q C L N S V I Q G T A A D 55638 atgactaagtacgcaatgattaaggtacacaatgacgctgaattgaaagaattaggattccatttaatgattccagttcacgat 701 M T K Y A M I K V H N D A E L K E L G F H L M I P V H D 55722 gagttactaggtgaggttcctatcaagaacgcaaaacggggagcagaaaggttgacagaagttatgattgaagcagccaaggac 729 E L L G E V P I K N A K R G A E R L T E V M I E A A K D 55806 attattagtcttccaatgaaatgtgaccccagtatagtagaaagatggtatggtgaagaaattgaaatctaa 55877 757 I I S L P M K C D P S I V E R W Y G E E I E I * dplORF004 40401 atgacaaaatttatcaactcatacggccctcttcacttgaacctttacgtcgaacaagttagtcaggacgtaacgaacaactcc 1 M T K F I N S Y G P L H L N L Y V E Q V S Q D V T N N S 40485 tcgcgagttagttggcgagctactgtcgaccgcgatggagcttatcgaacgtggacttatggaaatattagtaacctttccgta 29 S R V S W R A T V D R D G A Y R T W T Y G N I S N L S V 40569 tggttaaatggttcaagtgttcatagcagtcacccagactacgacacgtccggcgaagaggtaacgctcgcaagtggagaagtg 57 W L N G S S V H S S H P D Y D T S G E E V T L A S G E V 40653 actgttcctcacaatagtgacgggacaaagacaatgtccgtttgggcttcgtttgaccctaataacggcgttcacggaaatatc 85 T V P H N S D G T K T M S V W A S F D P N N G V H G N I 40737 actatctctactaattacactttagacagtattccaaggtctacacagatttctagttttgagggaaatcgaaatctaggatct 113 T I S T N Y T L D S I P R S T Q I S S F E G N R N L G S 40821 ttacatacggttatctttaaccgaaaagtgaactcttttacgcatcaagtttggtaccgagttttcggtagcgactggatagat 141 L H T V I F N R K V N S F T H Q V W Y R V F G S D W I D 40905 ttaggtaagaaccatactactagcgtatcctttacgccgtcactggacttagcaaggtacttacctaaatcaagttccggaaca 169 L G K N H T T S V S F T P S L D L A R Y L P K S S S G T 40989 atggacatctgtattcgaacctataacggaactacgcaaattggtagtgacgtctattcaaacggatggaggttcaacatcccc 197 M D I C I R T Y N G T T Q I G S D V Y S N G W R F N I P 41073 gattcagtacgtcctactttttcgggcatttctttagtagacacgacttcagcggttcgacagattttaacagggaacaacttc 225 D S V R P T F S G I S L V D T T S A V R Q I L T G N N F 41157 ctccaaatcatgtcgaacattcaagtcaacttcaacaatgcttccggcgcttacggatccactatccaagcatttcacgctgag 253 L Q I M S N I Q V N F N N A S G A Y G S T I Q A F H A E 41241 ctcgtaggtaaaaaccaagctatcaacgaaaacggcggcaaattgggtatgatgaactttaatggctccgctaccgtaagagca 281 L V G K N Q A I N E N G G K L G M M N F N G S A T V R A 41325 tgggttacagacacgcgaggaaaacaatcgaacgtccaagacgtatctatcaatgttatagaatactatggaccgtctatcaat 309 W V T D T R G K Q S N V Q D V S I N V I E Y Y G P S I N 41409 ttctccgttcaacgtactcgtcaaaatcctgcaattatccaagctcttcgaaatgctaaggtcgcacctataacggtaggaggt 337 F S V Q R T R Q N P A I I Q A L R N A K V A P I T V G G 41493 caacagaaaaacatcatgcaaattaccttctccgtggcgccgttgaacactactaatttcacagaagatagaggttcggcgtca 365 Q Q K N I M Q I T F S V A P L N T T N F T E D R G S'A S 41577 gggacgttcactactatttccctaatgactaactcgtccgcgaacttagctggtaactacgggccggacaagtcttacatagtt 393 G T F T T I S L M T N S S A N L A G N Y G P D K S Y I V 41661 aaggctaaaatccaagacaggttcacttcgactgaatttagtgctacggtagctaccgaatcagtagttcttaactatgacaag 421 K A K I Q D R F T S T E F S A T V A T E S V V L N Y D K 41745 gacggtcgacttggagttggtaaggttgtagaacaagggaaggcagggtcaattgatgcagcaggtgatatatatgctggaggt 449 D G R L G V G K V V E Q G K A G S I D A A G D I Y A G G 41829 cgacaagttcaacagtttcagctcactgataataatggagcattgaacaggggtcaatataacgatgtttggaataagcgtgaa 477 R Q V Q Q F Q L T D N N G A L N R G Q Y N D V W N K R E 41913 acagagtttacatggcgaagtaacaaatacgaggacaaccctacgggaactcgaggtgaatggggactatttcaaaatttctgg 505 T E F T W R S N K Y E D N P T G T R G E W G L F Q N F W 41997 ttagatagctggaaaatggttcaatccttcattacaatgtcaggaagaatgttcatcaggacagcgaacgatggaaacagctgg 533 L D S W K M V Q S F I T M S G R M F I R T A N D G N S W 42081 agacctaacaagtggaaagaggttctatttaagcaagacttcgaacagaataattggcagaaacttgttcttcaaagtgggtgg 561 R P N K W K E V L F K Q D F E Q N N W Q K L V L Q S G W 42165 aaccatcactcaacctatggcgacgcattctattcgaaaactcttgacggcatagtatatttgagaggaaatgtgcataaagga 589 N H H S T Y G D A F Y S K T L D G I V Y L R G N V H K G 42249 cttatcgacaaagaggctactattgcagtacttcctgaaggatttagaccgaaagtttcaatgtatcttcaggctctcaataac 617 L I D K E A T I A V L P E G F R P K V S M Y L Q A L N N 42333 tcatatggaaatgccattctatgtatatacactgacggaagacttgtggtgaaatcgaatgtagataattcttggttaaattta 645 S Y G N A I L C I Y T D G R L V V K S N V D N S W L N L 42417 gacaatgtctcatttcgtatttaa 42440 673 D N V S F R I dplORFOO5 23674 atggctaaaaaatcaaaagctatctcacacacagacgaactgattagtcagtcgtttgacagccccttggcaaagaatcaaaag 1 M A K K S K A I S H T D E L I S Q S F D S P L A K N Q K 23758 ttcaagaaagagcttcaggaagttgaaaagtattatcaatacttcgacggatttgatgtcacggacttgaatactgactatggg 29 F K K E L Q E V E K Y Y Q Y F D G F D V T D L N T D Y G 23842 caaacatggaagattgacgaagactcagtcgactataaacctactcgagaaattcgaaactatattcgacaacttatcaaaaag 57 Q T W K I D E D S V D Y K P T R E I R N Y I R-Q L I-K K 23926 caatcacgctttatgatgggtaaagagccagagcttatctttagtccagttcaagacaatcaagatgaacaggctgagaacaag 85 Q S R F M M G K E P E L I F S P V Q D N Q D E Q A E N K 24010 cgtattctattcgactctattttaaggaattgtaaattctggagcaaaagtacaaatgcattagtcgacgccacagtaggtaag 113 R I L F D S I L R N C K F W S K S T N A L V D A T V G K 24094 cgggtattgatgacagtagtagcaaatgccgctcaacaaattgacgtccagttttattcaatgcctcagttcacctatacagtt 141 R V L M T V V A N A A Q Q I D V Q F Y S M P Q F T Y T V 24178 gaccctagaaacccttccagcttgctttctgttgacattgtttatcaggacgagcgtacaaaaggaatgagcactgaaaaacaa WO 00/32825 PCT/IB99/02040 367 169 D P R N P S S L L S V D I V Y Q D E R T K G M S T E K Q 24262 ctttggcatcattatagatatgaaatgaaagctggaacaagtcaatcaggaattgcaacagctttagaagacattgaagaacaa 197 L W H H Y R Y E M K A G T S Q S G I A T A L E D I E E Q 24346 tgttggctcacttatgccttaacggatggagagtcgaaccaaatctatatgacagaaagtggccaaactactatcaaggagaca 225 C W L T Y A L T D G E S N Q I Y M T E S G Q T T I K E T 24430 gaggctaaacttgtagaaattgaagacaacctaggaaacaagattgaagttcctttaaaagttcaagaatccgccccaaccggc 253 E A K L V E I E D N L G N K I E V P L K V Q E S A P T G 24514 ttgaagcaaattccttgtcgagttattcttaatgaaccattgactaatgacatatacgggacaagcgatgtcaaagaccttatc 281 L K Q I P C R V I L N E P L T N D I Y G T S D V K D L I 24598 acagtagcagataacttgaacaaaactattagtgacttacgagattcacttcgatttaaaatgttcgagcagcctgttatcatt 309 T V A D N L N K T I S D L R D S L R F K M F E Q P V I I 24682 gatggctcttctaagtcaattcaaggaatgaagattgcgccaaacgctttggtcgaccttaagagtgaccctacttcctcaatc 337 D G S S K S I Q G M K I A P N A L V D L K S D P T S S I 24766 ggcggtactggaggcaagcaagctcaagtcacttccatttcaggaaacttcaacttccttccagcggctgaatattatttagag 365 G G T G G K Q A Q V T S I S G N F N F L P A A E Y Y L E 24850 ggcgctaagaaagccatgtatgaactaatggaccagccaatgcctgaaaaggtacaggaggcgccatcaggaattgcaatgcag 393 G A K K A M Y E L M D Q P M P E K V Q E A P S G I A M Q 24934 ttcttattctacgacctaatttctcgatgtgacggaaaatggattgagtgggatgatgctattcaatggctcattcaaatgctg 421 F L F Y D L I S R C D G K W I E W D D A I Q W L I Q M L 25018 gaagaaattttagcaacagtgaatgttgacttgggaaatattcctcaagatattcaatcaagttatcaaacacttacgacaatg 449 E E I L A T V N V D L G N I P Q D I Q S S Y Q T L T T M 25102 actatcgaacaccactatccaattcctagcgatgaactttctgctaagcaacttgcgctcactgaagttcaaactaatgtacgc 477 T I E H H Y P I P S D E L S A K Q L A L T E V Q T N V R 25186 agccaccaatcttacattgaagaattcagtaagaaggaaaaggcggacaaggaatgggaacgcattttggaagaacttgctcag 505 S H Q S Y I E E F S K K E K A D K E W E R I L E E L A Q 25270 cttgacgaaatctcagctggagcattgcctgtattagcaaacgaattaaacgaacaagaggagcctcaagatgaaacgagtgaa 533 L D E I S A G A L P V L A N E L N E Q E E P Q D E T S E 25354 gaagacgaagttgatgacaaagaaaaagaacaaactgaacaaccaaccgaagaaggagtcgacccagacgttcaaggttaa 25434 561 E D E V D D K E K E Q T E Q P T E E G V D P D V Q G * dplORF006 45296 atgattgaaatcgttatagcacgttcgaaagctaggcgaggtcgaaccctatttattgaaacatgggcaagcactgatgaagat 1 M I E I V I A R S K A R R G R T L F I E T W A S T D E D 45380 gcagttaaaatggcagaaaagatttccagcttgcccaatgtagtcgagacgtcttctaataacttcgaactaccttataagtat 29 A V K M A E K I S S L P N V V E T S S N N F E L P Y K Y 45464 ttcaataatgttatagacgctctagatgaatgggagcttCacatcttcggcgaacttgataaagatgttcaagactacattgac 57 F N N V I D A L D E W E L H I F G E L D K D V Q D Y I D 45548 tctcgaaaccgaatagcttcttcaagcaatgagcagttttcgttcaagactactccattcgcgcaccaggttgaatgtttgaa 85 S R N R I A S S S N E Q F S F K T T P F A H Q V E C F E 45632 tacgcacaagagcatccatgtttccttttaggcgatgagcaaggtttagggaaaactaaacaggcaattgatattgcagttagc 113 Y A Q E H P C F L L G D E Q G L G K T K Q A I D I A V S 45716 aggaaggcaagtttcaaacattgtttaatcgtatgttgcatatcagggctcaaatggaattgggcaaaagaagtaggtattcat 141 R K A S F K H C L I V C C I S G L K W N W A K E V G I H 45800 tcaaatgagtcagctcatattttaggaagtcgagtcactaaagatgggaaattagtgattgacggagtttctaaacgggcagaa 169 S N E S A H I L G S R V T K D G K L V I D G V S K R A E 45884 gacttgcttggtggccacgacgaattcttccttatcactaacattgaaactcttcgcgatgctgtgttcattaaatacttaaat 197 D L L G G H D E F F L I T N I E T L R D A V F I K Y L N 45968 gaactgacaaaaagcggagaaattggaatggttattattgacgagattcacaagtgtaagaacccttcaagtaagcaaggggct 225 E L T K S G E I G M V I I D E I H K C K N P S S K Q G A 46052 tcaattcaaaagctccaaagttattacaagatgggacttacaggaactcctctaatgaataacccaatcgatgtattcaatgtt 253 S I Q K L Q S Y Y K M G L T G T P L M N N P I D V F N V 46136 atgaagtggctaggggcggaacatcatacactgactcagttcaaagagcgatactgtatcgtcgaccagttcaatcaaatcact 281 M K W L G A E H H T L T Q F K E R Y C I V D Q F N Q I T 46220 ggatatcgaaatctagctgaacttcgcgagcttgtcaacgactacatgcttagaagaacgaaggaagaagttttagacctgcct 309 G Y R N L A E L R E L V N D Y M L R R T K E E V L D L P 46304 gaaaagattcgagtcacagagtatgtcgacatgaactcgaaacagtcaaaaatctataaggaagttttgactaaacttgttcaa 337 E K I R V T E Y V D M N S K Q S K I Y K E V L T K L V Q 46388 gaaatagataaagtcaagctcatgcctaaccctctagccgaaacgattcgacttcgacaagcgactggaaatccttcgatttta 365 E I D K V K L M P N P L A E T I R L R Q A T G N P S I L 46472 actactcaagatgtcaagtcttgcaagttcgaaagatgtatcgaaattgtcgaggaatgtatccagcaaggaaagtcctgcgtg 393 T T Q D V K S C K F E R C I E I V E E C I Q Q G K S C V 46556 atatttagcaattgggaaaaggttattgaacctcttgctaagatactttcgaagacagtcaaatgcaacctggtaacaggagaa 421 I F S N W E K V I E P L A K I L S K T V K C N L V T G E 46640 accgcagataagttcaacgaaattgaagaatttatgaatcacagaaaggcttctgttattttaggaactataggtgcgctagga 449 T A D K F N E I E E F M N H R K A S V I L G T I G A L G 46724 acaggatttactttgacgaaagcggatacggttattttcttagatagtccgtggacacgcgcagaaaaggaccaagccgaagat 477 T G F T L T K A D T V I F L D S P W T R A E K D Q A E D 46808 aggtgtcatagaattggcgcaaaaagttctgtcactatctacacgcttgtcgccaaaggtactgttgacgaacgtatagaagac 505 R C H R I G A K S S V T I Y T L V A K G T V D ER I E D 46892 cttattgaacggaaaggagaattagcagattatatcgtagatggtaagcctatgaaatctaaaattggtaaccttttcgatatc 533 L I E R K G E L A D Y I V D G K P M K S K I G N L F D I 46976 ctgcttaaatag 46987 561 L L K * dplORFOO7 22230 atgacaataagcctgagaaataaactacctaagttcaacttcgtcccttttagtaagaaacaactccagctcctaacatggtgg WO 00/32825 PCT/IB99/02040 368 1 M T I S L R N K L P K F N F V P F S K K Q L Q L L T W W 22314 acaaagggctcaccttttcgaactttcgatatcgtcatagcagacggttccattcgttcaggaaaaacagtatcgatggctctt 29 T K G S P F R T F D I V I A D G S I R S G K T V S M A L 22398 tcattttccctttgggccatgacggaattcaacggacaaaactttgccatctgtggtaagacaattcactcagctcgacgaaat 57 S F S L W A M T E F N G Q N F A I C G K T I H S A R R N 22482 gttattcagcctctaaagcaaatgctcacaagtcgcgggtatgaaattcgagatgttcgaaatgaaaatctacttattattaga 85 V I Q P L K Q M L T S R G Y E I R D V R N E N L L I I R 22566 cactttagaaatggcgaagaaattgtcaactacttctatatatttggaggaaaagatgagtcgagtcaagaccttatacagggg 113 H F R N G E E I V N Y F Y I F G G K D E S S Q D L I Q G 22650 gtaacattagcaggtatcttCtgtgatgaggtggcactgatgcctgaatcgtttgtcaaccaagcgacagggcgctgttccgta 141 V T L A G I F C D E V A L M P E S F V N Q A T G R C S V 22734 acaggttcgaaaatgtggttctcttgtaacccggccaatcctaatcactacttcaagaagaactggattgacaaacaggtcgaa 169 T G S K M W F S C N P A N P N H Y F K K N W I D K Q V E 22818 aagcgtatcttatatcttcactttacaatggacgacaaccctagcttgacggatagcattaaaaggcgctatgagaaaatgtat 197 K R I L Y L H F T M D D N P S L T D S I K R R Y E K M Y 22902 gctggagtcttcaggaaaagatttattctcggcctttgggtaacagcagatggtctagtttattcaatgttcaatgaagagcag 225 A G V F R K R F I L G L W V T A D G L V Y S M F N E E Q 22986 catgtcaaaaagctcaatatagaattcgaccgtttattcgtagcaggcgactttggtatctataatgcaacaaccttcggcctt 253 H V K K L N I E F D R L F V A G D F G I Y N A T T F G L 23070 tatggattctcgaaacgtcataagcgctaccatctaattgagtcatactaccactcagggcgcgaggcggaagagcaactaact 281 Y G F S K R H K R Y H L I E S Y Y H S G R E A E E Q L T 23154 gaggcggatgttaattcgaatattcaatttagttcagttctacaaaagactactaaagagtacgcaaatgatttagtcgatatg 309 E A D V N S N I Q F S S V L Q K T T K E Y A N D L V D M 23238 atacgaggaaagcaaatcgaatatataattctcgacccgtctgcttctgctatgattgttgaacttcaaaagcatcttatata 337 I R G K Q I E Y I I L D P S A S A M I V E L Q K H P Y I 23322 gctagaaagaatatccctatcattcctgctcgaaatgacgtgacgcttggcatttcatttcacgctgaactcttggctgagaat 365 A R K N I P I I P A R N D V T L G I S F H A E L L A E N 23406 agatttacactcgaccctagcaacacgcacgacattgatgaatactatgcttacagctgggacagtaaagcgagccaaacggga 393 R F T L D P S N T H D I D E Y Y A Y S W D S K A S Q T G 23490 gaagatagagtcattaaagagcatgaccactgcatggataggaacagatatgcctgtctcactgacgctctaatcaacgatgac 421 E D R V I K E H D H C M D R N R Y A C L T D A L I N D D 23574 ttcggtttcgaaatacaaatattatccggaaaaggcgctagaaactaa 23621 449 F G F E I Q I L S G K G A R N * dplORFOO8 49624 gtgatacagcttcaagtcttaaataaagttctcgaagaaaagagcttatccattttagaaaataatggaattgaccaagaatac 1 V I Q L Q V L N K V L E E K S L S I L E N N G I D Q E Y 49708 ttcacggattatttagacgagtatcaatttattcaagaacacttttcgagatatggaagagttccggacgacgaaactattctc 29 F T D Y L D E Y Q F I Q E H F S R Y G R V P D D E T I L 49792 gaccattttcctggattcgaatttttcgaaattggcgaaactgatgaataccttatcgacaagctaaaagaggagcatctatat 57 D H F P G F E F F E I G E T D E Y L I D K L K E E H L Y 49876 aattcacttgttccaattttaacggaagcggctgaggacattcaagtagatagtaacattgcgattgcgaatataattccaaaa 85 N S L V P I L T E A A E D I Q V D S N I A I A N I I P K 49960 ctagaagaacttttcaatcgctctaaattcgtaggcggactagacattgctcgaaatgctaaacttcgactagactgggcgaat 113 L E E L F N R S K F V G G L D I A R N A K L R L D W A N 50044 actattagaaaccatgacggtgaaagacttggaatatcgacagggtttgaactattggacgacgtgcttggaggcttacttcct 141 T I R N H D G E R L G I S T G F E L L D D V L G G L L P 50128 ggtgaggatttgattgtcataatggctcgacctggacaaggtaagtcgtggactattgataaaatgcttgcaactgcttggaag 169 G E D L I V I M A R P G Q G K S W T I D K M L A T A W K 50212 aacgggcatgatgtccttctatatagcggggaaatgagtgaaatgcaagttggtgctcgtatagatactattctttcgaatgtt 197 N G H D V L L Y S G E M S E M Q V G A R I D T I L S N V 50296 agcatcaattcaattaccaaagggatttggaacgaccatcagttcgaaaaatatgaggaccatattcaagcaatgactgaggct 225 S I N S I T K G I W N D H Q F E K Y E D H I Q A M T E A 50380 gaaaattcccttgtggtagtcacgccctttatgattggaggaaagaaccttacccctgcaattttagatagcatgatatctaaa 253 E N S L V V V T P F M I G G K N L T P A I L D S M I S K 50464 tatagaccatctgtggtggggattgaccagctttcactcatgagcgagtcttatccaagcagggagcagaagcgaatccagtac 281 Y R P S V V G I D Q L S L M S E S Y P S R E Q K R I Q Y 50548 gccaacatcaccatggacctatataagatttctgctaaatatggaattcctattgtgcttaatgtccaagcagggcgttcggct 309 A N I T M D L Y K I S A K Y G I P I V L N V Q A G R S A 50632 aaaactgaaggcgctgaaagtatggaactagaacatatagcagaaagtgatggagtaggtcaaaatgctagcagagttatcgct 337 K T E G A E S M E L E H I A E S D G V G Q N A S R V I A 50716 atgaagcgtgacgaaaaatccggcatacttgaactatctgtcgttaaaaaccgatatggcgaagaccgaaaaatcatcgaatat 365 M K R D E K S G I L E L S V V K N R Y G E D R K I I E Y 50800 atgtgggacgttgaaactggaacctatactcttataggattcaaagaggaaggcgaagaaggaactgaaaaaggcgaaagctct 393 M W D V E T G T Y T L I G F K E E G E E G T E K G E S S 50884 ccattgaaagcaaaagcctctaggtcgactgctcgtcttcgaagtaaggttacaagggaaggagttgaagcattttga 50961 421 P L K A K A S R S T A R L R S K V T R E G V E A F * dplORFOO9 13160 atgacagactttaaaaaacgcttcaagaaagcagtaacagaaacaatcaatcgtgacggtatcgagaaccttatggattggtc 1 M T D F K K R F K K A V T E T I N R D G I E N-L M_D-W L 13244 gaaaatgataccaatttcttctcaagtccagcaagcactcgataccatggaagctatgaaggtggacttgtggagcactcatta 29 E N D T N F F S S P A S T R Y H G S Y E G G L V E H S L 13328 aacgtgttcaatcaactacttttcgaaatggataccatggtaggcaaaggctgggaagacatttacccaatggaaacagttgca 57 N V F N Q L L F E M D T M V G K G W E D I Y P M E T V A 13412 atcgtagcactatttcacgacctttgcaaagttggtcagtatcgtgaaactgaaaaatggcgcaagaacagcgacggtgaatgg 85 I V A L F H D L C K V G Q Y R E T E K W R K N S D G E W 13496 gaaagctatttagcatatgaatacgaccctgagcaacttacaatgggacatggtgcaaaatctaatttccttcttcaacgtttc WO 00/32825 PCT/IB99/02040 369 113 E S Y L A Y E Y D P E Q L T M G H G A K S N F L L Q R F 13580 attcaactcacgccagttgaagctcaagcaattttctggcatatgggagcctatgatattagtccttatgcaaatttgaatgga 141 I Q L T P V E A Q A I F W H M G A Y D I S P Y A N L N G 13664 tgtggagcagccttcgaaactaatccacttgcattcttaatccatcgcgcagatatggccgcaacttatgtagtcgaaaatgaa 169 C G A A F E T N P L A F L I H R A D M A A T Y V V E N E 13748 aacttcgaatactctcaaggtccagttgaacaagaggctgaggttgaagaagtagttgaagaaaaacctaagagttcaactcgt 197 N F E Y S Q G P V E Q E A E V E E V V E E K P K S S T R 13832 aagaaacctgcgcctaaggaagaaaaagttgaagaggctgaagaaaaaccaaaagctggaatcactcgacgtcgcaaacctgcg 225 K K P A P K E E K V E E A E E K P K A G I T R R R K P A 13916 ccaaaagaggaagaggtagaagagcctaaagaagagcctaagaaagcatcttctaaaattcgaatgcctaaaaagactgaaaag 253 P K E E E V E E P K E E P K K A S S K I R M P K K T E K 14000 gtcgaagaggtagaaagcgcagacgagccgaaagttgaagaagcagaggacgacaatgtggtggtacctgctggatatgttcga 281 V E E V E S A D E P K V E E A E D D N V V V P A G Y V R 14084 gatgtctactacttctacagtgaagtcgctgacgtttactacaagaaagatgtcgacgagcctgacgatgacagcgacattctt 309 D V Y Y F Y S E V A D V Y Y K K D V D E P D D D S D I L 14168 gtagacgaagaagagtacatggacgcaatgtgtcctgtattagaagaagacttcttctacgaacttgacggcaaggttcacaaa 337 V D E E E Y M D A M C P V L E E D F F Y E L D G K V H K 14252 ttagcaaaaggtgaacgcttgccggaagaatacgacgaagaaacttgggaacctatcactgaagcagaatacatcaagcgaaca 365 L A K G E R L P E E Y D E E T W E P I T E A E Y I K R T 14336 gaaaaacctaaagcagttgcaaaacctactcgaaaaactccagcgccttctcgtcgccctcgcccttaa 14404 393 E K P K A V A K P T R K T P A P S R R P R P * dplORFOO 8699 atgaaattggaacagttgatgaaggactggaataaggattcgaaagctcttgtagcagttcaaggacttgaacgtgaagcgctt 1 M K L E Q L M K DOWN K D S K A L V A V Q GCL E R E A L 8783 ccaagaatccctttttctgcgccttctatgaattatcaaacctacggcgggctccctcgaaaaagggtagttgaattcttcggt 29 P R I P F S A P S M N Y Q T Y G G L P R K R V V E F F G 8867 cctgagtcaagtgggaaaactacttcagctctcgacattgtcaagaatgcgcaaatggtatttgagcaggaatgggaacagaag 57 P E S S G K T T S A L D I V K N A Q M V F K Q E W K Q K 8951 actgaagaactcaaggaaaagctggaaaatgcgcgtgcatccaaagctagcaagactgctgtcaaggaacttgaaatgcaactc 85 T K E L K E K L E N A K A S K A S K T A V K E L E M Q L 9035 gatagtcttcaagagcctcttaagattgtatatcttgaccttgagaatacattagacactgagtgggctaaaaagattggagtc 113 D S L Q E P L K I V Y L D L K N T L D T K W A K K I G V 9119 gatgttgacaatatttggatagttcgccctgaaatgaacagcgctgaagaaatacttcaatatgttttagacattttcgaaaca 141 D V D N I W I V R P K M N S A K K I L Q Y V L D I F E T 9203 ggtgaagttggcctagtagttctagattccttgccttacatggtcagtcaaaaccttattgatgaagagttgactaaaaaggcc 169 G K V G L V V L D S L P V M V S Q N L I D K E L T K K A 9287 tatgcaggaatctcagcgcctttgactgaatttagtcgaaaggttactcctcttcttactcgctacaatgcaatattcctaggc 197 V A C I S A P L T E F S R K V T P L L T R V N A I F L G 9371 atcaatcaaattcgagaagatatgaatagtcagtacaatgcctattcaactccaggcggaaagatgtggaagcatgcttgtgca 225 1 N Q I R E 0 M N S Q Y N A Y S T P G G K M W K H A C A 9455 gttcgacttaaatttagaaaaggtgactaccttgacgaaaacggtgcatcattgacccgtactgctcgaaaccctgcagggaat 253 V K L K F K K G D V L D K N G A S L T R T A R N P A G N 9539 gtagtagagtcattcgtcgagaagaccaaagcatttaagccggacagaaaattagtttcctatacgctttcctatcatgatgga 281 V V K S F V E K T K A F K P D R K L V S Y T L S V H D G 9623 attcaaattgaaaatgaccttgtagatgtcgctgtcgaatttggagtcattcaaaaggcaggggcatggttcagtatcgtcgac 309 1 Q I K N D L V D V A V K F G V I Q K A G A W F S I V D 9707 ct tgaaact ggagaaat tat ga cagat gaagacgaagaac cat tgaagt t ccaaggc aaggc aaat ct agt tcgacgc t tcaag 337 L K T C K I M T D K D K K P L K F Q C K A N L V R K F K 9791 gaggatgactacttattcgacatggtgatgactgcggttcacgaaattatcactcgagaagaaggctaa 9859 365 K D D V L F D M V M T A V H K I I T R K E CG dplORFOll 28017 atgaatatttatgattatatcaacgcaggggagattgctagctacattcaagcacttccttcaaacgctcttcaataccttgga 1 M N I V D Y I N A C K I A S V I Q A LP S N A L Q V L C 28101 ccaactcttttccctaatgctcaacaaacagggacagacatttcatggctcaagggtgcaaataatttgccagtaactatccag 29 P T L F P N A Q Q T C T D I S W L K C A N N L P V T I Q 28185 ccatctaactacgacgcgaaagcaagtcttcgtgaacgtgctggatttagcaaacaagctactgagatggcattcttccgtgag 57 P S N V 0 A K A S L R K R A C F S K Q A T E M A F F R E 28269 tctatgcgacttggtgaaaaagaccgtcaaaacttgcaaatgctattgaaccaaagttcagctcttgcccaaccacttatcact 85 S M R L C K K D R Q N L Q M L L N Q S S A L A Q P L I T 28353 caactctataatgatactaagaaccttgtagacggtgttgaagcgcaagcagaatacatgcgtatgcaattgcttcaatacggt 113 Q L V N D T K N L V D C V E A Q A K V M R M Q L L Q V C 28437 aaattcactgtcaaatcaactaacagcgaggctcaatacacttacgactacaacatggatgctaagcaacaatatgcagtcact 141 K F T V K S T N S K A Q V T V D Y N M D A K Q Q V A V T 28521 aagaaatggactaacccagctgaaagtgaccctatcgctgacattttagcagcaatggatgacatcgaaaatcgtacaggtgtt 169 K K W T N P A E S D P I A D I L A A M D D I K N R T C V 28605 cgccctactcgaatggtcttgaaccgaaacacttataaccaaatgactaagagtgactctatcaagaaagctcttgcaattggt 197 K P T K M V L N R N T V N Q M T K S D S I K K A L A I C 28689 gt tcaaggt tct tgggaaaact t c ttgct tct tgcaagtgacgctgagaaatt cat cgc tgaaaaaac aggt ct tcaa-t c~c 225 V Q C S W E N F L L LA S D A K K F I A E K T G JL Q I A 28773 gtctactctaagaaaattgctcagttcgctgacgctgacaaacttcctgacgttggtaacattcgtcagttcaacttgattgac 253 V V S K K I A Q F A D A D K L P D V C N I R Q F N L I D 28857 gacggtaaagtggtattgcttccacctgacgcagttggtcacacttggtacggtactactccagaagcattcgacttggcttca 281 D C K V V L L P P D A V C H T W Y C T T P E A F D L A S 28941 ggcggaacagacgct caagt tcaagtt ct t tcaggcggac c taccgt tacaact tatc t tgaaaaacat cctgt caacat tgca 309 C C T D A Q V Q V L S C C P T V T T V L E K H P V N I A WO 00/32825 PCT/IB99/02040 370 29025 acagttgtatcagctgttatgattccatcattcgaaggaattgactatgtaggagttctcacaactaattag 29096 337 T V V S A V M I P S F E G I D Y V G V L T T N * dplORF012 5346 atgagtattaagttcaaaaccgaagaactttcaaaaattgtttctcagctcaataagttgaagcctagcaagttgctagaaatc 1 M S I K F K T E E L S K I V S Q L N K L K P S K L L E I 5430 acaaactattggcatatttttggtgacggcgaatgcgtcatgtttacagcgtatgatggctcaaacttccttcgatgcattatc 29 T N Y W H I F G D G E C V M F T A Y D G S N F L R C I I 5514 gacagcgatgttgaaattgacgtgattgtgaaagcagagcagtttggaaaacttgtagaaaagaccacggccgcaaccgtcaca 57 D S D V E I D V I V K A E Q F G K L V E K T T A A T V T 5598 ttagttcctgaagaatcttcgctaaaagttattgggaatggtgagtacaatattgatattgttacagaagatgaagagtaccct 85 L V P E E S S L K V I G N G E Y N I D I V T E D E E Y P 5682 acattcgaccacttgctcgaagacgtgagtgaagaaaatgctctcactttgaaaagctcgctgttctacggaatcgccaatatc 113 T F D H L L E D V S E E N A L T L K S S L F Y G I A N I 5766 aacgattctgcggtatctaaatcaggagcagatggaatttataccggcttcctgttaaaaggcggaaaagcaattactacagac 141 N D S A V S K S G A D G I Y T G F L L K G G K A I T T D 5850 atcattcgcgtatgtatcaaccctatcaaggaaaagggactagaaatgctcattccttacaacctaatgagtattttagcaagt 169 I I R V C I N P I K E K G L E M L I P Y N L M S I L A S 5934 attcctgatgagaagatgtacttctggcaaattgacgatactactgtctatatttcatcggcttcagtcgaaatttatggaaaa 197 I P D E K M Y F W Q I D D T T V Y I S S A S V E I Y G K 6018 ttgatggaaggtatggaagattatgaagacgtttcacagcttgactcaattgagtttgaagatgatgcggctatccctacagca 225 L M E G M E D Y E D V S Q L D S I E F E D D A A I P T A 6102 gaaatcctgagcgtattagaccgccttgtactattcacttcagcctttgacaaaggaaccgtcgaattcttattcttgaaagac 253 E I L S V L D R L V L F T S A F D K G T V E F L F L K D 6186 cgacttcgaattaaaacttctactagcagttatgaagacatcatgtacgcatctgctggcaagaaagtttcgaagaaagaattc 281 R L R I K T S T S S Y E D I M Y A S A G K K V S K K E F 6270 acttgccaccttaacagcttactcttgaaggaaattgtatcaaccgtcaccgaagaaaacttcactgtctcttatggaagcgaa 309 T C H L N S L L L K E I V S T V T E E N F T V S Y G S E 6354 accgcaattaagatttcatcgaatggtgtcgtttacttcctagcacttcaagagccggaagaataa 6419 337 T A I K I S S N G V V Y F L A L Q E P E E * dplORF013 10215 atgaatttagcttctaaataccgtcctcaaactttcgaggaagtggtagctcaagaatatgtcaaagaaattcttttgaatcaa 1 M N L A S K Y R P Q T F E E V V A Q E Y V K E I L L N Q 10299 ttacaaaatggcgctatcaaacacggctatctattctgtggtggcgctggaactggtaaaaccactactgctcgaattttcgcg 29 L Q N G A I K H G Y L F C G G A G T G K T T T A R I F A 10383 aaggatgtgaacaaaggacttggctctcctattgaaattgatgctgcttctaataatggggtagaaaatgttcgaaacattatt 57 K D V N K G L G S P I E I D A A S N N G V E N V R N I I 10467 gaagattctagatacaagtctatggacagcgagttcaaagtttacatcattgacgaggttcatatgctttcaaccggagcattt 85 E D S R Y K S M D S E F K V Y I I D E V H M L S T G A F 10551 aatgcgctgttgaaaacattagaagagccctcatcgggaaccgtgttcattctatgtactactgaccctcaaaagattcctgac 113 N A L L K T L E E P S S G T V F I L C T T D P Q K I P D 10635 actattctcagtcgagttcaacggtttgactttactcgaattgataatgacgacatcgttaatcaacttcaatttattatcgaa 141 T I L S R V Q R F D F T R I D N D D I V N Q L Q F I I E 10719 agtgaaaatgaagaaggagctggttatagttatgagcgtgacgccctttcgtttattgggaaacttgcaaatggaggaatgcgt 169 S E N E E G A G Y S Y E R D A L S F I G K L A N G G M R 10803 gacagtatcacaaggctcgaaaaagtccttgattatagtcatcacgttgacatggaagccgtttctaatgcactaggagttccg 197 D S I T R L E K V L D Y S H H V D M E A V S N A L G V P 10887 gactacgaaacattcgcttcacttgttgaagctattgccaactatgacggctcaaagtgtttagaaattgtaaatgacttccac 225 D Y E T F A S L V E A I A N Y D G S K C L E I V N D F H 10971 tactcaggaaaagacttgaaattagtgactcgaaactttacagacttccttttagaggtttgtaagtattggctagttcgagat 253 Y S G K D L K L V T R N F T D F L L E V C K Y W L V R D 11055 atttcaatcactcaacttcctgctcattttgaaagtaagctagagcaattctgtgaggcttttcaatatcctactctattgtgg 281 I S I T Q L P A H F E S K L E Q F C E A F Q Y P T L L W 11139 atgctagaagaaatgaatgaacttgctggagttgttaaatgggagcctaatgctaaaccgataattgaaaccaaacttcttttg 309 M L E E M N E L A G V V K W E P N A K P I I E T K L L L 11223 atgagcaaggaggagtga 11240 337 M S K E E * dplORF014 50961 atgaaagtaaatggtcttcaaattgaagcgactcctgaacaaataattgaaaaactttcgagacaacttgaagacgaaggaaca 1 M K V N G L Q I E A T P E Q I I E K L S R Q L E D E G T 51045 ttcatttttagacgaactaagtcgcttggaagcaactatcaattctcatgcccgtttcatgcaggagggactgaaaagcatccc 29 F I F R R T K S L G S N Y Q F S C P F H A G G T E K H P 51129 tcttgtggcatgagtagaaatccttcttattcaggaagtaaggtgacggaagctggaacggttcactgtttcacttgcggctac 57 S C G M S R N P S Y S G S K V T E A G T V H C F T C G Y 51213 acttcaggactaactgaattcgtctcgaatgtattaggtcgaaacgatggagggttctatggaaaccagtggctgaaaaggaat 85 T S G L T E F V S N V L G R N D G G F Y G N Q W L K R N 51297 tttggaacatctagcgaagtagttaggcaaggcgtcagccctgaagcgtttcgaagaaatgggagaactgaaaaagtcgagcat 113 F G T S S E V V R Q G V S P E A F R R N G R T E K V E H 51381 aaaatcattcctgaagaggaacttgataaataccggtttattcatccttatatgtatgaacggaaattgacggacgagctcatc 141 K I I P E E E L D K Y R F I H P Y M Y E R K L-T D E--io I 51465 gagatgtttgatgtaggttatgacaaactgcatgattgcatcacctttccagtacggaacctcaagggcgaacagtattcttc 169 E M F D V G Y D K L H D C I T F P V R N L K G E T V F F 51549 aaccgtcgaagtgttcgttctaagtttcaccagtacggtgaagatgaccctaaaacggaatttctttatggccaatatgagctt 197 N R R S V R S K F H Q Y G E D D P K T E F L Y G Q Y E L 51633 gtagcatttcgagactattttgaaaaacctattagtcaagtattcgtgactgagtctgttatcaactgttgacttttggtca 225 V A F R D Y F E K P I S Q V F V T E S V I N C L T L W S 51717 atgaagattccagcagtcgctcttatgggagtaggtggaggaaatcaaatcaatttactaaaacgacttcttatagaaatatt WO 00/32825 PCT/IB99/02040 371 253 M K I P A V A L M G V G G G N Q I N L L K R L P Y R N I 51801 gttctagcacttgaccctgataacgctgggcagacagcgcaggaaaaactctaccgacagttaaagcgaagcaaggtcgttaga 281 V L A L D P D N A G Q T A Q E K L Y R Q L K R S K V V R 51885 tttttgaactaccctaaagagttctatgataataagtgggatataaacgaccatccggaattattaaattttaatgatttagtc 309 F L N Y P K E F Y D N K W D I N D H P E L L N F N D L V 51969 ttgtag 51974 337 L * dplORF015 3793 atgggatttaatctatacttcgcaggaggtcacgctattagcactgacgattatttgaaggaaagaggagccaatcgcctattc 1 M G F N L Y F A G G H A I S T D D Y L K E R G A N R L F 3877 aatcaactgtacgaaagaaacgggattggcaaaaggtggattgagcataagaaaaccaatccaagcactacttcaaaactattc 29 N Q L Y E R N G I G K R W I E H K K T N P S T T S K L F 3961 gtcgactctagtgcatattctgctcataccaaaggggctgaagttgacattgacgcctatatcgaatacgtgaatgataacgtg 57 V D S S A Y S A H T K G A E V D I D A Y I E Y V N D N V 4045 ggaatgtttgactgtatcgccgaactcgataaaattcctggtgtatttagacagcctaagacacgtgaacagcttttggaagca 85 G M F D C I A E L D K I P G V F R Q P K T R E Q L L E A 4129 ccacaaatttcttgggataattatctatacatgcgcgagcgaatggttgagaaagacaagctcttacctattttccatatggga 113 P Q I S W D N Y L Y M R E R M V E K D K L L P I F H M G 4213 gaagactttaaatggctcaacttgatgctcgaaactacattcgaaggcggaaagcatattccttacattggaatttcaccagcc 141 E D F K W L N L M L E T T F E G G K H I P Y I G I S P A 4297 aatgactcgactacgaagcataaagacaagtggatggaaagagtattcgaagttattcgaaacagttctaatccagacgttaag 169 N D S T T K H K D K W M E R V F E V I R N S S N P D V K 4381 actcacgcatttgggatgacagttactagccaattagagcgtcacccattctatagcgccgactctacttctgtactgctcaca 197 T H A F G M T V T S Q L E R H P F Y S A D S T S V L L T 4465 ggagcgatgggaaacattatgacgtcaaaaggattagttgacttgtcacagaagaatggaggaattgatgctgtccgtaggctg 225 G A M G N I M T S K G L V D L S Q K N G G I D A V R R L 4549 ccaaaaccggttcaagttgaaattgaatccattatcgaagaaactggagcgcattttagcctagagcaattagttgaggactat 253 P K P V Q V E I E S I I E E T G A H F S L E Q L V E D Y 4633 aaacttcgagcattgttcaatgttcaatacatgctgaattgggcagagaactatgaattcaagggaattaaaaatgtcaacgt 281 K L R A L F N V Q Y M L N W A E N Y E F K G I K N R Q R 4717 cgactattttag 4728 309 R L F * dplORF016 43413 atgggagtcgatattgaaaaaggcgttgcgtggatgcaggcccgaaagggtcgagtatcttatagcatggactttcgagacggt 1 M G V D I E K G V A W M Q A R K G R V S Y S M D F R D G 43497 cctgatagctatgactgctcaagttctatgtactatgctctccgctcagccggagcttcaagtgctggatgggcagtcaatact 29 P D S Y D C S S S M Y Y A L R S A G A S S A G W A V N T 43581 gagtacatgcacgcatggcttattgaaaacggttatgaactaattagtgaaaatgctccgtgggatgctaaacgaggcgacatc 57 E Y M H A W L I E N G Y E L I S E N A P W D A K R G D I 43665 ttcatctggggacgcaaaggtgctagcgcaggcgctggaggtcatacagggatgttcattgacagtgataacatcattcactgc 85 F I W G R K G A S A G A G G H T G M F I D S D N I I H C 43749 aactacgcctacgacggaatttccgtcaacgaccacgatgagcgttggtactatgcaggtcaaccttactactacgtctatcgc 113 N Y A Y D G I S V N D H D E R W Y Y A G Q P Y Y Y V Y R 43833 ttgactaacgcaaatgctcaaccggctgagaagaaacttggctggcagaaagatgctactggtttctggtacgctcgagcaaac 141 L T N A N A Q P A E K K L G W Q K D A T G F W Y A R A N 43917 ggaacttatccaaaagatgagttcgagtatatcgaagaaaacaagtcttggttctactttgacgaccaaggctacatgctgct 169 G T Y P K D E F E Y I E E N K S W F Y F D D Q G Y M L A 44001 gagaaatggttgaaacatactgatggaaattggtattggttcgaccgtgacggatacatggctacgtcatggaaacggattggc 197 E K W L K H T D G N W Y W F D R D G Y M A T S W K R I G 44085 gagtcatggtactacttcaatcgcgatggttcaatggtaaccggttggattaagtattacgataattggtattattgtgatgct 225 E S W Y Y F N R D G S M V T G W I K Y Y D N W Y Y C D A 44169 accaacggcgacatgaaatcgaatgcgtttatccgttataacgacggctggtatctactattaccggacggacgtctggcagat 253 T N G D M K S N A F I R Y N D G W Y L L L P D G R L A D 44253 aaacctcaattcaccgtagagccggacgggctcattactgctaaagtttaa 44303 281 K P Q F T V E P D G L I T A K V * dplORF017 11242 atgattggacagggacttgttaaatctaccatttcgaaatggaaacaacttccaaaatatataatcgtcgaaggtgaagtaggt 1 M I G Q G L V K S T I S K W K Q L P K Y I I V E G E V G 11326 tcaggacggaagaccttaatccgttatattgcttcgaaatttgacgctgattctattgtagtaggaacgagtgtagatgacatt 29 S G R K T L I R Y I A S K F D A D S I V V G T S V D D I 11410 cgaaacatcattcaggatgcacagactattttcaaggcgagaatctacgtgatagacggaaatagcctgtcaatgtcagctctt 57 R N I I Q D A Q T I F K A R I Y V I D G N S L S M S A L 11494 aactcgcttttgaagatagcggaagagccacctttaaactgtcatatagccatgactgttgatagcatcaataatgctttacct 85 N S L L K I A E E P P L N C H I A M T V D S I N N A L P 11578 acgcttgcaagtagagcaaaagttctaaccatgctaccttatactaatgaagagaaaatgcagtttgtcaagtcctacaagaag 113 T L A S R A K V L T M L P Y T N E E K M Q F V K S Y K K 11662 gtagatacttcaggaattgacgaccgagcgattgtagactattgcaatcttgccagcaatcttcaaatgcttgaagacatatta 141 V D T S G I D D R A I V D Y C N L A S N L Q M-L E D-I L 11746 gaatatggcgcagaagagctatttgaaaaggttacaacattttatgacttaatatgggaggcaagtgtagcaatcgctaaag 169 E Y G A E E L F E K V T T F Y D L I W E A S A S N S L K 11830 gttactaattggctcaaatttaaggaaactgatgaaggaaaaattgagcctaaacttttcctcaactgtcttttaaattggtcg 197 V T N W L K F K E T D E G K I E P K L F L N C L L N W S 11914 acagttgtcatcaggaagcactatgtagaaatgtctttcgaagaacttgaggcccatgaccttttagtgagggaagcatctagg 225 T V V I R K H Y V E M S F E E L E A H D L L V R E A S R WO 00/32825 PCT/IB99/02040 11998 tgtttgcgaaaggtatctaaaaagggctcaaatgcgcgtgtctgcgtgaacgaatttatcaggagggtcaaacaagttgagtga 12081 253 C L R K V S K K G S N A R V C V N E F I R R V K Q V E * dplORF018 35847 atggctagcagacagacgctattggtcgacggaattgaccttgtcgacaaaggtgcaaccgtgctagaatatgtaggactcact 1 M A S R Q T L L V D G I D L V D K G A T V L E Y V G L T 35931 ttcgcaggatttaaggactcaggatttaaaaaccctgaaggcatagacggagtattagattctccgtctaatgctatgtccgct 29 F A G F K D S G F K N P E G I D G V L D S P S N A M S A 36015 cttactggaagcgtgaccttaatgttccacggagaaaccgaaaagcaagttaatcaaaaatacaggcagttcaaacaatttatt 57 L T G S V T L M F H G E T E K Q V N Q K Y R Q F K Q F I 36099 cgctcgaagtcattttggagaatttcgacacttgaagaccctggatactatcgaacgggaaaatttttaggagaaaccgagcaa 85 R S K S F W R I S T L E D P G Y Y R T G K F L G E T E Q 36183 ggaaaacttgtagacgttcaagcctttaaagatacttcccttgtagttaaattagggattcagttcaaagatgcttacgagtac 113 G K L V D V Q A F K D T S L V V K L G I Q F K D A Y E Y 36267 agcgactcaactgttcgaaaggtttataagtttcaacccgctttgggaggcgatagcttacctaacccaggaagacctactcga 141 S D S T V R K V Y K F Q P A L G G D S L P N P G R P T R 36351 caatttagagtagaaataagaactacttctcaaatcaaaggatattttcgaattggcgaaaaaagttcaggacagtttgttgag 169 Q F R V E I R T T S Q I K G Y F R I G E K S S G Q F V E 36435 ttcggtactaattcagtattgatggaaagtggctcgattattattctaaatcttggaacttttgaacttattaaaattagcagt 197 F G T N S V L M E S G S I I I L N L G T F E L I K I S S 36519 gcaaatcaagcgactaacttatttagatacattaaacgaggcgcattcttcaagattcctaatggaaattcaacaattaccatt 225 A N Q A T N L F R Y I K R G A F F K I P N G N S T I T I 36603 gaataccgagccgatgacgcagcagcttggacctctactcttcccgctcaagttgaactgtttctaaatccgtcttactattag 36686 253 E Y R A D D A A A W T S T L P A Q V E L F L N P S Y Y * dplORF019 12161 atgaatgtttatctcaatcaaatgggaaatgtagttcgagaaacttcggtttcaacagtctggaaaaccctcactcaaaaaggg 1 M N V Y L N Q M G N V V R E T S V S T V W K T L T Q K G 12245 ctcgtttctaatcatcgaatattcgctgttcgagatgataaggagtttctgtctaatgagtcgaggtggaaaaggcttccggat 29 L V S N H R I F A V R D D K E F L S N E S R W K R L P D 12329 gttagatatgggacacttgttttgatggttactaaaattgacaagcgaagcaagttgctaaaggcctttcctgataattgtgtt 57 V R Y G T L V L M V T K I D K R S K L L K A F P D N C V 12413 gagtttgagaaaatgactgacgcgcagttgaaaaggcattttgtgtctaaatactcgactattgatagcgacatgattgacatg 85 E F E K M T D A Q L K R H F V S K Y S T I D S D M I D M 12497 gttatccagttctgtctaaacgattactctagaattgacaatgaattggacaagctgtcgcgattgaaaaaggttgacgcatca 113 V I Q F C L N D Y S R I D N E L D K L S R L K K V D A S 12581 gtagttgaatccattgtcaagcacaagaccgaaattgacattttcagcctagttgatgatgtattggaatataggccggagcag 141 V V E S I V K H K T E I D I F S L V D D V L E Y R P E Q 12665 gcaattatgaaagtgactgaacttttagccaaaggagaaagtcctattggattgcttaccttgctttatcaaaattttaataac 169 A I M K V T E L L A K G E S P I G L L T L L Y Q N F N N 12749 gcttgtcttgtgctaggagccgatgagcctaaagaagccaatctaggcattaagcagttcttaatcaataagattgtctataac 197 A C L V L G A D E P K E A N L G I K Q F L I N K I V Y N 12833 tttcaatacgagctggactcagcctttgaaggcatggctattttaggtcaagctatcgagggcataaagaatggtcgctataca 225 F Q Y E L D S A F E G M A I L G Q A I E G I K N G R Y T 12917 gaaagttcagtggtctatatttctttgtataaaattttttcacttacttaa 12967 253 E S S V V Y I S L Y K I F S L T * dplORF020 1864 atggttaatcaatacaatcagcctgaaagaggcaagattcgaatcaatgttcgcgaccctgagaaaatgcctatcatggaaatt 1 M V N Q Y N Q P E R G K I R I N V R D P E K M P I M E I 1948 ttcggtcctacaattcaaggtgaaggaatggttataggtcaaaagactattttcattcgaactggtggatgcgactatcattgc 29 F G P T I Q G E G M V I G Q K T I F I R T G G C D Y H C 2032 aactggtgtgactcagcctttacctggaacggtactactgagccggaatatatcacaggcaaagaagctgctagtcgaatcttg 57 N W C D S A F T W N G T T E P E Y I T G K E A A S R I L 2116 aaactagctttcaatgataaaggtgaacagatttgtaaccacgtgacattgactggaggaaatcctgccttaatcaacgagcct 85 K L A F N D K G E Q I C N H V T L T G G N P A L I N E P 2200 atggctaagatgatttcgattctaaaagaacatggattcaagtttggtctcgaaactcaaggaactcgattccaagaatggttc 113 M A K M I S I L K E H G F K F G L E T Q G T R F Q E W F 2284 aaagaagtaagcgatatcactattagtcctaaaccgccttcaagtggaatgagaactaatatgaaaattcttgaagctattgta 141 K E V S D I T I S P K P P S S G M R T N M K I L E A I V 2368 gatagaatgaatgatgaaaaccttgactggtcatttaaaatcgttatctttgacgaaaatgacctagcttatgcgcgtgatatg 169 D R M N D E N L D W S F K I V I F D E N D L A Y A R D M 2452 tttaaaactttcgaaggcaagttacgtccagtgaactacctttcagttgggaatgcaaacgcatacgaagaaggaaaaatcagt 197 F K T F E G K L R P V N Y L S V G N A N A Y E E G K I S 2536 gataggcttcttgaaaagttgggatggctttgggataaagtgtatgaagacccagctttcaacaatgttcgacctttaccgcaa 225 D R L L E K L G W L W D K V Y E D P A F N N V R P L P Q 2620 cttcatacacttgtttatgataataaaagaggagtataa 2658 253 L H T L V Y D N K R G V * dplORF021 2504 atgcaaacgcatacgaagaaggaaaaatcagtgataggcttcttgaaaagttgggatggctttgggataaagtgatgaagac 1 M Q T H T K K E K S V I G F L K S W D G F G I K H K T 2588 cagctttcaacaatgttcgacctttaccgcaacttcatacacttgtttatgataataaaagaggagtataaaatgaaaattgag 29 Q L S T M F D L Y R N F I H L F M I I K E E Y K M K I E 2672 catctagataaaatcggtaacgtattagggagagagaacggatgggcttcccttaagccggatgaaattgtaaccttggacaat 57 H L D K I G N V L G R E N G W A S L K P D E I V T L D N 2756 actgaggcagccgttcaaagactttttggtctattaggcgaggacgcagaacgtgacgggttgcaagatactccattccgtttt 85 T E A A V Q R L F G L L G E D A E R D G L Q D T P F R F WO 00/32825 PCT/IB99/02040 373 2840 gttaaagcactcgctgaacataccgtagggtatcgagaagaccctaaacttcatctcgaaaaaacattcgacgtcgaccatgaa 113 V K A L A E H T V G Y R E D P K L H L E K T F D V D H E 2924 gaccttgttcttgtgaaagacattccattcaattctttatgtgagcatcatttagctccgttcgtagggaaggtgcatattgca 141 D L V L V K D I P F N S L C E H H L A P F V G K V H I A 3008 tacattcctaaggataagattacaggtctttcaaaattcggtcgagtggttgaaggatacgctaaacgacttcaagtacaagag 169 Y I P K D K I T G L S K F G R V V E G Y A K R L Q V Q E 3092 cgcttgactcaacaaatcgctgacgctattcaggaagttctaaatcctcaagcagttgcggtcatcgtagaggctgagcatact 197 R L T Q Q I A D A I Q E V L N P Q A V A V I V E A E H T 3176 tgcatgagcggacgcggtattaagaagcacggggcaacgacagtgacttcaactatgcgaggtcttttccaagatgacgcatct 225 C M S G R G I K K H G A T T V T S T M R G L F Q D D A S 3260 gctcgagcagaattgcttcagttgattaaaaagtag 3295 253 A R A E L L Q L I K K * dplORF022 30896 atgagtaaagacattctttacggaatcaagctcgtgcaaatcgaggagcttgacccattgactcagttgccaaaagtcggcgga 1 M S K D I L Y G I K L V Q I E E L D P L T Q L P K V G G 30980 gctaactttgtcgtagatacggcagaaacagcagaactcgaagccgtgacctcggagggaactgaagatgtgaaacgcaatgac 29 A N F V V D T A E T A E L E A V T S E G T E D V K R N D 31064 acgcgcattcttgctatcgtgcgtactccagaccttttatacggttatgacttaacattcaaggacaacacgtttgaccctgaa 57 T R I L A I V R T P D L L Y G Y D L T F K D N T F D P E 31148 atcatggccctaattgaaggtggtacagtacgtcaacaaggcggaactattgctggatacgacaccccaatgcttgcacaaggt 85 I M A L I E G G T V R Q Q G G T I A G Y D T P M L A Q G 31232 gcttctaatatgaaaccatttagaatgaacatctatgtgccaaactatgtaggtgactcaattgtcaactacgtgaaaatcact 113 A S N M K P F R M N I Y V P N Y V G D S I V N Y V K I T 31316 ttgaataactgtaccggtaaagctccagggctttcaatcgggaaagagttctacgctcctgagttcaacatcaaggcacgtgaa 141 L N N C T G K A P G L S I G K E F Y A P E F N I K A R E 31400 gcaaccaaagcaggtttgccagttaagtcaatggactatgtggcacaacttccagcggttcttcgtcgcgtgacattcgatttg 169 A T K A G L P V K S M D Y V A Q L P A V L R R V T F D L 31484 aacggtggaacaggaaccgccgacgcagttcgagttgaagcaggtaagaagatttctccaaaaccagttgaccctaccttaaca 197 N G G T G T A D A V R V E A G K K I S P K P V D P T L T 31568 ggtaaggctttcaaaggctggaaagttgaaggagaatcaactatttgggacttcgacaaccacatgatgcctgaccgagacgtc 225 G K A F K G W K V E G E S T I W D F D N H M M P D R D V 31652 aaactcgtagcacaatttgcatag 31675 253 K L V A Q F A * dplORF023 6419 atggccaagtccaatttaactagaattgcaaagatggttagagcaggaaacagtgaaggtcctgcttcatcttttgtcaattcg 1 M A K S N L T R I A K M V R A G N S E G P A S S F V N S 6503 ctgacccgggttattgaacgaactcagcctgaatataatccttcgacatattataagcccagcggggttggtggatgtattcga 29 L T R V I E R T Q P E Y N P S T Y Y K P S G V G G C I R 6587 aaaatgtatttcgaaagaatcggtgagtctattatagataacgcagattctaacctaattgcaatgggcgaagctggaacattt 57 K M Y F E R I G E S I I D N A D S N L I A M G E A G T F 6671 aggcacgaagttctccaagagtacatggttaaaatggctgaaatcgatgaggactttgaatggttgaatgtagcagagttcttg 85 R H E V L Q E Y M V K M A E I D E D F E W L N V A E F L 6755 aaagaaaatccagttgaaggaactatcgtcgacgagcgtttcaagaaaaacgattatgaaacgaagtgtaagaacgaacttctt 113 K E N P V E G T I V D E R F K K N D Y E T K C K N E L L 6839 caactttcattcttgtgtgacggactagttcgatataaaggcaagctctacattttagagattaagactgaaaccatgttcaag 141 Q L S F L C D G L V R Y K G K L Y I L E I K T E T M F K 6923 ttcactaaacatactgagccctatgaagaacacaagatgcaagcaacttgctacggaatgtgtctaggagtcgatgatgtcatt 169 F T K H T E P Y E E H K M Q A T C Y G M C L G V D D V I 7007 ttcctttatgaaaatcgagataacttcgaaaagaaagcctacacgtttcacatcacagacgagatgaaaaatcaagtccttgga 197 F L Y E N R D N F E K K A Y T F H I T D E M K N Q V L G 7091 aaaattatgacctgcgaagagtatgtagagaaaggcgaaagtcctaaaatctattgctcttcagcctattgcccatattgtaga 225 K I M T C E E Y V E K G E S P K I Y C S S A Y C P Y C R 7175 aaggaaggtcgaaatctgtga 7195 253 K E G R N L * dplORF024 25992 atgaacgcagtagatggccaggtagttcatattctacaagtattagcagaagatggaaatgctacggctgaaaagttcgaaaag 1 M N A V D G Q V V H I L Q V L A E D G N A T A E K F E K 26076 gaagtcagggctgcatctttagtattttcacgaagagcagccgaggcagttgtcaaaggtgaaatctataaggacggcaaaaac 29 E V R A A S L V F S R R A A E A V V K G E I Y K D G K N 26160 ctctcgaaacgtgtttggtcttcagccgcacgcgcaggaaatgatgttcaacaaatagtcacacaaggcctagcaagtggaatg 57 L S K R V W S S A A R A G N D V Q Q I V T Q G L A S G M 26244 tctgctacagatatggctaaaatgctcgagaaatatatcgaccctaaggttcgaaaagattgggactttgataagatagctgag 85 S A T D M A K M L E K Y I D P K V R K D W D F D K I A E 26328 aagctagggaaacctgctgctcataaatatcaaaatctcgaatacaatgcccttcgacttgctcgaactaccattagccattcc 113 K L G K P A A H K Y Q N L E Y N A L R L A R T T I S H S 26412 gccacagctggagtgagacaatggggcaaggttaatccttatgctcgaaaagttcaatggcattctgttcacgctccaggtcga 141 A T A G V R Q W G K V N P Y A R K V Q W H S V H A P G R 26496 acgtgtcaagcgtgtatcgatttagatggtgaagtatttcctatcgaagaatgtcctttcgaccatcctaatggaatgtgctac 169 T C Q A C I D L D G E V F P I E E C P F D H P N G--M C ) 26580 caaactgtatggtacgaaaactcactcgaagaaatcgctgatgagttgagaggctgggtagacggagaacctaatgatg tatta 197 Q T V W Y E N S L E E I A D E L R G W V D G E P 1- D V L 26664 gacgaatggtacgacgatttaagttcaggaaaagttgagaaatacagcgacctcgactttgttaaaagttattag 26738 225 D E W Y D D L S S G K V E K Y S D L D F V K S V * dplORF025 18778 atggcaaagaacaaaaagcgaaaaaaagtaaatgtcaaaaggaaaatgcttatccctacaaatctctcgaaaaaagtaaatgta 1 M A K N K K R K K V N V K R K M L I P T N L S K K V N V WO 00/32825 PCT/I B99/02040 374 18694 aaagcaatcgcttatagaaaagtcactgttaagtggctgcctaatacagatgaaattcaagtatatttcgacctttatataaat 29 K A I A Y R K V T V K W L P N T D E I Q V Y F D L Y I N 18610 aaaaacaggctgacaatgttaggcactattgacccggacaagagctattttgaaggaattaggattgtttgtaagaaacctcag 57 K N R L T M L G T I D P D K S Y F E G I R I V C K K P Q 18526 ccttggatgactgttaaggagctccaggttgcgcgtgcagacgccccaggtttttttgcagttcttaaagcctattgtcacacg 85 P W M T V K E L Q V A R A D A P G F F A V L K A Y C H T 18442 gttggcgatgtactagatagcggagcagagcctactgaaattgttcaaggtattatgtataaagacggtgaactatttaaggac 113 V G D V L D S G A E P T E I V Q G I M Y K D G E L F K D 18358 agtgaaattgtcagccttttcaaatacgatgtcaaagagccttatgagtttccaaaggaccttcctataaccttggacaacttt 141 S E I V S L F K Y D V K E P Y E F P K D L P I T L D N F 18274 ttagagttcattatgtctagccagcatactagagcacttgttttgcgttgtgctaatataggtgagttttccaagaattggcgg 169 L E F I M S S Q H T R A L V L R C A N I G E F S K N W R 18190 aaatggcaaaaagctatccagctcctgctcgactatgccaaggcggatgactttaaagtagacgaaactgtttgggacttttca 197 K W Q K A I Q L L L D Y A K A D D F K V D E T V W D F S 18106 cccggctctaaagctggaaaggtagcacgtcgtaaaggctatgaggcaattcaacaagcccttgagcagataaataaataa 18026 225 P G S K A G K V A R R K G Y E A I Q Q A L E Q I N K * dplORF026 21512 atggcgaaagctactggaccaaaagttcgaagaggaaaaactcctccacggccaaaagacaaaaaaggaatcaaagcaaatgcg 1 M A K A T G P K V R R G K T P P R P K D K K G I K A N A 21596 cgtgtcaataaagaccagttcgtagagtatgactataaaggcatcaagatgacaattaaggaacgtgatgctagaatgaaattg 29 R V N K D Q F V E Y D Y K G I K M T I K E R D A R M K L 21680 gaatttattagaggcatgactattcaggaaattgcagcccgctatggattaaatgaaaagcgtgttggcgaaatacgggctcgc 57 E F I R G M T I Q E I A A R Y G L N E K R V G E I R A R 21764 gataaatgggtgaaggctaagaaagagttcgagaatgaaaaggctcttgttactaatgatacattgactcaaatgtatgcaggg 85 D K W V K A K K E F E N E K A L V T N D T L T Q M Y A G 21848 tttaaagtctcagtcaatattaaatatcacgccgcctgggagaaactaatgaacatcgtcgaaatgtgtttagataatcctgac 113 F K V S V N I K Y H A A W E K L M N I V E M C L D N P D 21932 agatatttatttactaaagaaggaaatattagatggggcgcattagatgtcctttcgaaccttatagatagagctcaaaaagga 141 R Y L F T K E G N I R W G A L D V L S N L I D R A Q K G 22016 caagaaagagcgaatggaatgcttccggaagaggttcgatatagactacaaattgagcgcgagaaaattacattgctccgggcc 169 Q E R A N G M L P E E V R Y R L Q I E R E K I T L L R A 22100 aaaatgggcgaccaggaaattgaaggcgaggttaaagataacttcgtagaagcactagataaagcagctcaagccgtttggcaa 197 K M G D Q E I E G E V K D N F V E A L D K A A Q A V W Q 22184 gaatttagtgacgcaacaggttcctacattaaaggagtgactgataatgacaataagcctgagaaataa 22252 225 E F S D A T G S Y I K G V T D N D N K P E K * dplORF027 52762 atgggaaaagtatcaattcaaaaatcaggaacatttagctcagggtctaataacgagtttttcacactcgctgaccacggtgac 1 M G K V S I Q K S G T F S S G S N N E F F T L A D H G D 52846 agcgcaattgtcactctattgtatgatgacccggaaggcgaagacatggattatttcgtagtccacgaagcagacgttgacggt 29 S A I V T L L Y D D P E G E D M D Y F V V H E A D V D G 52930 cgtcgacgctatatcaattgcaatgctattggcgaagacggggaaacagtccatcctgataattgtccattatgccaaaacgga 57 R R R Y I N C N A I G E D G E T V H P D N C P L C Q N G 53014 ttccctcgtattgaaaaactatttcttcaactttacaaccatgatacgggaaaagttgaaacatgggaccgaggccgttcttat 85 F P R I E K L F L Q L Y N H D T G K V E T W D R G R S Y 53098 gttcaaaagattgttacatttatcaataaatatggaagccttgtgactcagccttttgaaattattcgttcaggagctaaaggt 113 V Q K I V T F I N K Y G S L V T Q P F E I I R S G A K G 53182 gaccaacgaactacttatgaattccttccagagcgtccggaagacagtgctactcttgaagattttccagaaaagagcgaactt 141 D Q R T T Y E F L P E R P E D S A T L E D F P E K S E L 53266 cttggaactctaattttagacctcgacgaagaccaaatgtttgacgtggttgacggcaagttcactcttcaagaagagcgttct 169 L G T L I L D L D E D Q M F D V V D G K F T L Q E E R S 53350 tcaagtcgttcaaattcacgtagaggagcatctcctgcgcctagacgaggttccggtcgagaatcttcacaaggtcgaacagct 197 S S R S N S R R G A S P A P R R G S G R E S S Q G R T A 53434 gaaagaactccttcagttagtcgaagaactcctccaacacgaggtcgaggattctaa 53490 225 E R T P S V S R R T P P T R G R G F * dplORF028 44595 atgtcaaaaattaaattcgaaaaccttaaaaaaggcgatgttgtgctacgagctaaatctcaaacgaagtttaaaatcgtttca 1 M S K I K F E N L K K G D V V L R A K S Q T K F K I V S 44679 attttagcagacgaaaagaaagcagaccttgaatcattagaagacggaggtgaacttcacctttcagcttcaactctcgaacgt 29 I L A D E K K A D L E S L E D G G E L H L S A S T L E R 44763 tggtacacaatggaagatgaaactgaacctaaaaaagaagaagctgctaaacctgctaaaaaggctgctcctgcagttgctcga 57 W Y T M E D E T E P K K E E A A K P A K K A A P A V A R 44847 cctgctcgaaaaggtagagtcgttcccaaacctaaaaaagaagtccttgaggaagaaattcctgaagttaaggaacagccggaa 85 P A R K G R V V P K P K K E V L E E E I P E V K E Q P E 44931 gaagttggttcagttagtgagaaatctactgttcgaaaacctgctcctaaaaaagaaagcgtgatggcgattactaaggctctt 113 E V G S V S E K S T V R K P A P K K E S V M A I T K A L 45015 gaaagtcgaattgttgaagcctttcctgcgtctactcgaatcgtcactcagtcttacatcgcctatcgctctaagaagaacttc 141 E S R I V E A F P A S T R I V T Q S Y I A Y R S K K N F 45099 gttactatcgaagaaactcgaaaaggtgtttctattggagttcgcgcaaaagggttgacagaagaccaaaagaaachecttgca 169 V T I E E T R K G V S I G V R A K G L T E D Q K.K L L A 45183 tctattgctcctgcatcttacgaatgggcgattgacggaatttttaaactcgtcaaggaagaagatattgacaccgcaatggaa 197 S I A P A S Y E W A I D G I F K L V K E E D I D T A M E 45267 ttgattgaagcttctcacctttcttcgctatga 45299 225 L I E A S H L S S L * dplORF029 WO 00/32825 PCT/IB99/02040 375 662 atgaaatcagtagttttattatccggcggagtcgactcagccacttgtttagcaattgaagttgacaagtggggttctaaaaat 1 M K S V V L L S G G V D S A T C L A I E V D K W G S K N 746 gttcatgctatagcattcaattacggacaaaagcatgaagcagaacttgaaaatgctgctaatgttgcaatgttctacggagtc 29 V H A I A F N Y G Q K H E A E L E N A A N V A M F Y G V 830 aagttcaccattcttgaaattgactcgaaaatctactcaagctctagctcttccttattacaaggaaaaggcgaaatttcacat 57 K F T I L E I D S K I Y S S S S S S L L Q G K G E I S H 914 ggaaaatcttacgctgaaatcctagcagagaaggaagtagttgacacctatgttccatttagaaatggactaatgctttcacag 85 G K S Y A E I L A E K E V V D T Y V P F R N G L M L S Q 998 gctgcggcttatgcttattcggttggagcttcttacgtcgtatatggtgctcacgcagacgatgcggctggaggtgcttaccct 113 A A A Y A Y S V G A S Y V V Y G A H A D D A A G G A Y P 1082 gattgcactcctgagttctataattcaatgtcaaatgcaatggaatatggaactggaggcaaggtaacccttgtcgctcctcta 141 D C T P E F Y N S M S N A M E Y G T G G K V T L V A P L 1166 cttactctaaccaaggcgcaagtcgttaaatggggaattgatttagatgttccttatttcttgactcgttcatgttatgaaagt 169 L T L T K A Q V V K W G I D L D V P Y F L T R S C Y E S 1250 gacgctgaaagttgtggaacttgcgcaacttgtatcgaccgcaaaaaggcattcgaagaaaatggaatgactgaccctattcat 197 D A E S C G T C A T C I D R K K A F E E N G M T D P I H 1334 tataaggagaattga 1348 225 Y K E N * dplORF030 20088 atgaataacgaaaaaattattgaaaaaattaaaaatcttattcaattagcaaatgacaacccgagtgacgaagaggggcaaact 1 M N N E K I I E K I K N L I Q L A N D N P S D E E G Q T 20004 gcccttcttatggctcaaaagttgatgctaaagaataatatcgcacttgctcaagttgaacaatttgatgaacctaaacagttc 29 A L L M A Q K L M L K N N I A L A Q V E Q F D E P K Q F 19920 gagacttetcaagctgttgggaaagaagcaggtcgaatattttggtgggaacgtgaacttggtcatattctcgcgactaatttt 57 E T S Q A V G K E A G R I F W W E R E L G H I L A T N F 19836 aggtgcttttgtattaatcagcgtgatatgcgcttgaataaaagtcgaataattttcttcggcgaaaaacaagacgctgaatta 85 R C F C I N Q R D M R L N K S R I I F F G E K Q D A E L 19752 gtgtctaaaatatatgaggctgctttgctttatcttcgttaccgtattgaccgacttcctactcgcgaaccttcctacaagaat 113 V S K I Y E A A L L Y L R Y R I D R L P T R E P S Y K N 19668 tcatacctcaaaggctttttgtcagccttagccattcgatttaaaaagcaggtggaagaatattcacttatggtcctacctagc 141 S Y L K G F L S A L A I R F K K Q V E E Y S L M V L P S 19584 gagcaaacaaaaaatgcgcttcaggacacatttcgaaatttaaagaaggaaggaattgacagacctcaacatgacttcaatett 169 E Q T K N A L Q D T F R N L K K E G I D R P Q H D F N L 19500 gaagcgtatattgaagggcggtttcatggcgagaatgcaaagattatgcccgatgaaattttggaaggcggtaactaa 19423 197 E A Y I E G R F H G E N A K I M P D E I L E G G N * dplORF031 26943 atggcttatcaattagaagacttgttaaaaggtctagatgaaccaactatcaaacaggtgaaggaaattatttegaaaacttcg 1 M A Y Q L E D L L K G L D E P T I K Q V K E I I S K T S 27027 aaagaactcgatgctaaaattttcattgacggcgacggtcaacattttgtacctcacgcacgtttcgatgaagttgttcaacag 29 K E L D A K I F I D G D G Q H F V P H A R F D E V V Q Q 27111 cgcgatgcagctaacggctcaattaattcttataaagaacaagtcgcgacgctttctaaacaggtcaaagataacggtgatgcg 57 R D A A N G S I N S Y K E Q V A T L S K Q V K D N G D A 27195 cagaccactatccaaaaccttcaagagcaactcgacaagcagtctcaacttgcaaaaggagctgtgattacttcagctcttcat 85 Q T T I Q N L Q E Q L D K Q S Q L A K G A V I T S A L H 27279 ccgttgattagtgactccattgctccagcagcagacattcttggatttatgaaccttgacaacattacggtcgaaagtgacggt 113 P L I S D S I A P A A D I L G F M N L D N I T V E S D G 27363 aaagttaaaggtcttgatgaagagttgaaagctgttcgtgagtctcgtaaatacttattcaaagaagtcgaagttcccgcagaa 141 K V K G L D E E L K A V R E S R K Y L F K E V E V P A E 27447 caagaggetcaagctaagtcgccagccgggactggaaatttaggaaatccaggtcgtgtcggtggtggtgttcccgaacctcgt 169 Q E A Q A K S P A G T G N L G N P G R V G G G V P E P R 27531 gaaatcggetcttttggtaagcaacttgctgctgctcaacaaacggcaggagcacaagaacaatcatcattctttaaataa 27611 197 E I G S F G K Q L A A A Q Q T A G A Q E Q S S F F K * dplORF032 52033 atgaaagaagcgaatagactagtttctagctatgtaggattcgaatgctggactgacgaagaatgtatcaggaactttgaacta 1 M K E A N R L V S S Y V G F E C W T D E E C I R N F E L 52117 gaccctgatatgtcaattgcgtctgcttatcatcgttattttgggatgctttattcctatgcaaaaaggtttaaatgcttatct 29 D P D M S I A S A Y H R Y F G M L Y S Y A K R F K C L S 52201 cgacatgacattgaaagcattgcattcgagactatttcaaaatgtttggcaacgttcaaatcaaaccaaggggccaagttttca 57 R H D I E S I A F E T I S K C L A T F K S N Q G A K F S 52285 acttaccttacaagactcttcaagaatagaatagtcttagaatataggtacctaaatgcaccttccatgaatcgaaattggtat 85 T Y L T R L F K N R I V L E Y R Y L N A P S M N R N W Y 52369 gtagaagtgacgttcgatagcgtttcgacaaatgaagaaggcgacgattttagtatcctatcgacagttggctattgtgaagac 113 V E V T F D S V S T N E E G D D F S I L S T V G Y C E D 52453 tacggaaaaattgaaattgaagcaagtcttgacttcatgacgctttctaatacagagtatgcttatatctcgtctgtcattcaa 141 Y G K I E I E A S L D F M T L S N T E Y A Y I S S V I Q 52537 aacggtccttcagtaagcgacgcagaaattgcgcgtgaaattggagtaagcaggtetgctattagtcagtctaagaagtcacta 169 N G P S V S D A E I A R E I G V S R S A I S Q S KLK--S L 52621 aaaaataaattaaaagattttatataa 52647 197 K N K L K D F I * dplORF033 7670 atggcaagacctaagttacctcaaattgatattegagaagaagaaatacgagatgctcaagacgtagcagactcgtatggtgcg 1 M A R P K L P Q I D I R E E E I R D A Q D V A D S Y G A 7754 attatcaataaagtagtcgacgaaattgttgaagcagettgeggttcacttgaccaggcaatggaagaaattcaaatagttgta WO 00/32825 PCT/IB99/02040 376 29 I I N K V V D E I V E A A C G S L D Q A M E E I Q I V V 7838 agccaaaatcctgtcattatggaagaccttaactactacattggctatcttcccactcttctttatttcgccgcagatagggcg 57 S Q N P V I M E D L N Y Y I G Y L P T L L Y F A A D R A 7922 gaaatggtgggaatacaaatggattcaagttCtgctatCaggaaagaaaaatacgataatctatacattttagccgccgggaaa 85 E M V G I Q M D S S S A I R K E K Y D N L Y I L A A G K 8006 actattcctgacaagcaagcagaaactcgaaaaCttgtcatgaatgaagaagtcatcgaaaatgcttacaagcgagcctacaag 113 T I P D K Q A E T R K L V M N E E V I E N A Y K R A Y K 8090 aaagttcaattaaagctagaacaggccgataaggtattagcatctttaaaacgaattcaaacctggcaactagcagagttagaa 141 K V Q L K L E Q A D K V L A S L K R I Q T W Q L A E L E 8174 actcagtcaaataattcaaaaggagtattattaaatgcaaaaagacgtagacgtgaaaatgattga 8239 169 T Q S N N S K G V L L N A K R R R R E N D * dplORF034 131 atgagtcaaaacactacacgcactgacgctgaattgacaggcgttactcttttaggaaaccaagacaccaaatacgattatgac 1 M S Q N T T R T D A E L T G V T L L G N Q D T K Y D Y D 215 tataatccagacgtccttgaaactttccctaacaaacatcctgaaaataattacctagtaacatttgacggatatgaattcact 29 Y N P D V L E T F P N K H P E N N Y L V T F D G Y E F T 299 tccctttgccctaaaacaggacagcctgacttcgcgaatgttttcattagttacattccaaacgaaaagatggttgaatctaaa 57 S L C P K T G Q P D F A N V F I S Y I P N E K M V E S K 383 tcattgaaattgtacttattcagtttccgtaaccacggtgacttccacgaagattgcatgaacattattttgaatgacttgtat 85 S L K L Y L F S F R N H G D F H E D C M N I I L N D L Y 467 gaattgatggaacctaagtacattgaagtcatgggcctattcactcctcgtggtggaatttcaatttacccattcgtcaacaaa 113 E L M E P K Y I E V M G L F T P R G G I S I Y P F V N K 551 gtgaatcctcaatttgcaactcctgaacttgaacagcttcaacttcaacgcaaattgaacttccttggaaatgttcaaggtctt 141 V N P Q F A T P E L E Q L Q L Q R K L N F L G N V Q G L 635 ggacgagctattcgatag 652 169 G R A I R * dplORF035 17425 atgcacctaatgaaggattcgaagatgttgaggacatggaagtccttagcattcgagttcgaaacgaaggtgaggacgacgagt 1 M H L M K D S K M L R T W K S L A F E F E T K V R T T S 17341 gggttgaagttatcgcctgctatgaaaacgatgacgaggacgaagatttggaagggttataaaatgaaggtatttatcaacaat 29 G L K L S P A M K T M T R T K I W K G Y K M K V F I N N 17257 catactgaagctgatattgactacaaagatattctaaattttgtagcttatcgaaactctcctaaccctcaaattcaaatcact 57 H T E A D I D Y K D I L N F V A Y R N S P N P Q I Q I T 17173 agctggaacgctttgctttcctgctatacacggaatgagctttcttataaaggagtttcaataacggacttttttgaagccatt 85 S W N A L L S C Y T R N E L S Y K G V S I T D F F E A I 17089 caaactattgcaagttccttcactcacctagactcgaaaacaattgatacacaaaatgaaaagcgactcgaaaggattgaggaa 113 Q T I A S S F T H L D S K T I D T Q N E K R L E R I E E 17005 cttcagtcaagaataggtcattgtaactgtactatcgacgaacttaaaaaaggagtccacgaaatgccggatattgaatcagct 141 L Q S R I G H C N C T I D E L K K G V H E M P D I E S A 16921 atttcttaccagtacggacagattcttgcttatgaagatgaaCttaattttctgctaaactaa 16859 169 I S Y Q Y G Q I L A Y E D E L N F L L N * dplORF036 48808 gtgttagtcgaacgaaaagccgacaaggaatgttgggaatggctagaagctgttcgagcaaatatagtcgaagaagttcgaaac 1 V L V E R K A D K E C W E W L E A V R A N I V E E V R N 48892 ggtcttagcattgttattgcttcgaataCtgtcgggaatgggaaaactagctgggcggttcgacttttgcaacgctatttagca 29 G L S I V I A S N T V G N G K T S W A V R L L Q R Y L A 48976 gaaactgcacttgacggaagaattgttgagaaaggaatgtttgtagtgtcagctcaactattgactgagttcggcgactataat 57 E T A L D G R I V E K G M F V V S A Q L L T E F G D Y N 49060 tattttcaaaccatgcaagaatttctcgaacgtttcgagcgccttaagacttgtgagctattagtcatagacgaaataggtgga 85 Y F Q T M Q E F L E R F E R L K T C E L L V I D E I G G 49144 ggttccttaaccaaggcctcttatccttatctgtatgacttggttaattatagggttgacaataacttgtcgactatttatacg 113 G S L T K A S Y P Y L Y D L V N Y R V D N N L S T I Y T 49228 actaattatactgacgatgaaattattgaccttttaggccaaaggctttatagtcgtatatatgatacttcagtggttctagat 141 T N Y T D D E I I D L L G Q R L Y S R I Y D T S V V L D 49312 tttcaggcaagcaatgtaagaggattggaggtaagcgaaattgaatcatag 49362 169 F Q A S N V R G L E V S E I E S * dplORF037 55855 atggtgaagaaattgaaatctaaaatctattcagttgcatatataattctagtagttattgcgaaccttgtgacaatttatttc 1 M V K K L K S K I Y S V A Y I I L V V I A N L V T I Y F 55939 gaacctttaaatgtgaaaggaattttaattcctccaagcagttggtttatgggattcactttcctgcttataaatctaataagc 29 E P L N V K G I L I P P S S W F M G F T F L L I N L I S 56023 aagtacgagaagccaaaatttgcaggttctttgatatgggtagggttattccttacctcgttgatttgctttatgcaaaaccta 57 K Y E K P K F A G S L I W V G L F L T S L I C F M Q N L 56107 ccacaatcgcttgtcgtggcttcaggagttgcattttggataagtcaaaaagcaagtgtctttatattcgacaagctctcgaat 85 P Q S L V V A S G V A F W I S Q K A S V F I F D K L S N 56191 aaattagactcgaagattgcaaatgctttgtctagcaacatcggttctattatagacgcaaccatatggatttcattaggactg 113 K L D S K I A N A L S S N I G S I I D A T I W I S L G L 56275 agtcctcttggaattggaacggttgcatatatagatattccgtcagccgtactaggccaagttctagttcagtttatcttgcag 141 S P L G I G T V A Y I D I P S A V L G Q V L V Q F I LQ 56359 tcaattgcttcgagatatttgaaaaagtag 56388 169 S I A S R Y L K K * dplORF038 1350 atgagagtttctaaaaccttaacattcgacgcagctcatcaactagttggacattttggaaaatgcgcaaatttgcacgggcat 1 M R V S K T L T F D A A H Q L V G H F G K C A N L H G H 1434 acttacaaagtcgaaatttcattagcaggcggaacttatgaccacggttcgagtcaagggatggttgttgacttttatcacgtc 29 T Y K V E I S L A G G T Y D H G S S Q G M V V D F Y H V WO 00/32825 PCT/IB99/02040 377 1518 aagaaaatcgcaggtacattcattgacagacttgaccacgctgttcttcttcaagggaatgaaccaatcgctttagcaaatgca 57 K K I A G T F I D R L D H A V L L Q G N E P I A L A N A 1602 gttgacaccaagcgagttctatttggatttagaactacggctgagaatatgtcaagattccttacctggactctcacggagtt 85 V D T K R V L F G F R T T A E N M S R F L T W T L T E L 1686 atgtggaagcatgctcgtatcgactctatcaaactatgggaaactcctacaggttgcgcagaatgtacttactacgagattttc 113 M W K H A R I D S I K L W E T P T G C A E C T Y Y E I F 1770 acagaagacgagattgaaatgttcaagaacgtaacctttatcgacaaagacgaaaagattactgtccgcgaaattttagagcag 141 T E D E I E M F K N V T F I D K D E K I T V R E I L E Q 1854 gagcaggataatggttaa 1871 169 E Q D N G * dplORF039 3306 atgaataaaagtgcaaccttttggcttgttcgaacagctcttattgcggctctatatgtgacattgaccgttgcattttctgct 1 M N K S A T F W L V R T A L I A A L Y V T L T V A F S A 3390 attagttatggacctattcaatttagagtcagtgaagccttgattcttctacctttatggaaccatagatggactccggggatt 29 I S Y G P I Q F R V S E A L I L L P L W N H R W T P G I 3474 gtattaggaacaattattgcaaacttcttttcacctcttggactgattgacgttttattcggttcacttgctaccttccttgga 57 V L G T I I A N F F S P L G L I D V L F G S L A T F L G 3558 gtagtggcaatggtgaaagttgctaagatggcaagtcctctatattcacttatctgtccagttcttgctaatgcttaccttatt 85 V V A M V K V A K M A S P L Y S L I C P V L A N A Y L I 3642 gcgctggaacttcgaatagtttactctttacctttttgggaatctgtcatctatgtaggaattagtgaagcgattatcgtttta 113 A L E L R I V Y S L P F W E S V I Y V G I S E A I I V L 3726 atttcatacttccttatttccacgctggcgaagaacaatcattttagaacactgataggagcgaaaaatgggatttaa 3803 141 I S Y F L I S T L A K N N H F R T L I G A K N G I * dplORF040 7192 gtgagctatactggaaaaatgttcgaggaagactttttcgaaggtgcaaaagactttgagaaagatgctttcacggtccgtcta 1 V S Y T G K M F E E D F F E G A K D F E K D A F T V R L 7276 tatgataccactaatggatttcgaggagttgcaaatccctgcgattatatagccgcaactaactttgggaccttgtttattgaa 29 Y D T T N G F R G V A N P C D Y I A A T N F G T L F I E 7360 ctgaaaactactaaagaagcttctttgagctttaataacatcactgataatcaatggttccagctatcacgcgcagatggatgc 57 L K T T K E A S L S F N N I T D N Q W F Q L S R A D G C 7444 aaatttattctcgccggaattttagtgtatttccaaaagcatgaaaagattatatggtatccaatttcaagccttgaaaaaatt 85 K F I L A G I L V Y F Q K H E K I I W Y P I S S L E K I 7528 aaacggtctggagttaaaagcgtcaacccaaacttcatcgatgcagggtatgaagtttcttacaagaagcgtcgaactagattg 113 K R S G V K S V N P N F I D A G Y E V S Y K K R R T R L 7612 accattcctttccaaaatgttctagatgcagttgagcttcattacaaggagaaaagcaatggcaagacctaa 7683 141 T I P F Q N V L D A V E L H Y K E K S N G K T * dplORF041 8208 atgcaaaaagacgtagacgtgaaaatgattgaccctaaacttgaccgattaaaatacacaggtgattgggttgatgtacgaatt 1 M Q K D V D V K M I D P K L D R L K Y T G D W V D V R I 8292 agttctatcactaaaattgacgccgacagcgccgatgtctcaagatgtcgaaaagtgcttcaaaaggctcaagtatattcagtg 29 S S I T K I D A D S A D V S R C R K V L Q K A Q V Y S V 8376 gcggcaggtgaatgcattaaaattgcacacggatttgctcttgaacttcctaagggatatgaagcaatcttgcatcctcgttcc 57 A A G E C I K I A H G F A L E L P K G Y E A I L H P R S 8460 agtctttttaagaaaactggtctaatcttcgtttctagcggagtgattgacgaaggttacaaaggtgacactgatgaatggttc 85 S L F K K T G L I F V S S G V I D E G Y K G D T D E W F 8544 tcagtttggtatgctactcgtgacgcagatatcttctacgaccaaagaattgcccaatttagaattcaggaaaagcaacctgct 113 S V W Y A T R D A D I F Y D Q R I A Q F R I Q E K Q P A 8628 atcaagttcaatttcgtagaatctttaggaaatgcggctcgtggaggccatggaagtacaggtgatttctaa 8699 141 I K F N F V E S L G N A A R G G H G S T G D F * dplORF042 48082 gtggcaaggcaaagaataggcaattcaggaaagcctaaaaatgaaattgaactaacattcaaagacaagcctaaaactcgttct 1 V A R Q R I G N S G K P K N E I E L T F K D K P K T R S 48166 accttattcaagaaggacgtggcaacaggtctttcaaaagtcgagcatgattattttcaaatagttgaagcacttaacggaaaa 29 T L F K K D V A T G L S K V E H D Y F Q I V E A L N G K 48250 caattcgaacctaatatgaagcaggtgtcatctttctttatagttcagtatgaatttattttcaatattaagtgcatcgattat 57 Q F E P N M K Q V S S F F I V Q Y E F I F N I K C I D Y 48334 aactggttcaacttttcgagcactatgaaaaatgttcgaacttatttaaacattgagtcgaacattgaactttgtcgattttta 85 N W F N F S S T M K N V R T Y L N I E S N I E L C R F L 48418 gctgaaagttttgttaaatatgaaaatgttcgaaaaagattgaacctaagcgaaaggttcataacggtctcgactttcaaaaga 113 A E S F V K Y E N V R K R L N L S E R F I T V S T F K R 48502 gcctggattttggacgaactcgaaggaaaaacgggttcaaaattcgaaggattttattag 48561 141 A W I L D E L E G K T G S K F E G F Y * dplORF043 31699 atgactaatattatcacagctgagcagtttaagcaacttgcatttcaaatcatcgcacttccaggattttcaaaaggtagtgaa 1 M T N I I T A E Q F K Q L A F Q I I A L P G F S K G S E 31783 cctatccatgttaaaattcgagcagcaggtgtcatgaacctaatcgctaacgggaaaatccctaatacgcttttaggtaaagtg 29 P I H V K I R A A G V M N L I A N G K I P N T L L G K V 31867 acagaactgtttggagaaacttcgacagtcactaaagacaatgctagtctagcatcaattactgaccaacagaagaaagaggcg 57 T E L F G E T S T V T K D N A S L A S I T D Q- Q K.-K'"E A 31951 ctcgaccgattgaacaaaaccgataccggtattcaagacatggctgaacttcttcgagtattcgcagaagttcaatggtagag 85 L D R L N K T D T G I Q D M A E L L R V F A E A S M V E 32035 cctacttacgctgaagtcggcgagtatatgacagatgagcaacttatgacaatcttcagtgcaatgtacggtgaagtgactcaa 113 P T Y A E V G E Y M T D E Q L M T I F S A M Y G E V T Q 32119 gctgaaacctttcgtacagacgaaggaaatgtctaa 32154 141 A E T F R T D E G N V * WO 00/32825 PCT/IB99/02040 378 dplORF044 25666 atggtaagtgttttgattagcagcagctcctttttgaagttcctgcttcattttagctcgacaagtatttctaaatcgaataag 1 M V S V L I S S S S F L K F L L H F S S T S I S K S N K 25582 gttttcaatttccttgtttcctacataagtggtgaaccgataatggcacttaggacattcgaagaatctccactctacgccctt 29 V F N F L V S Y I S G E P I M A L R T F E E S P L Y A L 25498 ttcgatatgtttcgaaataatctgtttagatgtaaggtcgaacttatgctcacaatggtcacaattaaccttgaacgtctgggt 57 F D M F R N N L F R C K V E L M L T M V T I N L E R L G 25414 cgactccttcttcggttggttgttcagtttgttctttttctttgtcatcaacttcgtcttcttcactcgtttcatcttgaggct 85 R L L L R L V V Q F V L F L C H Q L R L L H S F H L E A 25330 cctcttgttcgtttaattcgtttgctaatacaggcaatgctccagctgagatttcgtcaagctgagcaagttcttccaaaatgc 113 P L V R L I R L L I Q A M L Q L R F R Q A E Q V L P K C 25246 gttcccattccttgtccgccttttccttcttactga 25211 141 V P I P C P P F P S Y* dplORF045 25340 atgaaacgagtgaagaagacgaagttgatgacaaagaaaaagaacaaactgaacaaccaaccgaagaaggagtcgacccagacg 1 M K R V K K T K L M T K K K N K L N N Q P K K E S T Q T 25424 ttcaaggttaattgtgaccattgtgagcataagttcgaccttacatctaaacagattatttcgaaacatatcgaaaagggcgta 29 F K V N C D H C E H K F D L T S K Q I I S K H I E K G V 25508 gagtggagattcttcgaatgtcctaagtgccattatcggttcaccacttatgtaggaaacaaggaaattgaaaaccttattcga 57 E W R F F E C P K C H Y R F T T Y V G N K E I E N L I R 25592 tttagaaatacttgtcgagctaaaatgaagcaggaacttcaaaaaggagctgctgctaatcaaaacacttaccattcatatcga 85 F R N-T C R A K M K Q E L Q K G A A A N Q N T Y H S Y R 25676 attcaggatgagcaagctgggcataaaatctcagggcttatggcgaagctaaagaaggagataaacattgaaaaacgagaaaaa 113 I Q D E Q A G H K I S G L M A K L K K E I N I E K R E K 25760 gaatgggtatctatatag 25777 141 E W V S I dplORF046 42774 atgccaatgtggctaaacgacacagcagtcttgacgacgattattacagcgtgcagcggagtgcttactgtcctactaaataag 1 M P M W L N D T A V L T T I I T A C S G V L T V L L N K 42858 ttattcgaatggaaatcgaataaagccaagagcgttttagaggatatctctacaactcttagcactcttaaacagcaggtcgac 29 L F E W K S N K A K S V L E D I S T T L S T L K Q Q V D 42942 gggattgaccaaacgacagtagcaatcaatcaccaaaatgacgtcattcaagacggaactagaaaaattcaacgttaccgtctt 57 G I D Q T T V A I N H Q N D V I Q D G T R K I Q R Y R L 43026 tatcacgacttaaaaagggaagtgataacaggctatacaactctcgaccattttagagagctctctattttattcgaaagttat 85 Y H D L K R E V I T G Y T T L D H F R E L S I L F E S Y 43110 aagaaccttggcggaaatggtgaagttgaagccttgtatgaaaaatacaagaaattaccaattagggaggaagatttagatgaa 113 K N L G G N G E V E A L Y E K Y K K L P I R E E D L D E 43194 actatctaa 43202 141 T I * dplORF047 47542 atgaaatttgaagatgaaaaacagttcatcgctgcaattgaagaagccggtgaattaaatgctaccaaaggcgacatggagaaa 1 M K F E D E K Q F I A A I E E A G E L N A T K G D M E K 47626 caagtcaaaagtcttcgtgatgctctaaaagagtacatgaaagaaaatgacattgaatctgctcaaggtaagcacttttctgct 29 Q V K S L R D A L K E Y M K E N D I E S A Q G K H F S A 47710 accttctacacgacagagcgctcaactatggacgaagaacgcttgaaagaaattatcgaaaaattagttgacgaagccgagacg 57 T F Y T T E R S T M D E E R L K E I I E K L V D E A E T 47794 gaagaaatgtgtgaaaaactttcagggcttatcgaatacaagcctgtcatcaatacgaaacttctcgaggatatgatttatcac 85 E E M C E K L S G L I E Y K P V I N T K L L E D M I Y H 47878 ggcgagattgaccaagaagcaattcttccagcagttgtcatttctgttacagaaggcattcgttttggaaaggctaaaatttag 47961 113 G E I D Q E A I L P A V V I S V T E G I R F G K A K I * dplORF048 16709 atggaaacaacactttatttcggttatcttacagcagattggaaagacggtcacaagaactacactttccactatgaaagcatt 1 M E T T L Y F G Y L T A D W K D G H K N Y T F H Y E S I 16625 cctgtaaaagaaactgagaaacaatataaggtcactggaatcaatcctaacttgtacttagacctaggctcagttattagaaag 29 P V K E T E K Q Y K V T G I N P N L Y L D L G S V I R K 16541 agcgaacttgacattgcagtattcaaagcatgtcctgtcgctgaaactggagtcacacttactcgcgacatggaagttgatgct 57 S E L D I A V F K A C P V A E T G V T L T R D M E V D A 16457 agaattgaaatcatcaagaaattaactacaagaatcgaacgccttaacgaaagaattaaagcaagaaatgaacaaggtaaacaa 85 R I E I I K K L T T R I E R L N E R I K A R N E Q G K Q 16373 gaaagccgccacctagtatctgcgctagaagattgcgctcgtcaaattgctggaatttatcaataa 16308 113 E S R H L V S A L E D C A R Q I A G I Y Q * dplORF049 44018 atgtttcaaccatttctcagcgagcatgtagccttggtcgtcaaagtagaaccaagacttgttttcttcgatatactcgaactc 1 M F Q P F L S E H V A L V V K V E P R L V F F D I L E L 43934 atcttttggataagttccgtttgctcgagcgtaccagaaaccagtagcatctttctgccagccaagtttcttctcagccggttg 29 I F W I S S V C S S V P E T S S I F L P A K F L L S R L 43850 agcatttgcgttagtcaagcgatagacgtagtagtaaggttgacctgcatagtaccaacgctcatcgtggtcgttgacggaaat 57 S I C V S Q A I D V V V R L T C I V P T L I V V V D G_N 43766 tccgtcgtaggcgtagttgcagtgaatgatgttatcactgtcaatgaacatccctgtatgacctccagcgcctgegctagcacc 85 S V V G V V A V N D V I T V N E H P C M T S S A-C A S T 43682 tttgcgtccccagatgaagatgtcgcctcgtttagcatcccacggagcattttcactaattag 43620 113 F A S P D E D V A S F S I P R S I F T N * dplORF050 15081 atgaacaatcagcgaaagcaaatgaacaaacgaatcgtcgaacttcgcgaagactatcaacgtgcaagaggtcgaataaacttc 1 M N N Q R K Q M N K R I V E L R E D Y Q R A R G R I N F WO 00/32825 PCT/IB99/02040 379 15165 cttcttgctgtaaaggaccacggcgaagaactcgaaaaccttgaagcctttgtgggatacattgacaatctagtcgaatgtttt 29 L L A V K D H G E E L E N L E A F V G Y I D N L V E C F 15249 cctgaaagccaacgaaatgtcttgaggctatgtgtattagatgaccttccagtcactaatgcggccgctgaaattggataccac 57 P E S Q R N V L R L C V L D D L P V T N A A A E I G Y H 15333 tatacatgggttcaccaacttcgagacaaagcagttgaaacacttgaagaaattttagatggggataacattattcgctctaaa 85 Y T W V H Q L R D K A V E T L E E I L D G D N I I R S K 15417 cacggaatcgaaattaaggagaaacttgatgaattatatggtaaaagtcattctagttag 15476 113 H G I E I K E K L D E L Y G K S H S S * dplORF051 29765 atgagttatgacgtgaattatgttaagaatcaagttcgtagagccattgaaaccgctcctactaaaatcaaggtacttcgaaac 1 M S Y D V N Y V K N Q V R R A I E T A P T K I K V L R N 29849 tcttgggtcagtgatggatatggaggaaagaaaaaggataaagcgaatgaagtcgtagcagacgaccttgtttgtttagttgat 29 S W V S D G Y G G K K K D K A N E V V A D D L V C L V D 29933 aattcaactgttcctgaccttttagccaattctactgacgcgggaaaaatttttgcccaaaatggagtgaaaattttcattcta 57 N S T V P D L L A N S T D A G K I F A Q N G V K I F I L 30017 tatgatgaaggcaaaatcattcaacgagccgatactatcgaaattaaaaactcaggaagacggtacagggtagtagaaacccac 85 Y D E G K I I Q R A D T I E I K N S G R R Y R V V E T H 30101 aatcttctcgagcaagacattttgatagaacttaaattggaggtgaacgactaa 30154 113 N L L E Q D I L I E L K L E V N D * dplORF052 30516 atgactaaacgaacgacaatgatggacagattgaaggaaattcttcctacatttcagctctcgcctgctcctatgcttccagga 1 M T K R T T M M D R L K E I L P T F Q L S P A P M L P G 30600 gttgaatttgacgagcaagatacagataggccggatgactacattgttcttcgatatagtcatagaatgcccagcgcaacaaat 29 V E F D E Q D T D R P D D Y I V L R Y S H R M P S A T N 30684 agcctaggaagttttgcttattggaaagttcaaatctacgtccattcaaactcaattattggtatcgacgaatatagcagaaag 57 S L G S F A Y W K V Q I Y V H S N S I I G I D E Y S R K 30768 gttcgaaacattatcaaggacatgggctacgaagtaacctatgcagaaactggtgactacttcgacacaatgctttctagatac 85 V R N I I K D M G Y E V T Y A E T G D Y F D T M L S R Y 30852 cgactagaaatcgaatatagaattccacaaggaggaaactaa 30893 113 R L E I E Y R I P Q G G N * dplORF053 50300 atgctaacattcgaaagaatagtatctatacgagcaccaacttgcatttcactcatttccccgctatatagaaggacatcatgc 1 M L T F E R I V S I R A P T C I S L I S P L Y R R T S C 50216 ccgttcttccaagcagttgcaagcattttatcaatagtccacgacttaccttgtccaggtcgagccattatgacaatcaaatcc 29 P F F Q A V A S I L S I V H D L P C P G R A I M T I K S 50132 tcaccaggaagtaagcctccaagcacgtcgtccaatagttcaaaccctgtcgatattccaagtctttcaccgtcatggtttcta 57 S P G S K P P S T S S N S S N P V D I P S L S P S W F L 50048 atagtattcgcccagtctagtcgaagtttagcatttcgagcaatgtctagtccgcctacgaatttagagcgattgaaaagttct 85 I V F A Q S S R S L A F R A M S S P P T N L E R L K S S 49964 tctagttttggaattatattcgcaatcgcaatgttactatctacttga 49917 113 S S F G I I F A I A M L L S T * dplORF054 14423 atgtgtgaaaattgtcaaaacgaaacattcaatactagaattttcaatgaagatgaaagtggctatgtcgacgcctcattcact 1 M C E N C Q N E T F N T R I F N E D E S G Y V D A S F T 14507 tacaaggagattcgcgacaccgcagcagctattagcaatcgagcggtagaaaagaaagaccgtgacagccttttagtcgctaca 29 Y K E I R D T A A A I S N R A V E K K D R D S L L V A T 14591 gttatggctcttcccgtttctcacgcagaagatttaggcaagagactttgtattgcaaattctcgattggaagcatttcgtgaa 57 V M A L P V S H A E D L G K R L C I A N S R L E A F R E 14675 gctgttcaagaggctctcgagaatgaaaaggctgaagatttaaaggacgttatcttaggtcttatcgacgttgacaaaaaaatt 85 A V Q E A L E N E K A E D L K D V I L G L I D V D K K I 14759 ggcaaccttgcattgcaattagttgaatcaggagcattataa 14800 113 G N L A L Q L V E S G A L * dplORF055 27627 atgcctaatgtgcgagttaagaaaactgattttaatcaaaccactcgaagcattgtcgcaattcctgaccactacgttgctttg 1 M P N V R V K K T D F N Q T T R S I V A I P D H Y V A L 27711 gctgctcaaattccagctaccgcagcaactcaagtagggaacaagaaatacattcttgccggaacttgcgtgaaaaatgctact 29 A A Q I P A T A A T Q V G N K K Y I L A G T C V K N A T 27795 acatttgaaggacgcaaaactggactcgaagtagtatctaccggtgaacaattcgacggagttatcttcgctgaccaagaagtg 57 T F E G R K T G L E V V S T G E Q F D G V I F A D Q E V 27879 tttgaaggtgaagaaaaagtaaccgtgacagtattagttcacggattcgtcaaatatgcagcccttcgaaaagttggcgatgct 85 F E G E E K V T V T V L V H G F V K Y A A L R K V G D A 27963 gtgcctgaatctaaaaacgcaatgattcttgtcgttaaatag 28004 113 V P E S K N A M I L V V K * dplORF056 19151 atggaaaataaatggaaagttatccattttcaaaactcatgtattaaacaagtagacgatgaaaaaaggaggctcctgttcgaa 1 M E N K W K V I H F Q N S C I K Q V D D E K R R L L F E 19067 gttccaggaactccttatcgtctacaagtttgggtgaaaatgagcttagttaaaattgaaacacgcgcaggaaatggctattat 29 V P G T P Y R L Q V W V K M S L V K I E T R A G N G Y Y 18983 aaaaggctagtatgccaagacgattttgtattttatggtaaggagtcaatagatggttacttaattgacgccacCataaCtggc 57 K R L V C Q D D F V F Y G K E S I D G Y L I D A T~I T G 18899 aaatctttggcggaatattgtgagcctatgaacaggcatattctcgaaactattgcatcgcgagaagcagctgaactgaacaga 85 K S L A E Y C E P M N R H I L E T I A S R E A A E L N R 18815 gctaaaaagcaagaccaacagaaatggagatactag 18780 113 A K K Q D Q Q K WRY * dplORF057 WO 00/32825 PCT/IB99/02040 380 9859 atgcaaaaatctctatttggacctaagctagtgcctgctagttcaaggcgcaagaaaagaacggttccaaaacctaaacctaaa 1 M Q K S L F G P K L V P A S S R R K K R T V P K P K P K 9943 atcgatgagcaagtggttgagcttatgaaccgcagagagcgtcaagtgcttgttcatagttgcatctattattattttaatgac 29 I D E Q V V E L M N R R E R Q V L V H S C I Y Y Y F N D 10027 tcaattatagcagacgggcagtatgacaaatggagccacgaactatattctcttatagtttcgcaccctgatgagtttcgacag 57 S I I A D G Q Y D K W S H E L Y S L I V S H P D E F R Q 10111 actgttctctataacgagtttaaacagtttgacggaaatactggaatgggtcttccatacgactgtcagtttgctgtaagggtc 85 T V L Y N E F K Q F D G N T G M G L P Y D C Q F A V R V 10195 gcagaaaggcttttaagaaaatga 10218 113 A E R L L R K * dplORF058 15633 atgacatcacgcgcatacaaaccaattcccacgcgcagagctagtgctaaacaagagaaggcagttgctaagcagttgggagga 1 M T S R A Y K P I P T R R A S A K Q E K A V A K Q L G G 15717 aaagtacagcctaattcaggagccactgactactacaaaggtgacgtcgtaacagactcaatgcttatagaatgcaagacagtt 29 K V Q P N S G A T D Y Y K G D V V T D S M L I E C K T V 15801 atgaagccacaaagttcagtcagcttgaaaaaggaatggttcctaaaaaatgaacaggaaaggttcgctcaaaaactcgactat 57 M K P Q S S V S L K K E W F L K N E Q E R F A Q K L D Y 15885 tctgctatcgctttcgactttggtgacggaggcgaacagtatatagcaatgtctataagtcagttcaagcgaatattagaggat 85 S A I A F D F G D G G E Q Y I A M S I S Q F K R I L E D 15969 agaaatgataaccttatttaa 15989 113 R N D N L I * dplORF059 30154 atgtctcagcctgaattagtatggaagcctgaagaatttgttagtaactgtgaacggtatcgaaacaagtttcaagtcgctgtc 1 M S Q P E L V W K P E E F V S N C E R Y R N K F Q V A V 30238 ataacagtctgcgaagtcgctgctactaagatggaagaatacgcaaagacgcatgctatttggacagaccgtacagggaatgct 29 I T V C E V A A T K M E E Y A K T H A I W T D R T G N A 30322 cgacagaaactcaaaggagaagctgcttgggtaagcgcagaccaaatcatgatagctgtatcacatcacatggactacgggttt 57 R Q K L K G E A A W V S A D Q I M I A V S H H M D Y G F 30406 tggctagaactagctcatggtcgaaaatacaaaattctcgaacaggctgtagaagacaatgtcgaagaactttttagagcgttg 85 W L E L A H G R K Y K I L E Q A V E D N V E E L F R A L 30490 agaaggttattagactag 30507 113 R R L L D * dplORF060 38070 gtgatagctgtatctgctatccctactccgctctttccaggtacaccgtcgactccatcacgcccaggagctcccggtaaacct 1 V I A V S A I P T P L F P G T P S T P S R P G A P G K P 37986 gcgtcacctttaggaccttctagtcgaatccatgtaaagtcgtcaggaactaattcgctcggtttcttattagtattaaggaca 29 A S P L G P S S R I H V K S S G T N S L G F L L V L R T 37902 ccaatgtatttcccagattctgcattaaaattagtccctaaaatgtcatctgcgtatctaataacaacttgggactcatttaca 57 P M Y F P D S A L K L V P K M S S A Y L I T T W D S F T 37818 gtttcccctgaaaggactccttcgccgtcctcatttagcaagtccatcaagtcttttcgagggtcttggaaaatgatagtagag 85 V S P E R T P S P S S F S K S I K S F R G S W K M I V E 37734 tttgaaaggtcgtcgtag 37717 113 F E R S S * dplORF061 19475 atggcgagaatgcaaagattatgcccgatgaaattttggaaggcggtaactaaaatgaaattcgaagtttattctgcgcgacta 1 M A R M Q R L C P M K F W K A V T K M K F E V Y S A R L 19391 tttgacgaagaggcgacatatgataggtatcgtgaagcactagagaaagttggaaatgtcgcttacttttgtgaaattgatact 29 F D E E A T Y D R Y R E A L E K V G N V A Y F C E I D T 19307 ggcaaccttgtaatcgaactcgagctagacagcctagatgacctaatcgcgctttcaaatgtagtgggaactggactaaaatta 57 G N L V I E L E L D S L D D L I A L S N V V G T G L K L 19223 tcacggccttatagagaagataagccttttcaattatggattgttgacgggtacatggaataa 19161 85 S R P Y R E D K P F Q L W I V D G Y M E * dplORF062 45284 gtgagaagcttcaatcaattccattgcggtgtcaatatcttcttccttgacgagtttaaaaattccgtcaatcgcccattcgta 1 V R S F N Q F H C G V N I F F L D E F K N S V N R P F V 45200 agatgcaggagcaatagatgcaagaagtttcttttggtcttctgtcaacccttttgcgcgaactccaatagaaacaccttttcg 29 R C R S N R C K K F L L V F C Q P F C A N S N R N T F S 45116 agtttcttcgatagtaacgaagttcttcttagagcgataggcgatgtaagactgagtgacgattcgagtagacgcaggaaaggc 57 S F F D S N E V L L R A I G D V R L S D D S S R R R K G 45032 ttcaacaattcgactttcaagagccttagtaatcgccatcacgctttcttttttaggagcaggttttcgaacagtagatttctc 85 F N N S T F K S L S N R H H A F F F R S R F S N S R F L 44948 actaactga 44940 113 T N * dplORF063 47200 atgaaattcactgaaggaaaaaattggtataaagttggagagatatgtcaaatgttgaaccgctctctatctacgattaatgtt 1 M K F T E G K N W Y K V G E I C Q M L N R S L S T I N V 47284 tggtatgaagcaaaagacttcgctgaagaaaataacattcacttcccgtttgttcttcctgaacctagaacagaccttgaccat 29 W Y E A K D F A E E N N I H F P F V L P E P R T D L D H 47368 cgtggttctcgattctgggatgacgaaggcgtgaacaaactcaaacgatttagggacaacctaatgcgcggtgattgcattc 57 R G S R F W D D E G V N K L K R F R D N L M R GD L A F 47452 tacactcgaactcttgtagggaaaactgaaagggaagcaattcaagaagatgctaaagcatttaaacgtgaacatggattggag 85 Y T R T L V G K T E R E A I Q E D A K A F K R E H G L E 47536 aattaa 47541 113 N * dplORF064 WO 00/32825 PCT/IB99/02040 381 29108 atggctacattgaaagctcttagcaccttaatcgtttccggagcagtagtgcattcagggtcggtattttcttgccctgaagcg 1 M A T L K A L S T L I V S G A V V H S G S V F S C P E A 29192 cttgcttcgtctttaattgaacgcaattttgegttcgagattaaggcggetgaagatggagaaacggtagaaactgttcctcaa 29 L A S S L I E R N F A F E I K A A E D G E T V E T V P Q 29276 acaattgaatcagttgaagaaattgacgaagttgaacaaatgcgcgaagagtatgcggctaaaaccgttcctgagctcgttgaa 57 T I E S V E E I D E V E Q M R E E Y A A K T V P E L V E 29360 ttagcaagagctaatggaattgacatttcttcaatttctcgaaaaagcgaatatatcgacgctttaattaagtacgaactagga 83 L A R A N G I D I S S I S R K S E Y I D A L I K Y E L G 29444 gagtaa 29449 113 E * dp1ORF065 51497 atgcagtttgtcataacctacatcaaacatctcgatgagctcgtccgtcaatttccgttcatacatataaggatgaataaaccg 1 M Q F V I T Y I K H L D E L V R Q F P F I H I R M N K P 51413 gtatttatcaagttcctcttcaggaatgattttatgCtcgactttttcagttctcccatttcttcgaaacgcttcagggctgac 29 V F I K F L F R N D F M L D F F S S P I S S K R F R A D 51329 gccttgcctaactacttcgctagatgttccaaaattccttttcagccactggtttccatagaaccctccatcgtttcgacctaa 5 1246 57 A L P N Y F A R C S K I P F Q P L V S I E P S I V S T * dplORF066 28898 gtgaccaactgcgtcaggtggaagcaataccactttaccgtcgtcaatcaagttgaactgacgaatgttaccaacgtcaggaag 1 V T N C V R W K Q Y H F T V V N Q V E L T N V T N V R K 28814 tttgtcagcgtcagcgaactgagcaattttcttagagtagacagcgatttgaagacctgttttttcagcgatgaatttctcagc 29 F V S V S E L S N F L R V D S D L K T C F F S D E F L S 28730 gtcacttgcaagaagcaagaagttttcccaagaaccttgaacaccaattgcaagagctttcttgatagagtcactcttagtcat 57 V T C K K Q E V F P R T L N T N C K S F L D R V T L S H 28646 ttggttataagtgtttcggttcaagaccattcgagtagggcgaacacctgtacgattttcgatgtcatccattgctgctaa 28566 85 L V I S V S V Q D H S S R A N T C T I F D V I H C C * dplORF067 45061 gtgacgattcgagtagacgcaggaaaggcttcaacaattcgactttcaagagccttagtaatcgccatcacgctttctttttta 1 V T I R V D A G K A S T I R L S R A L V I A I T L S F L 44977 ggagcaggttttcgaacagtagatttctcactaactgaaccaacttcttccggctgttccttaacttcaggaatttcttcctca 29 G A G F R T V D F S L T E P T S S G C S L T S G I S S S 44893 aggacttcttttttaggtttgggaacgactctaccttttcgagcaggtcgagcaactgcaggagcagcctttttagcaggttta 57 R T S F L G L G T T L P F R A G R A T A G A A F L A G L 44809 gcagcttcttcttttttaggttcagtttcatcttccattgtgtaccaacgttegagagttgaagctgaaaggtga 44735 85 A A S S F L G S V S S S I V Y Q R S R V E A E R* dplORF068 29451 atggcagctcaaacggacattgaattagtcaaaatcaatatcgataacgataattctccgtcaccaatgactgaccaaagtatc 1 M A A Q T D I E L V K I N I D N D N S P S P M T. D Q S I 29535 tcagctcttttagacaagcataaatctgtcgcctatgttagttatatgatttgcttaatgaagacccggaatgacgtggtaacc 29 S A L L D K H K S V A Y V S Y M I C L M K T R N D V V T 29619 cttggacctatcagtctaaaaggtgacgcagactactggaaacaaatggcgcaattctattatgaccaatataagcaagaacag 57 L G P I S L K G D A D Y W K Q M A Q F Y Y D Q Y K Q E Q 29703 cttgaaactgatgaaaagtcgaacgctggttcgacaatcttaatgaaaagggctgatgggacatga 29768 85 L E T D E K S N A G S T I L M K R A D G T * dplORF069 20411 atgaaactttatcacgccactgattttgataatcttggtaaaattctagctgaaggattgaagccttcagctggagttatttac 1 M K L Y H A T D F D N L G K I L A E G L K P S A G V I Y 20327 ctagcagaaagttatgaaaaggctctagcctttttatcgcttegaaatgttgatactattgtcgttctcgaacttgaagtagat 29 L A E S Y E K A L A F L S L R N V D T I V V L E L E V D 20243 attgaaaaatgtactgaaagtttcgaccataatgaaaagatgttttgtagcctatttcatttcgacacttgtcgcgcttggact 57 I E K C T E S F D H N E K M F C S L F H F D T C R A W T 20159 tatgacaagacaattgaagtagacgacattgacttttcgaaagctcgaaaatatgatagaaagtga 20094 85 Y D K T I E V D D I D F S K A R K Y D R K * dplORF070 15973 atgataaccttatttaaaataaacagtgaaggaacagttactccaattaaagggtcagccatgcaactgtacgcagaccttatt 1 M I T L F K I N S E G T V T P I K G S A M Q L Y A D L I 16057 cctatacaagaggacgatatacagttcgttgatataactggacttgaccctattgttcgagaaaacgtacttgagctcatttca 29 P I Q E D D I Q F V D I T G L D P I V R E N V L E L I S 16141 cggagccgtgtaggagtttcaaaatatggtacaaacctcgaccagaatgatgtcgacgatttcctacagcacgccaaagaagaa 57 R S R V G V S K Y G T N L D Q N D V D D F L Q H A K E E 16225 gcgctcgactttgctaactacctaaccaagctacaaagtcaacaaaagcaaaataaatag 16284 85 A L D F A N Y L T K L Q S Q Q K Q N K * dplORF071 38904 gtgaaacaggtcctagaggagttcaaggtcttcaaggtcctcaagggcttcaaggaattcctggacctgcaggagctgacggac 1 V K Q V L E E F K V F K V L K G F K E F L D L Q E L T D 38988 gttcgcaatatactcacctcgctttctctaatagtccaaacggtgagggatttagtcatactgacagcggacgagcatacgtcg 29 V R N I L T S L S L I V Q T V R D L V I L T A D -:H- T S 39072 gtcagtatcaagatttcaatcccgtccattcaaaagaccctgcagcctatacatggacgaaatggaaggggaatgacggagctc 57 V S I K I S I P S I Q K T L Q P I H G R N G R G M T E L 39156 aagggatacccgggaagccaggcgcagacggtaagactaattatttccatatag 39209 85 K G Y P G S Q A Q T V R L I I S I * dplORF072 51045 atgttccttcgtcttcaagttgtctcgaaagtttttcaattatttgttcaggagtcgcttcaatttgaagaccatttactttca WO 00/32825 PCT/IB99/02040 382 1 M F L R L Q V V S K V F Q L F V Q E S L Q F E D H L L S 50961 tcaaaatgcttcaactccttcccttgtaaccttacttcgaagacgagcagtcgacctagaggcttttgctttcaatggagagct 29 S K C F N S F P C N L T S K T S S R P R G F C F Q W R A 50877 ttcgcctttttcagttccttcttcgccttcctctttgaatcctataagagtataggttccagtttcaacgtcccacatatattc 57 F A F F S S F F A F L F E S Y K S I G S S F N V P H I F 50793 gatgatttttcggtcttcgccatatcggtttttaacgacagatag 50749 85 D D F S V F A I S V F N D R * dplORF073 14262 gtgaacgcttgccggaagaatacgacgaagaaacttgggaacctatcactgaagcagaatacatcaagcgaacagaaaaaccta 1 V N A C R K N T T K K L G N L S L K Q N T S S E Q K N L 14346 aagcagttgcaaaacctactcgaaaaactccagcgccttctcgtcgccctcgcccttaaaagaaaggttgaaataaaatgtgtg 29 K Q L Q N L L E K L Q R L L V A L A L K R K V E I K C V 14430 aaaattgtcaaaacgaaacattcaatactagaattttcaatgaagatgaaagtggctatgtcgacgcctcattcacttacaagg 57 K I V K T K H S I L E F S M K M K V A M S T P H S L T R 14514 agattcgcgacaccgcagcagctattagcaatcgagcggtag 14555 85 R F A T P Q Q L L A I ER * dplORF074 32298 gtgacgaaaagaaaaatccaggattgcaaatgcttatggagtgactattttcagtcgctcctctttttgtatatagaaaggaaa 1 V T K R K I Q D C K C L W S D Y F Q S L L F L Y I E R K 32382 ttacatggattttgggtcaattgcagcaaaaatgactttggatatctcaaacttcacaagtcaattaaatcttgctcaaagtca 29 L H G F W V N C S K N D F G Y L K L H K S I K S C S K S 32466 agcgcaacggctcgcactagagtcttcgaagtcctttcaaattggttctgctttaacaggattagggaaaggacttacgactgc 57 S A T A R T R V F E V L S N W F C F N R I R E R T Y D C 32550 ggttacccttcctcttatgggatttgcagccgcctctattaa 32591 85 G Y P S S Y G I C S R L Y * dplORF075 22447 atggcaaagttttgtccgttgaattccgtcatggcccaaagggaaaatgaaagagccatcgatactgtttttcctgaacgaatg 1 M A K F C P L N S V M A Q R E N E R A I D T V F P E R M 22363 gaaccgtctgctatgacgatatcgaaagttcgaaaaggtgagccctttgtccaccatgttaggagctggagttgtttcttacta 29 E P S A M T I S K V R K G E P F V H H V R S W S C F L L 22279 aaagggacgaagttgaacttaggtagtttatttctcaggcttattgtcattatcagtcactcctttaatgtaggaacctgttgc 57 K G T K L N L G S L F L R L I V I I S H S F N V G T C C 22195 gtcactaaattcttgccaaacggcttgagctgctttatctag 22154 85 V T K F L P N G L S C F I * dplORF076 5728 gtgagagcattttcttcactcacgtcttcgagcaagtggtcgaatgtagggtactcttcatcttctgtaacaatatcaatattg 1 V R A F S S L T S S S K W S N V G Y S S S V T I S I L 5644 tactcaccattcccaataacttttagcgaagattcttcaggaactaatgtgacggttgcggccgtggtcttttctacaagtttt 29 Y S P F P I T F S E D S S G T N V T V A A V V F S T S F 5560 ccaaactgctctgctttcacaatcacgtcaatttcaacatcgctgtcgataatgcatcgaaggaagtttgagccatcatacgct 57 P N C S A F T I T S I S T S L S I M H R R K F E P S Y A 5476 gtaaacatgacgcattcgccgtcaccaaaaatatgccaatag 5435 85 V N M T H S P S P K I C Q * dplORF077 14800 atggaacgaataaagacgctatttcacgtgatttatgctaacggcactcatttagaagtagcagctttgttcgataccgttgat 1 M E R I K T L F H V I Y A N G T H L E V A A L F D T V D 14884 gattatgatgacgttatagaggacatccaggggtatattgatacccctgacctttataatcaaaggagcattagaatggcgcct 29 D Y D D V I E D I Q G Y I D T P D L Y N Q R S I R M A P 14968 tacaatcctgacatcaatggtgacgctattgctactgacattttactacgactagatgatattatctacgtcgacgcaacttgt 57 Y N P D I N G D A I A T D I L L R L D D I I Y V D A T C 15052 gaaactattaaatacgaggagcctattgcatga 15084 85 E T I K Y E E P I A dplORF078 17507 atggcaacagtaaaggaaacagtaaaatttgacggacgtcttgtaactatcttcgactacgacgatttagagtgggaaggatat 1 M A T V K E T V K F D G R L V T I F D Y D D L E W E G Y 17423 gcacctaatgaaggattcgaagatgttgaggacatggaagtccttagcattcgagttcgaaacgaaggtgaggacgacgagtgg 29 A P N E G F E D V E D M E V L S I R V R N E G E D D E W 17339 gttgaagttatcgcctgctatgaaaacgatgacgaggacgaagatttggaagggttataa 17280 57 V E V I A C Y E N D D E D E D L E G L * dplORF079 35288 atggaactgataccattgataaatcctcgaacaaggttgacccctgcgcttaccatttgtccagcgaatccagtaaccttagaa 1 M E L I P L I N P R T R L T P A L T I C P A N P V T L E 35204 acaattgaagttcccatgctgccaattttagagacagctgaaccaatcattgacccaataccactaatgaagtttcgaatcagg 29 T I E V P M L P I L E T A E P I I D P I P L M K F R I R 35120 ttcgcacctcctgaaaccatctgtcccacaaagctagcaatcttgctaactaatgatgaaagcatgtttccagctgtcgataaa 57 F A P P E T I C P T K L A I L L T N D E S M F P A V D K 35036 agtgagccgagaagtgaagcaataccttga 35007 85 S E P R S E A I P * dplORFO8O 42490 atgttgaaccttacaaaatcgcgccaaattgtggcagagttcactattggacaaggagctgaaaagaaact tgtaaacaacg 1 M L N L T K S R Q I V A E F T I G Q G A E K K L-V K T T 42574 attgtgaacattgatgcaaacgcagtatcaaccgtctctgaaactcttcatgacccagacttgtatgctgcgaaccgtcgagaa 29 I V N I D A N A V S T V S E T L H D P D L Y A A N R R E 42658 cttcgagctgacgagcaaaaacttcgcgaaactcgttacgcaatcgaagatgaaattctagctgaacagtcaaagactgaaaca 57 L R A D E Q K L R E T R Y A I E D E I L A E Q S K T E T 42742 gctctaacagctgaataa 42759 WO 00/32825 PCT/IB99/02040 383 85 A L T A E * dplORF081 55466 atgttcaggaacagtatcgtccatctgttggtctgcgtcaaagttaaaggggtcgaaatcttcgttcttgctagcgtcgatata 1 M F R N S I V H L L V C V K V K G V E I F V L A S V D I 55382 ctcgaactcgtattcaggaagactcatatcaggaagccttcttcttcgaccggtagctgtttgaacatatcccaagtcctgcgc 29 L E L V F R K T H I R K P S S S T G S C L N I S Q V L R 55298 ctgctgttgaacgaatatgatatagtctgccactttagggaactcggtgaagaaatcttcaataaccttattcgcttctttgac 57 L L L N E Y D I V C H F R E L G E E I F N N L I R F F D 55214 agatacattcatctgctcagcgattga 55188 85 R Y I H L L S D * dplORF082 44728 gtgaacttcacctttcagcttcaactctcgaacgttggtacacaatggaagatgaaactgaacctaaaaaagaagaagctgcta 1 V N F T F Q L Q L S N V G T Q W K M K L N L K K K K L L 44812 aacctgctaaaaaggctgctcctgcagttgctcgacctgctcgaaaaggtagagtcgttcccaaacctaaaaaagaagtccttg 29 N L L K R L L L Q L L D L L E K V E S F P N L K K K S L 44896 aggaagaaattcctgaagttaaggaacagccggaagaagttggttcagttagtgagaaatctactgttcgaaaacctgctccta 57 R K K F L K L R N S R K K L V Q L V R N L L F E N L L L 44980 aaaaagaaagcgtga 44994 85 K K K A * dplORF083 35974 atgccttcagggtttttaaatcctgagtccttaaatcctgcgaaagtgagtcctacatattctagcacggttgcacctttgtcg 1 M P S G F L N P E S L N P A K V S P T Y S S T V A P L S 35890 acaaggtcaattccgtcgaccaatagcgtctgtctgctagccatctatttctcctttacggtgttacaatgttaccaaaccctg 29 T R S I P S T N S V C L L A I Y F S F T V L Q C Y Q T L 35806 atagagtttctttacttctattatacaatcctctcgacagtttgtcaacgtcgtcattgtttcgaactacgattgttccaatgt 57 I E F L Y F Y Y T I L S T V C Q R R H C F E L R L F Q C 35722 tga 35720 85 * dplORF084 15445 atgaattatatggtaaaagtcattctagttagtgtctttgtactgtcagccttttgcatgacttgctcaatggtttatttggtt 1 M N Y M V K V I L V S V F V L S A F C M T C S M V Y L V 15529 acaggtaagcaagaggaccaccgtagtaccgtcgcccttgtatttggcgctctcgtaagctctgcggcgttctattcgacactc 29 T G K Q E D H R S T V A L V F G A L V S S A A F Y S T L 15613 tttatcctcgcctatctgccatga 15636 57 F I L A Y L P * dplORF085 10847 gtgatgactataatcaaggactttttcgagccttgtgatactgtcacgcattcctccatttgcaagtttcccaataaacgaaag 1 V M T I I K D F F E P C D T V T H S S I C K F P N K R K 10763 ggcgtcacgctcataactataaccagctccttcttcattttcactttcgataataaattgaagttgattaacgatgtcgtcatt 29 G V T L I T I T S S F F I F T F D N K L K L I N D V V I 10679 atcaattcgagtaaagtcaaaccgttgaactcgactgagaatagtgtcaggaatcttttgagggtcagtagtacatag 10602 57 I N S S K V K P L N S T E N S V R N L L R V S S T * dplORF086 52760 atatgggaaaagtatcaattcaaaaatcaggaacatttagctcagggtctaataacgagtttttcacactcgctgaccacggtg 1 1 W E K Y Q F K N Q E H L A Q G L I T S F S H S L T T V 52844 acagcgcaattgtcactctattgtatgatgacccggaaggcgaagacatggattatttcgtag 52906 29 T A Q L S L Y C M M T R K A K T W I I S * dplORF087 30036 atgattttgccttcatcatatagaatgaaaattttcactccattttgggcaaaaatttttcccgcgtcagtagaattggctaaa 1 M I L P S S Y R M K I F T P F W A K I F P A S V E L A K 29952 aggtcaggaacagttgaattatcaactaaacaaacaaggtcgtctgctacgacttcattcgctttatcctttttctttcctcca 29 R S G T V E L S T K Q T R S S A T T S F A L S F F F P P 29868 tatccatcactgacccaagagtttcgaagtaccttgattttagtaggagcggtttcaatggctctacgaacttga 29794 57 Y P S L T Q E F R S T L I L V G A V S M A L R T * dplORF088 5040 atgaaaaaagttcaaacttatcaagaatatctaaaactagttgagttcaaacgtcaactttctttaaatcttcgagaaggaaaa 1 M K K V Q T Y Q E Y L K L V E F K R Q L S L N L R E G K 5124 ataggagtcgatgaagcggttattcaattattcaccttctatagtttcaacaatatcgaggaacctcctttcattgtactcaaa 29 I G V D E A V I Q L F T F Y S F N N I E E P P F I V L K 5208 atgcaagaggetgccgtgaacgggacttatgaagcaaaactcaatatgcttaaaagatttaaaattatttag 5279 57 M Q E A A V N G T Y E A K L N M L K R F K I I * dplORF089 12495 atgtcaatcatgtcgctatcaatagtcgagtatttagacacaaaatgccttttcaactgcgcgtcagtcattttctcaaactca 1 M S I M S L S I V E Y L D T K C L F N C A S V I F S N S 12411 acacaattatcaggaaaggcctttagcaacttgcttcgcttgtcaattttagtaaccatcaaaacaagtgtcccatatctaaca 29 T Q L S G K A F S N L L R L S I L V T I K T S V P Y L T 12327 tccggaagccttttccacctcgactcattagacagaaactccttatcatctcgaacagcgaatattcgatga 12256 57 S G S L F H L D S L D R N S L S S R T A N I R * dplORF090 27037 atgctaaaattttcattgacggcgacggtcaacattttgtacctcacgcacgtttcgatgaagttgttcaaragcgcgatgcag 1 M L K F S L T A T V N I L Y L T H V S M K L F N S A M Q 27121 ctaacggctcaattaattcttataaagaacaagtcgcgacgctttctaaacaggtcaaagataacggtgatgcgcagaccacta 29 L T A Q L I L I K N K S R R F L N R S K I T V M R R P L 27205 tccaaaaccttcaagagcaactcgacaagcagtctcaacttgcaaaaggcgctgtga 27261 57 5 K T F K S N S T S S L N L Q K A L * WO 00/32825 PCT/IB99/02040 384 dplORF091 43189 atgaaactatctaacgaacaatatgacgtagcaaagaacgtggtaaccgtagtcgttccagcagcgattgcactaattacaggt 1 M K L S N E Q Y D V A K N V V T V V V P A A I A L I T G 43273 cttggagcgttgtatcaatttgacactactgctatcacaggaaccattgcacttcttgcaacttttgcaggtactgttctagga 29 L G A L Y Q F D T T A I T G T I A L L A T F A G T V L G 43357 gtttctagccgaaactaccaaaaggaacaagaagctcaaaacaatgaggtggaataa 43413 57 V S S R N Y Q K E Q E A Q N N E V E * dplORF092 46989 atgaaaactatctccatattaaggaaagacactaaaaggaagccggacaggaacggaagaaaaactgcactcgaactagctcaa 1 M K T I S I L R K D T K R K P D R N G R K T A L E L A Q 47073 gagattgatatgtcacctagtgagttagcagagctccttcaaattcctgaaaggacggcaaccagaattttaaaactcgacaaa 29 E I D M S P S E L A E L L Q I P E R T A T R I L K L D K 47157 ctgctcaacaaagagcaatgctcaataatagaaaggtatataaatgaaattcactga 47213 57 L L N K E Q C S I I E R Y I N E I H * dplORF093 45756 atgcaacatacgattaaacaatgtttgaaacttgccttcctgctaactgcaatatcaattgcctgtttagttttccctaaacct 1 M Q H T I K Q C L K L A F L L T A I S I A C L V F P K P 45672 tgctcatcgcctaaaaggaaacatggatgctcttgtgcgtattcgaaacattcaacctggtgcgcgaatggagtagtcttgaac 29 C S S P K R K H G C S C A Y S K H S T W C A N G V V L N 45588 gaaaactgctcattgcttgaagaagctattcggtttcgagagtcaatgtag 45538 57 E N C S L L E E A I R F R E S M * dplORF094 8281 atgtacgaattagttctatcactaaaattgacgccgacagcgccgatgtctcaagatgtcgaaaagtgcttcaaaaggctcaag 1 M Y E L V L S L K L T P T A P M S Q D V E K C F K R L K 8365 tatattcagtggcggcaggtgaatgcattaaaattgcacacggatttgctcttgaacttcctaagggatatgaagcaatcttgc 29 Y I Q W R Q V N A L K L H T D L L L N F L R D M K Q S C 8449 atcctcgttccagtctttttaagaaaactggtctaa 8484 57 I L V P V F L R K LV * dplORF095 8877 gtgggaaaactacttcagctctcgacattgtcaagaatgcgcaaatggtatttgagcaggaatgggaacagaagactgaagaac 1 V G K L L Q L S T L S R M R K W Y L S R N G N R R L K N 8961 tcaaggaaaagctggaaaatgcgcgtgcatccaaagctagcaagactgctgtcaaggaacttgaaatgcaactcgatagtcttc 29 S R K S W K M R V H P K L A R L L S R N L K C N S I V F 9045 aagagcctcttaagattgtatatcttgaccttgagaatacattag 9089 57 K S L L R L Y I L T L R I H * dplORF096 46681 gtgattcataaattcttcaatttcgttgaacttatctgcggtttctcctgttaccaggttgcatttgactgtcttcgaaagtat 1 V I H K F F N F V E L I C G F S C Y Q V A F D C L R K Y 46597 cttagcaagaggttcaataaccttttcccaattgctaaatatcacgcaggactttccttgctggatacattcctcgacaatttc 29 L S K R F N N L F P I A K Y H A G L S L L D T F L D N F 46513 gatacatctttcgaacttgcaagacttgacatcttgagtagttaa 46469 57 D T S F E L A R L D I L S S * dplORF097 39100 atggacgggattgaaatcttgatactgaccgacgtatgctcgtccgctgtcagtatgactaaatccctcaccgtttggactatt 1 M D G I E I L I L T D V C S S A V S M T K S L T V W T I 39016 agagaaagcgaggtgagtatattgcgaacgtccgtcagctcctgcaggtccaggaattccttgaagcccttgaggaccttgaag 29 R E S E V S I L R T S V S S C R S R N S L K P L R T L K 38932 accttgaactcctctaggacctgtttcacctatcttggaaactga 38888 57 T L N S S R T C F T Y L G N * dplORF098 43627 gtgaaaatgctccgtgggatgctaaacgaggcgacatcttcatctggggacgcaaaggtgctagcgcaggcgctggaggtcata 1 V K M L R G M L N E A T S S S G D A K V L A Q A L E V I 43711 cagggatgttcattgacagtgataacatcattcactgcaactacgcctacgacggaatttccgtcaacgaccacgatgagcgtt 29 Q G C S L T V I T S F T A T T P T T E F P S T T T M S V 43795 ggtactatgcaggtcaaccttactactacgtctatcgcttga 43836 57 G T M Q V N L T T T S I A * dplORF099 38298 atgcaagttcgccatctgctactgaagctccagctggtggatggtctacgcaagttcctaccgtcccaggtggtcagtatttat 1 M Q V R H L L L K L Q L V D G L R K F L P S Q V V S I Y 38382 ggactcgaacaagatggcgctacactgaccaaactgatgaaattggatattcagtttcaagaatgggcgagcagggtcctaaag 29 G L E Q D G A T L T K L M K L D I Q F Q E W A S R V L K 38466 gtgacgcaggtcgtgacggtattgcaggaaagaacggaatag 38507 57 V T Q V V T V L Q E R T E * dplORF100 1597 atgcagttgacaccaagcgagttctatttggatttagaactacggctgagaatatgtcaagattccttacctggactctcacgg 1 M Q L T P S E F Y L D L E L R L R I C Q D S L P G L S R 1681 agcttatgtggaagcatgctcgtatcgactctatcaaactatgggaaactcctacaggttgcgcagaatgtacttactacgaga 29 S L C G S M L V S T L S N Y G K L L Q V A Q N V L T T R 1765 ttttcacagaagacgagattgaaatgttcaagaacgtaa 1803 - 57 F S Q K T R L K C S R T * dplORF101 19220 gtgataattttagtccagttcccactacatttgaaagcgcgattaggtcatctaggctgtctagctcgagttcgattacaaggt 1 V I I L V Q F P L H L K A R L G H L G C L A R V R L Q G 19304 tgccagtatcaatttcacaaaagtaagcgacatttccaactttctctagtgcttcacgatacctatcatatgtcgcctcttcgt 29 C Q Y Q F H K S K R H F Q L S L V L H D T Y H M S P L R WO 00/32825 PCT/IB99/02040 385 19388 caaatagtcgcgcagaataaacttcgaatttcattttag 19426 57 Q I V A Q N K L R I S F * dplORF102 4034 atgataacgtgggaatgtttgactgtatcgccgaactcgataaaattcctggtgtatttagacagcctaagacacgtgaacagc 1 M I T W E C L T V S P N S I K F L V Y L D S L R H V N S 4118 ttttggaagcaccacaaatttcttgggataattatctatacatgcgcgagcgaatggttgagaaagacaagctcttacctattt 29 F W K H H K F L G I I I Y T C A S E W L R K T S S Y L F 4202 tccatatgggagaagactttaaatggctcaacttga 4237 57 S I W E K T L N G ST * dplORF103 49352 ttgaatcatagatatagtaacatcacaactatttttctttggcagattgtctttctttgtatttgctgcgcggtgtcctattgt 1 L N H R Y S N I T T I F L W Q I V F L C I C C A V S Y C 49436 gcaggagtgcataatgagcgagagtctcaagataaggtgattcaaagttataagcagaaagaaaagtcagccgtctacttgaca 29 A G V H N E R E S Q D K V I Q S Y K Q K E K S A V Y L T 49520 gtcgatagttcaggagettggctaggaagtgctccgggagccaaggaaagtcctctctacaatgaaaagggacagcatgtagga 57 V D S S G A W L G S A P G A K E S P L Y N E K G Q H V G 49604 aaattgaaagaggtgggagagtga 49627 85 K L K E V G E * dplORF104 21427 atgagaaaaagagtgattttgaagctaaaaaggttgaactggtatgtccttaattcctactctcgaatggttgagtttttcgaa 1 M R K R V I L K L K R L N W Y V L N S Y S R M V E F F E 21343 cttttgaacttttcgaatggttcgacttttcgaaggattgaggttttcgaaccggttgagtttttcgagcattctcgacttttc 29 L L N F S N G S T F R R I E V F E P V E F F E H S R L F 21259 gacccctttctatgctcgacttttCgagtgttttga 21224 57 D P F L C S T F R V F * dplORF1O5 2028 atgatagtcgcatccaccagttcgaatgaaaatagtcttttgacctataaccattccttcaccttgaattgtaggaccgaaaat 1 M I V A S T S S N E N S L L T Y N H S F T L N C R T E N 1944 ttccatgataggcattttctcagggtcgcgaacattgattcgaatcttgcctctttcaggctgattgtattgattaaccattat 29 F H D R H F L R V A N I D S N L A S F R L I V L I N H Y 1860 cctgctcctgctctaaaatttcgcggacagtaa 1828 57 P A P A L K F R G Q * dplORF106 10529 atgaacctcgtcaatgatgtaaactttgaactcgctgtccatagacttgtatctagaatcttcaataatgtttcgaacattttc 1 M N L V N D V N F E L A V H R L V S R I F N N V S N I F 10445 taccccattattagaagcagcatcaatttcaataggagagccaagtcctttgttcacatccttcgcgaaaattcgagcagtagt 29 Y P I I R S S I N F N R R A K S F V H I L R E N S S S S 10361 ggttttaccagttccagcgccaccacagaatag 10329 57 G F T S S S A T T E * dplORF107 10750 atgagcgtgacgccctttcgtttattgggaaacttgcaaatggaggaatgcgtgacagtatcacaaggctcgaaaaagtccttg 1 M S V T P F R L L G N L Q M E E C V T V S Q G S K K S L 10834 attatagtcatcacgttgacatggaagccgtttctaatgcactag 10878 29 I I V I T L T W K P F L M H * dplORF108 49447 atgcactcctgcacaataggacaccgcgcagcaaatacaaagaaagacaatctgccaaagaaaaatagttgtgatgttactata 1 M H S C T I G H R A A N T K K D N L P K K N S C D V T I 49363 tctatgattcaatttcgcttacctccaatcctcttacattgcttgcctgaaaatctagaaccactgaagtatcatatatacgac 29 S M I Q F R L P P I L L H C L P E N L E P L K Y H I Y D 49279 tataaagcctttggcctaaaaggtcaataa 49250 57 Y K A F G L K G Q * dplORF109 31632 atgtggttgtcgaagtcccaaatagttgattctccttcaactttccagcctttgaaagccttacctgttaaggtagggtcaact 1 M W L S K S Q I V D S P S T F Q P L K A L P V K V G S T 31548 ggttttggagaaatcttcttacctgcttcaactcgaactgcgtcggcggttcctgttccaccgttcaaatcgaatgtcacgcga 29 G F G E I F L P A S T R T A S A V P V P P F K S N V T R 31464 cgaagaaccgctggaagttgtgccacatag 31435 57 R R T A G S C A T * dplORF110 16444 atgatttcaattctagcatcaacttccatgtcgcgagtaagtgtgactccagtttcagcgacaggacatgctttgaatactgca 1 M I S I L A S T S M S R V S V T P V S A T G H A L N T A 16528 atgtcaagttegctctttctaataactgagcctaggtctaagtacaagttaggattgattccagtgaccttatattgtttctca 29 M S S S L F L I T E P R S K Y K L G L I P V T L Y C F S 16612 gtttcttttacaggaatgctttcatag 16638 57 V S F T G M L S * dplORFIll 28657 gtgactctatcaagaaagctcttgcaattggtgttcaaggttcttgggaaaacttcttgcttcttgcaagtgacgctgagaaat 1 V T L S R K L L Q L V F K V L G K T S C F L Q V T L R N 28741 teategetgaaaaaacaggtettcaaategatgtctactctaagaaaatt gtcagttagetgacgetgacaaactteetgacg 29 S S L K K Q V F K S L S T L R K L L S S L T L T N-F--L T 28825 ttggtaacattcgtcagttcaacttga 28851 57 L V T F V S S T * dplORF112 32207 atgcaaactgatttaggcaaatactgcttcgacgcagcagccgttgcttatattagatatttgcaggaagacaagactcctagg 1 M Q T D L G K Y C F D A A A V A Y I R Y L Q E D K T P R 32291 tatcctggtgacgaaaagaaaaatccaggattgcaaatgcttatggagtga 32341 WO 00/32825 PCT/IB99/02040 386 29 Y P G D E K K N P G L Q M L M E dplORF113 17715 atgaaaacagttaaagaagcaatcaaacaattcggtgatgaatggtggtacgaaattatcaacgaaaacggccaaatgattcaa 1 M K T V K E A I K Q F G D E W W Y E I I N E N G Q M I Q 17631 gacggaagaatcgaagacatgggcgaatacatggaagaaacggtcgaccaagttaagttcatcaactatggtgacatcgaatct 29 D G R I E D M G E Y M E E T V D Q V K F I N Y G D I E S 17547 caaattatcaaactatatatcgcataa 17521 57 Q I I K L Y I A * dplORF114 52952 atgctattggcgaagacggggaaacagtccatcctgataattgtccattatgccaaaacggattccctcgtattgaaaaactat 1 M L L A K T G K Q S I L I I V H Y A K T D S L V L K N Y 53036 ttcttcaactttacaaccatgatacgggaaaagttgaaacatgggaccgaggccgttcttatgttcaaaagattgttacattta 29 F F N F T T M I R E K L K H G T E A V L M F K R L L H L 53120 tcaataaatatggaagccttgtga 53143 57 S I N M E A L * dplORF115 5342 atgagcctcctttttttgatatatataatatacacgaattatcgcgagtttgtaaagccgtttctaaataattttaaatctttt 1 M S L L F L I Y I I Y T N Y R E F V K P F L N N F K S F 5258 aagcatattgagttttgcttcataagtcccgttcacggcagcctcttgcattttgagtacaatgaaaggaggttcctcgatatt 29 K H I E F C F I S P V H G S L L H F E Y N E R R F L D I 5174 gttgaaactatagaaggtgaataa 5151 57 V E T I E G E * dplORF116 20662 atgaaattttcaaactttgctaaagcacttactaatgaatacctaatggtagtgaacaatgaccaagctgaagtcttaggcgca 1 M K F S N F A K A L T N E Y L M V V N N D Q A E V L G A 20578 ggaaatatcgaaaacattctcaacggttcgaactttgctaatgttgtagctgaagcgacagttttaaaactcgaaaaactcagc 29 G N I E N I L N G S N F A N V V A E A T V L K L E K L S 20494 gaagaggaagctattgagtag 20474 57 E E E A I E * dplORF117 24680 atgataacaggctgctcgaacattttaaatcgaagtgaatctcgtaagtcactaatagttttgttcaagttatctgctactgtg 1 M I T G C S N I L N R S E S R K S L I V L F K L S A T V 24596 ataaggtctttgacatcgcttgtcccgtatatgtcattagtcaatggttcattaagaataactcgacaaggaatttgcttcaag 29 I R S L T S L V P Y M S L V N G S L R I T R Q G I C F K 24512 ccggttggggcggattcttga 24492 57 P V G A D S * dplORF118 15023 atgatattatctacgtcgacgcaacttgtgaaactattaaatacgaggagcctattgcatgaacaatcagcgaaagcaaatgaa 1 M I L S T S T Q L V K L L N T R S L L H E Q S A K A N E 15107 caaacgaatcgtcgaacttcgcgaagactatcaacgtgcaagaggtcgaataaacttccttcttgctgtaaaggaccacggcga 29 Q T N R R T S R R L S T C K R S N K L P S C C K G P R R 15191 agaactcgaaaaccttga 15208 57 R T R K P * dplORF119 41054 atggaggttcaacatccccgattcagtacgtcctactttttcgggcatttctttagtagacacgacttcagcggttcgacagat 1 M E V Q H P R F S T S Y F F G H F F S R H D F S G S T D 41138 tttaacagggaacaacttcctccaaatcatgtcgaacattcaagtcaacttcaacaatgcttccggcgcttacggatccactat 29 F N R E Q L P P N H V E H S S Q L Q Q C F R R L R I H Y 41222 ccaagcatttcacgctga 41239 57 P S I S R * dplORF120 28387 gtgttgaagcgcaagcagaatacatgcgtatgcaattgcttcaatacggtaaattcactgtcaaatcaactaacagcgaggtc 1 V L K R K Q N T C V C N C F N T V N S L S N Q L T A R L 28471 aatacacttacgactacaacatggatgctaagcaacaatatgcagtcactaagaaatggactaacccagctgaaagtgacccta 29 N T L T T T T W M L S N N M Q S L R N G L T Q L K V T L 28555 tcgctgacattttag 28569 57 S L T F * dplORF121 39222 gtgcagacggatcacgtgagttcagtttggaagataataatcaacaatatatgggttattactccgattatgagcaagcagata 1 V Q T D H V S S V W K I I I N N I W V I T P I M S K Q I 39306 gcagggatcgaactaagtatcgatggtttgaccgccttgccaatgttcaagtgggaggtcgaaacgagttccttaattctttat 29 A G I E L S I D G L T A L P M F K W E V E T S S L I L Y 39390 ttgaatttggtttaa 39404 57 L N L V * dplORF122 40402 atgttattctccttatcctacataccgaatcacgttcatgtctggattaaacgagtattgttccgttctaaatcggccgacttg 1 M L F S L S Y I P N H V H V W I K R V L F R S K S A D L 40318 aatggattgggtaaagatcccgttatcgatgtgaatgaacccttgcgtaaggtacataacttcattccctgcggagaacataga 29 N G L G K D P V I D V N E P L R K V H N F I P- C G -E--H R 40234 aattcggtcacttga 40220 57 N S V T * dplORF123 21327 atggttcgacttttcgaaggattgaggttttcgaaccggttgagtttttcgagcattctcgacttttcgacccctttctatgct WO 00/32825 PCT/IB99/02040 387 1 M V R L F E G L R F S N R L S F S S I L D F S T P F Y A 21243 cgacttttcgagtgttttgaggttttcgagcaggttcgacttttcgagaaattgagtttttcgacctctaaattaggctcgatt 29 R L F E C F E V F E Q V R L F E K L S F S T S K L G S I 21159 attcgaaaagtttag 21145 57 I R K V * dplORF124 17891 atggtaaaagttaaagatttgcaagtaggaatgaaagttgtaaatgcaaaaggtactgaatttaaagtaactgaccgtcaaggt 1 M V K V K D L Q V G M K V V N A K G T E F K V T D R Q G 17807 cgtaaatgggtaagcctagaacgtcttagtgatggacgtattcggttctatgataacgaatcactaatggacgaaaaagtggag 29 R K W V S L E R L S D G R I R F Y D N E S L M D E K V E 17723 gtagtaaaatga 17712 57 V V K * dplORF125 49916 atgtcctcagccgcttccgttaaaattggaacaagtgaattatatagatgctcctcttttagcttgtcgataaggtattcatca 1 M S S A A S V K I G T S E L Y R C S S F S L S I R Y S S 49832 gtttcgccaatttcgaaaaattcgaatccaggaaaatggtcgagaatagtttcgtcgtccggaactcttccatatctcgaaaag 29 V S P I S K N S N P G K W S R I V S S S G T L P Y L E K 49748 tgttcttga 49740 57 C S * dplORF126 16136 atgagctcaagtacgttttctcgaacaatagggtcaagtccagttatatcaacgaactgtatatcgtcctcttgtataggaata 1 M S S S T F S R T I G S S P V I S T N C I S S S C I G I 16052 aggtctgcgtacagttgcatggctgaccctttaattggagtaactgttccttcactgtttattttaaataaggttatcatttct 29 R S A Y S C M A D P L I G V T V P S L F I L N K V I I S 15968 atcctctaa 15960 57 I L * dplORF127 13511 atgctaaatagctttcccattcaccgtcgctgttcttgcgccatttttcagtttcacgatactgaccaactttgcaaaggtcgt 1 M L N S F P I H R R C S C A I F Q F H D T D Q L C K G R 13427 gaaatagtgctacgattgcaactgtttccattgggtaaatgtcttcccagcctttgcctaccatggtatccatttcgaaaagta 29 E I V L R L Q L F P L G K C L P S L C L P W Y P F R K V 13343 gttgattga 13335 57 V D * dplORF128 4852 atgacagcagttcaacaagttaagttctacttagaagaagccggcgctcactttctaaaagatgttgagtacagtgacaactta 1 M T A V Q Q V K F Y L E E A G A H F L K D V E Y S D N L 4936 gagcaagcaattatgaaagatattcttaaatggaatggcgctcatagagatgagcacgatatgaaaataacttcatacgaagta 29 E Q A I M K D I L K W N G A H R D E H D M K I T S Y E V 5020 ttatag 5025 57 L * dplORF129 25133 atgaactttctgctaagcaacttgcgctcactgaagttcaaactaatgtacgcagccaccaatcttacattgaagaattcagta 1 M N F L L S N L R S L K F K L M Y A A T N L T L K N S V 25217 agaaggaaaaggcggacaaggaatgggaacgcattttggaagaacttgctcagcttgacgaaatctcagctggagcattgcctg 29 R R K R R T R N G N A F W K N L L S L T K S Q L E H C L 25301 tattag 25306 57 Y * dplORF130 16789 gtgcttgactttattcctttattatcgtataatcataatataaataaaacaagcgtcaaggacgcagaaagaggtcaattatgg 1 V L D F I P L L S Y N H N I N K T S V K D A E R G Q L W 16705 aaacaacactttatttcggttatcttacagcagattggaaagacggtcacaagaactacactttccactatgaaagcattcctg 29 K Q H F I S V I L Q Q I G K T V T R T T L S T M K A F L 16621 taa 16619 57 * dplORF131 43846 atgctcaaccggctgagaagaaacttggctggcagaaagatgctactggtttctggtacgctcgagcaaacggaacttatccaa 1 M L N R L R R N L A G R K M L L V S G T L E Q T E L I Q 43930 aagatgagttcgagtatatcgaagaaaacaagtcttggttctactttgacgaccaaggctacatgctcgctgagaaatggttga 44013 29 K M S S S I S K K T S L G S T L T T K A T C S L R N G * dplORF132 15304 gtgactggaaggtcatctaatacacatagcctcaagacatttcgttggctttcaggaaaacattcgactagattgtcaatgtat 1 V T G R S S N T H S L K T F R W L S G K H S T R L S M Y 15220 cccacaaaggcttcaaggttttcgagttcttcgccgtggtcctttacagcaagaaggaagtttattcgacctcttgcacgttga 15137 29 P T K A S R F S S S S P W S F T A R R K F I R P L A R * dplORF133 8061 atgacttcttcattcatgacaagttttcgagtttctgcttgcttgtcaggaatagttttcccggcggctaaaatgtatagatta 1 M T S S F M T S F R V S A C L S G I V F P A A-K M-Y- R L 7977 tcgtatttttctttcctgatagcagaacttgaatccatttgtattcccaccatttccgccctatctgcggcgaaataa 7900 29 S Y F S F L I A E L E S I C I P T I S A L S A A K * dplORF134 498 atgacttcaatgtacttaggttccatcaattcatacaagtcattcaaaataatgttcatgcaatcttcgtggaagtcaccgtgg 1 M T S M Y L G S I N S Y K S F K I M F M Q S S W K S P W 414 ttacggaaactgaataagtacaatttcaatgatttagattcaaccatcttttcgtttggaatgtaa 349 WO 00/32825 PCT/IB99/02040 388 29 L R K L N K Y N F N D L D S T I F S F G M * dplORF135 780 atgaagcagaacttgaaaatgctgctaatgttgcaatgttctacggagtcaagttcaccattcttgaaattgactcgaaaatct 1 M K Q N L K M L L M L Q C S T E S S S P F L K L T R K S 864 actcaagctctagctcttccttattacaaggaaaaggcgaaatttcacatggaaaatcttacgctgaaatcctag 938 29 T Q A L A L P Y Y K E K A K F H M E N L T L K S * dplORF13 6 55252 gtgaagaaatcttcaataaccttattcgcttctttgacagatacattcatctgctcagcgattgagttagccccgcggccgtac 1 V K K S S I T L F A S L T D T F I C S A I E L A P R P Y 55168 ataagacctaaaagaacggacttgacagaatttcttcgaagttttccttccttgttagtcgttccgtcgggatag 55094 29 I R P K R T D L T E F L R S F P S L L V V P S G * dplORF137 37146 atgcttcgaacttgtttgttagcaccgtcaggaggacaaactagtcgaacccattcacctgcgtctttgataatatctagcgcg 1 M L R T C L L A P S G G Q T S R T H S P A S L I I S S A 37062 acagcgcctacagaagaagcaacgtgtttcaacttcctaggcaagccttctgctagttcataccataatgcgtag 36988 29 T A P T E E A T C F N F L G K P S A S S Y H N A * dplORF138 30662 atgactatatcgaagaacaatgtagtcatccggcctatctgtatcttgctcgtcaaattcaactcctggaagcataggagcagg 1 M T I S K N N V V I R P I C I L L V K F N S W K H R S R 30578 cgagagctgaaatgtaggaagaatttccttcaatctgtccatcattgtcgttcgtttagtcatgttcactcctag 30504 29 R E L K C R K N F L Q S V H H C R S F S H V H S * dplORF139 12092 atgatactaaatcactcaacttgtttgaccctcctgataaattcgttcacgcagacacgcgcatttgagccctttttagatacc 1 M I L N H S T C L T L L I N S F T Q T R A F E P F L D T 12008 tttcgcaaacacctagatgcttccctcactaaaaggtcatgggcctcaagttcttcgaaagacatttctacatag 11934 29 F R K H L D A S L T K R S W A S S S S K D I S T * dplORF14 0 20562 atgttttcgatatttcctgcgcctaagacttcagcttggtcattgttcactaccattaggtattcattagtaagtgctttagca 1 M F S I F P A P K T S A W S L F T T I R Y S L V S A L A 20646 aagtttgaaaatttcattttattttccctttatttgtttttctttatactattattatacaataatgattga 20717 29 K F E N F I L F S L Y L F F F I L L L Y N N D * dplORF141 42922 gtgctaagagttgtagagatatcctctaaaacgctcttggctttattegatttccattcgaataacttatttagtaggacagta 1 V L R V V E I S S K T L L A L F D F H S N N L F S R T V 42838 agcactccgctgcacgctgtaataatcgtcgtcaagactgctgtgtcgtttagccacattggcatagattga 42767 29 S T P L H A V I I V V K T A V S F S H I G I D * dplORF142 31898 gtgactgtcgaagtttctccaaacagttctgtcactttacctaaaagcgtattagggattttcccgttagcgattaggttcatg 1 V T V E V S P N S S V T L P K S V L G I F P L A I R F M 31814 acacctgctgctcgaattttaacatggataggttcactaccttttgaaaatcctggaagtgcgatgatttga 31743 29 T P A A R I L T W I G S L P F E N P G S A M I * dplORF143 7565 atgaagtttgggttgacgcttttaactccagaccgtttaattttttcaaggcttgaaattggataccatataatcttttcatgc 1 M K F G L T L L T P D R L I F S R L E I G Y H I I F S C 7481 ttttggaaatacactaaaattccggcgagaataaatttgcatccatctgcgcgtgatagctggaaccattga 7410 29 F W K Y T K I P A R I N L H P S A R D S W N H * dplORF144 36517 gtgcaaatcaagcgactaacttatttagatacattaaacgaggcgcattcttcaagattcctaatggaaattcaacaattacca 1 V Q I K R L T Y L D T L N E A H S S R F L M E I Q Q L P 36601 ttgaataccgagccgatgacgcagcagcttggacctctactcttcccgctcaagttgaactgtttctaa 36669 29 L N T E P M T Q Q L G P L L F P L K L N C F * dplORF145 42067 atggaaacagctggagacctaacaagtggaaagaggttctatttaagcaagacttcgaacagaataattggcagaaacttgttc 1 M E T A G D L T S G K R F Y L S K T S N R I I G R N L F 42151 ttcaaagtgggtggaaccatcactcaacctatggcgacgcattctattcgaaaactcttgacggcatag 42219 29 F K V G G T I T Q P M A T H S I R K L L T A * dplORF146 51484 atgacaaactgcatgattgcatcacctttccagtacggaacctcaagggcgaaacagtattcttcaaccgtcgaagtgttcgtt 1 M T N C M I A S P F Q Y G T S R A K Q Y S S T V E V F V 51568 ctaagtttcaccagtacggtgaagatgaccctaaaacggaatttctttatggccaatatgagcttgtag 51636 29 L S F T S T V K M T L K R N F F M A N M S L dplORF147 55207 atgtatctgtcaaagaagcgaataaggttattgaagatttcttcaccgagttccctaaagtggcagactatatcatattcgttc 1 M Y L S K K R I R L L K I S S P S S L K W Q T I S Y S F 55291 aacagcaggcgcaggacttgggatatgttcaaacagctaccggtcgaagaagaaggcttcctgatatga 55359 29 N S R R R T W D M F K Q L P V E E E G F L I * dplORF148 28636 gtgtttcggttcaagaccattcgagtagggcgaacacctgtacgattttcgatgtcatccattgctgctaaaatgtcagcgata 1 V F R F K T I R V G R T P V R F S M S S I A A K M-S - I 28552 gggtcactttcagctgggttagtccatttcttagtgactgcatattgttgcttagcatccatgttgtag 2&484 29 G S L S A G L V H F L V T A Y C C L A S M L * dplORF149 26474 atgccattgaacttttcgagcataaggattaaccttgccccattgtctcactccagctgtggcggaatggctaatggtagttcg 1 M P L N F S S I R I N L A P L S H S S C G G M A N G S S 26390 agcaagtcgaagggcattgtattcgagattttgatatttatgagcagcaggtttccctag 26331 WO 00/32825 PCT/IB99/02040 389 29 S K S K G I V F E I L I F M S S R F P * dplORF150 15185 gtggtcctttacagcaagaaggaagtttattcgacctcttgcacgttgatagtcttcgcgaagttcgacgattcgtttgttcat 1 V V L Y S K K E V Y S T S C T L I V F A K F D D S F V H 15101 ttgctttcgctgattgttcatgcaataggctcctcgtatttaatagtttcacaagttgcgtcgacgtag 15033 29 L L S L I V H A I G S S Y L I V S Q V A S T * dplORF151 28027 atgattatatcaacgcaggggagattgctagctacattcaagcacttccttcaaacgctcttcaataccttggaccaactcttt 1 M I S T Q G R L L A T F K H F L Q T L F N T L D Q L F 28111 tccctaatgctcaacaaacagggacagacatttcatggctcaagggtgcaaataatttgccagtaa 28176 29 S L M L N K Q G Q T F H G S R V Q I I C Q * dplORF152 42235 atgtgcataaaggacttatcgacaaagaggctactattgcagtacttcctgaaggatttagaccgaaagtttcaatgtatcttc 1 M C I K D L S T K R L L L Q Y F L K D L D R K F Q C I F 42319 aggctctcaataactcatatggaaatgccattctatgtatatacactgacggaagacttgtggtga 42384 29 R L S I T H M E M P F Y V Y T L T E D L W * dplORF153 22307 atggtggacaaagggctcaccttttcgaactttcgatatcgtcatagcagacggttccattcgttcaggaaaaacagtatcgat 1 M V D K G L T F S N F R Y R H S R R F H S F R K N S I D 22391 ggctctttcattttccctttgggccatgacggaattcaacggacaaaactttgccatctgtggtaa 22456 29 G S F I F P L G H D G I Q R T K L C H L W * dplORF154 18446 gtgacaataggctttaagaactgcaaaaaaacctggggcgtctgcacgcgcaacctggagctccttaacagtcatccaaggctg 1 V T I G F K N C K K T W G V C T R N L E L L N S H P R L 18530 aggtttcttacaaacaatcctaattccttcaaaatagctcttgtccgggtcaatagtgcctaa 18592 29 R F L T N N P N S F K I A L V R V N S A * dplORF155 13512 atgaatacgaccctgagcaacttacaatgggacatggtgcaaaatctaatttccttcttcaacgtttcattcaactcacgccag 1 M N T T L S N L Q W D M V Q N L I S F F N V S F N S R Q 13596 ttgaagctcaagcaattttctggcatatgggagcctatgatattagtccttatgcaaatttga 13658 29 L K L K Q F S G I W E P M I L V L M Q I * dplORF156 18777 atgctagtatctccatttctgttggtcttgctttttagctctgttcagttcagctgcttctcgcgatgcaatagtttcgagaat 1 M L V S P F L L V L L F S S V Q F S C F S R C N S F E N 18861 atgcctgttcataggctcacaatattccgccaaagatttgccagttatggtggcgtcaattaa 18923 29 M P V H R L T I F R Q R F A S Y G G V N * dplORF157 13281 gtgcttgctggacttgagaagaaattggtatcattttcgagccaatccataaggttctcgataccgtcacgattgattgtttct 1 V L A G L E K K L V S F S S Q S I R F S I P S R L I V S 13197 gttactgctttcttgaagcgttttttaaagtctgtcatattagacccctttcattttctataa 13135 29 V T A F L K R F L K S V I L D P F H F L * dplORF158 40727 gtgaacgccgttattagggtcaaacgaagcccaaacggacattgtctttgtcccgtcactattgtgaggaacagtcacttctcc 1 V N A V I R V K R S P N G H C L C P V T I V R N S H F S 40643 acttgcgagcgttacctcttcgccggacgtgtcgtagtctgggtgactgctatgaacacttga 40581 29 T C E R Y L F A G R V V V W V T A M N T * dp1ORF159 30371 atgatttggtctgcgcttacccaagcagcttctcctttgagtttctgtcgagcattccctgtacggtctgtccaaatagcatgc 1 M I W S A L T Q A A S P L S F C R A F P V R S V Q I A C 30287 gtctttgcgtattcttccatcttagtagcagcgacttcgcagactgttatgacagcgacttga 30225 29 V F A Y S S I L V A A T S Q T V M T A T * dplORF160 41324 atgggttacagacacgcgaggaaaacaatcgaacgtccaagacgtatctatcaatgttatagaatactatggaccgtctatcaa 1 M G Y R H A R K T I E R P R R I Y Q C Y R I L W T V Y Q 41408 tttctccgttcaacgtactcgtcaaaatcctgcaattatccaagctcttcgaaatgctaa 41467 29 F L R S T Y S S K S C N Y P S S S K C * dplORF161 52175 atgcaaaaaggtttaaatgcttatctcgacatgacattgaaagcattgcattcgagactatttcaaaatgtttggcaacgttca 1 M Q K G L N A Y L D M T L K A L H S R L F Q N V W Q R S 52259 aatcaaaccaaggggccaagttttcaacttaccttacaagactcttcaagaatagaatag 52318 29 N Q T K G P S F Q L T L Q D S S R I E * dplORF162 13020 atgacagaagttgcggtaaatagcccgcaaaaggtgagagtagttatggtcgggaatattgaatttctcgaatatttaaaaagg 1 M T E V A V N S P Q K V R V V M V G N I E F L E Y L K R 13104 aagtacggaacagaaacttccatcagttatattatagaaaatgaaaggggtctaatatga 13163 29 K Y G T E T S I S Y I I E N E R G L I * dplORF163 40224 gtgaccgaatttctatgttctccgcagggaatgaagttatgtaccttacgcaagggttcattcacatcgataacgggatcttta 1 V T E F L C S P Q G M K L C T L R K G S F T S I T G S L 40308 cccaatccattcaagtcggccgatttagaacggaacaatactcgtttaatccagacatga 40367 29 P N P F K S A D L E R N N T R L I Q T * dplORF164 6696 atgtactcttggagaacttcgtgcctaaatgttccagcttcgcccattgcaattaggttagaatctgcgttatctataatagac 1 M Y S W R T S C L N V P A S P I A I R L E S A L S I I D 6612 tcaccgattctttcgaaatacatttttcgaatacatccaccaaccccgctgggcttataa 6553 29 S P I L S K Y I F R I H P P T P L G L * WO 00/32825 PCT/IB99/02040 390 dplORF165 50504 atgagtgaaagctggtcaatccccaccacagatggtctatatttagatatcatgctatctaaaattgcaggggtaaggttcttt 1 M S E S W S I P T T D G L Y L D I M L S K I A G V R F F 50420 cctccaatcataaagggcgtgactaccacaagggaattttcagcctcagtcattgcttga 50361 29 P P I I K G V T T T R E F S A S V I A * dplORF166 23519 gtggtcatgctctttaatgactctatcttctcccgtttggctcgctttactgtcccagctgtaagcatagtattcatcaatgtc 1 V V M L F N D S I F S R L A R F T V P A V S I V F I N V 23435 gtgcgtgttgctagggtcgagtgtaaatctattctcagccaagagttcagcgtgaaatga 23376 29 V R V A R V E C K S I L S Q E F S V K * dplORF167 1008 atgcttattcggttggagcttcttacgtcgtatatggtgctcacgcagacgatgcggctggaggtgcttaccctgattgcactc 1 M L I R L E L L T S Y M V L T Q T M R L E V L T L I A L 1092 ctgagttctataattcaatgtcaaatgcaatggaatatggaactggaggcaaggtaa 1148 29 L S S I I Q C Q M Q W N M E L E A R * dplORF168 54345 atgagactttttccaggttatattcttcacattgttcagttcctggagtcaagtattgttcttgaaattcatagagttcgaaag 1 M R L F P G Y I L H I V Q F L E S S I V L E I H R V R K 54261 tttgcaaagggtcataggccgcatacatataggcaacatcaggaggaattaaactaa 54205 29 F A K G H R P H T Y R Q H Q E E L N * dplORF169 45954 atgaacacagcatcgcgaagagtttcaatgttagtgataaggaagaattcgtcgtggccaccaagcaagtcttctgcccgttta 1 M N T A S R R V S M L V I R K N S S W P P S K S S A R L 45870 gaaactccgtcaatcactaatttcccatctttagtgactcgacttcctaaaatatga 45814 29 E T P S I T N F P S L V T R L P K I * dplORF170 27600 atgatgattgttcttgtgctcctgccgtttgttgagcagcagcaagttgcttaccaaaagagccgatttcacgaggttcgggaa 1 M M I V L V L L P F V E Q Q Q V A Y Q K S R F H E V R E 27516 caccaccaccgacacgacctggatttcctaaatttccagtcccggctggcgacttag 27460 29 H H H R H D L D F L N F Q S R L A T * dplORF171 47678 atgtcattttctttcatgtactcttttagagcatcacgaagacttttgacttgtttctccatgtcgcctttggtagcatttaat 1 M S F S F M Y S F R A S R R L L T C F S M S P L V A F N 47594 tcaccggcttcttcaattgcagcgatgaactgtttttcatcttcaaatttcatttaa 47538 29 S P A S S I A A M N C F S S S N F I * dplORF172 10462 atgtttcgaacattttctaccccattattagaagcagcatcaatttcaataggagagccaagtcctttgttcacatccttcgcg 1 M F R T F S T P L L E A A S I S I G E P S P L F T S F A 10378 aaaattcgagcagtagtggttttaccagttccagcgccaccacagaatagatag 10325 29 K I R A V V V L P V P A P P Q N R * dplORF173 32160 atgacattagacatttccttcgtctgtacgaaaggtttcagcttgagtcacttcaccgtacattgcactgaagattgtcataag 1 M T L D I S F V C T K G F S L S H F T V H C T E D C H K 32076 ttgctcatctgtcatatactcgccgacttcagcgtaagtaggctctaccattga 32023 29 L L I C H I L A D F S V S R L Y N * dplORF174 29766 atgtcccatcagcccttttcattaagattgtcgaaccagcgttcgacttttcatcagtttcaagctgttcttgcttatattggt 1 M S H Q P F S L R L S N Q R S T F H Q F Q A V L A Y I G 29682 cataatagaattgcgccatttgtttccagtagtctgcgtcaccttttagactga 29629 29 H N R I A P F V S S S L R H L L D * dplORF175 15648 atgcgcgtgatgtcatggcagataggcgaggataaagagtgtcgaatagaacgccgcagagcttacgagagcgccaaatacaag 1 M R V M S W Q I G E D K E C R I E R R R A Y E S A K Y K 15564 ggcgacggtactacggtggtcctcttgcttacctgtaaccaaataaaccattga 15511 29 G D G T T V V L L L T C N Q I N H * dplORF176 43031 gtgataaagacggtaacgttgaatttttctagttccgtcttgaatgacgtcattttggtgattgattgctactgtcgtttggtc 1 V I K T V T L N F S S S V L N D V I L V I D C Y C R L V 42947 aatcccgtcgacctgctgtttaagagtgctaagagttgtagagatatcctctaa 42894 29 N P V D L L F K S A K S C R D I L * dplORF177 19937 atgaacctaaacagttcgagacttctcaagctgttgggaaagaagcaggtcgaatattttggtgggaacgtgaacttggtcata 1 M N L N S S R L L K L L G K K Q V E Y F G G N V N L V I 19853 ttctcgcgactaattttaggtgcttttgtattaatcagcgtgatatgcgcttga 19800 29 F S R L I L G A F V L I S V I C A * dplORF178 11924 atgacaactgtcgaccaatttaaaagacagttgaggaaaagtttaggctcaatttttccttcatcagtttccttaaatttgasc 1 M T T V D Q F K R Q L R K S L G S I F P S S V-S L_ N- L 11840 caattagtaacctttagcgaattgctagcacttgcctcccatattaagtcataa 11787 29 Q L V T F S E L L A L A S H I K S * dplORF179 56058 atgggtagggttattccttacctcgttgatttgctttatgcaaaacctaccacaatcgcttgtcgtggcttcaggagttgcatt 1 M G R V I P Y L V D L L Y A K P T T I A C R G F R S C I 56142 ttggataagtcaaaaagcaagtgtctttatattcgacaagctctcgaataa 56192 WO 00/32825 PCT/IB99/02040 391 29 L D K S K S K C L Y I R Q A L E * dplORF180 41176 atgttcgacatgatttggaggaagttgttccctgttaaaatCtgtcgaaccgctgaagtcgtgtctactaaagaaatgcccgaa 1 M F D M I W R K L F P V K I C R T A E V V S T K E M P E 41092 aaagtaggacgtactgaatcggggatgttgaacctccatccgtttgaatag 41042 29 K V G R T E S G M L N L H P F E * dplORF181 13126 atggaagtttctgttccgtacttcctttttaaatattcgagaaattcaatattcccgaccataactactctcaccttttgcggg 1 M E V S V P Y F L F K Y S R N S I F P T I T T L T F C G 13042 ctatttaccgcaacttctgtcataggctgtcctcctttgcttatactgtaa 12992 29 L F T A T S V I G C P P L L I L * dplORF182 45369 gtgcttgcccatgtttcaataaatagggttcgacctcgcctagctttcgaacgtgctataacgatttcaatcatagcgaagaaa 1 V L A H V S I N R V R P R L A F E R A I T I S I I A K K 45285 ggtgagaagcttcaatcaattccattgcggtgtcaatatcttcttccttga 45235 29 G E K L Q S I P L R C Q Y L L P * dplORF183 13896 gtgattccagcttttggtttttcttcagcctcttcaactttttcttccttaggcgcaggtttcttacgagttgaactcttaggt 1 V I P A F G F S S A S S T F S S L G A G F L R V E L L G 13812 ttttcttcaactacttcttcaacctcagcctcttgttcaactggaccttga 13762 29 F S S T T S S T S A S C S T G P * dplORF184 53330 gtgaacttgccgtcaaccacgtcaaacatttggtcttcgtcgaggtctaaaattagagttccaagaagttcgctcttttctgga 1 V N L P S T T S N I W S S S R S K I R V P R S S L F S G 53246 aaatcttcaagagtagcactgtcttccggacgctctggaaggaattcataa 53196 29 K S S R V A L S S G R S G R N S * dplORF185 22522 atgaaattcgagatgttcgaaatgaaaatctacttattattagacactttagaaatggcgaagaaattgtcaactacttctata 1 M K F E M F E M K I Y L L L D T L E M A K K L S T T S I 22606 tatttggaggaaaagatgagtcgagtcaagaccttatacagggggtaa 22653 29 Y L E E K M S R V K T L Y R G * dplORF186 21272 atgctcgaaaaactcaaccggttcgaaaacctcaatccttcgaaaagtcgaaccattcgaaaagttcaaaagttcgaaaaactc 1 M L E K L N R F E N L N P S K S R T I R K V Q K F E K L 21356 aaccattcgagagtaggaattaaggacataccagttcaacctttttag 21403 29 N H S R V G I K D I P V Q P F * dplORF187 34415 atggtcttgttcaatctcttcctactatcattcaagcagctgttcaaattatcactgctttattcaatggtcttgttcaggcac 1 M V L F N L F L L S F K Q L F K L S L L Y S M V L F R H 34499 ttcctacgcttattcaagcaggtcttcaaattttgtcagctctcataa 34546 29 F L R L F K Q V F K F C Q L S * dplORF188 35609 atgttcgtaaagcagccggttcgcctcgagtggacttgttcaatacaggaagtgacaaccctaaccaacctcagtcacaatcta 1 M F V K Q P V R L E W T C S I Q E V T T L T N L S H N L 35693 aaaacaatcaaggcgagcaaaccgttgtcaacattggaacaatcgtag 35740 29 K T I K A S K P L S T L E Q S * dplORF189 42587 atgcaaacgcagtatcaaccgtctctgaaactcttcatgacccagacttgtatgctgcgaaccgtcgagaacttcgagctgacg 1 M Q T Q Y Q P S L K L F M T Q T C M L R T V E N F E L T 42671 agcaaaaacttcgcgaaactcgttacgcaatcgaagatgaaattctag 42718 29 S K N F A K L V T Q S K M K F * dplORF190 39786 atgtattcactcaaagttgttcagtgtggctcaatcatattaaaatcgaacttggtaatatctctactccttttagtgaagcag 1 M Y S L K V V Q C G S I I L K S N L V I S L L L L V K Q 39870 aggaagaccttaaatatcgaattgactcaaaagccgatcaaaagctaa 39917 29 R K T L N I E L T Q K P I K S * dplORF191 40996 atgtccattgttccggaacttgatttaggtaagtaccttgctaagtccagtgacggcgtaaaggatacgctagtagtatggttc 1 M S I V P E L D L G K Y L A K S S D G V K D T L V V W F 40912 ttacctaaatctatccagtcgctaccgaaaactcggtaccaaacttga 40865 29 L P K S I Q S L P K T R Y Q T * dplORF192 2920 atggtcgacgtcgaatgttttttcgagatgaagtttagggtcttctcgataccctacggtatgttcagcgagtgctttaacaaa 1 M V D V E C F F E M K F R V F S I P Y G M F S E C F N K 2836 acggaatggagtatcttgcaacccgtcacgttctgcgtcctcgcctaa 2789 29 T E W S I L Q P V T F C V L A * dplORF193 42456 atgatttcagctcaaattaaatacgaaatgagacattgtctaaatttaaccaagaattatctacattcgatttcaceacaagtc 1 M I S A Q I K Y E M R H C L N L T K N Y L H S IS P Q V 42372 ttccgtcagtgtatatacatagaatggcatttccatatgagttattga 42325 29 F R Q C I Y I E W H F H M S Y * dplORF194 40284 atgaacccttgcgtaaggtacataacttcattccctgcggagaacatagaaattcggtcacttgataccttaatggtagagcta 1 M N P C V R Y I T S F P A E N I E I R S L D T L M V E L WO 00/32825 PCT/IB99/02040 392 40200 ccgtcgttcttaccgataattagaccttcattagaagagctcatgtaa 40153 29 P S F L P I I R P S L E E L M * dplORF195 42584 atgttcacaatcgttgttttgacaagtttcttttcagctccttgtccaatagtgaactctgccacaatttggcgcgattttgta 1 M F T I V V L T S F F S A P C P I V N S A T I W R D F V 42500 aggttcaacatagttctcacctcctttctaaaaaatattataacatga 42453 29 R F N I V L T S F L K N I I T * dplORF196 11273 atggtagatttaacaagtccctgtccaatcatgtcactcctccttgctcatcaaaagaagtttggtttcaattatcggtttagc 1 M V D L T S P C P I M S L L L A H Q K K F G F N Y R F S 11189 attaggctcccatttaacaactccagcaagttcattcatttcttctag 11142 29 I R L P F N N S S K F I H F F * dplORF197 7484 atgaaaagattatatggtatccaatttcaagccttgaaaaaattaaacggtctggagttaaaagcgtcaacccaaacttcatcg 1 M K R L Y G I Q F Q A L K K L N G L E L K A S T Q T S S 7568 atgcagggtatgaagtttcttacaagaagcgtcgaactagattga 7612 29 M Q G M K F L T R S V E L D * dplORF198 24119 atgccgctcaacaaattgacgtccagttttattcaatgcctcagttcacctatacagttgaccctagaaacccttccagcttgc 1 M P L N K L T S S F I Q C L S S P I Q L T L E T L P A C 24203 tttctgttgacattgtttatcaggacgagcgtacaaaaggaatga 24247 29 F L L T L F I R T S V Q K E * dplORF199 15742 gtggctcctgaattaggctgtacttttcctcccaactgcttagcaactgccttctcttgtttagcactagctctgcgcgtggga 1 V A P E L G C T F P P N C L A T A F S C L A L A L R V G 15658 attggtttgtatgcgcgtgatgtcatggcagataggcgaggataa 15614 29 I G L Y A R D V M A D R R G * dplORF200 47843 atgacaggcttgtattcgataagccctgaaagtttttcacacatttcttccgtctcggcttcgtcaactaatttttcgataatt 1 M T G L Y S I S P E S F S H I S S V S A S S T N F S I I 47759 tctttcaagcgttcttCgtcCatagttgagCgCtctgtcgtgtag 47715 29 S F K R S S S I V E R S V V * dplORF201 38569 atgggcttcacaagttccttctttaatcaaaggtcaatatctttggactcgaactatttggacctataccgattcaactaccga 1 M G F T S S F F N Q R S I S L D S N Y L D L Y R F N Y R 38653 aacgggctatcaaaaaacctacattccaaaagacgggaatga 38694 29 N G L S K N L H S K R RE * dplORF202 44483 gtggggcgtttattttttataaaaattttttacaaaatgcttgacaacattcactcattatcgtataatacaattataaaaata 1 V G R L F F I K I F Y K M L D N I H S L S Y N T I I K I 44567 aataaagccgaaaggcgaggaggacattatgtcaaaaattaa 44608 29 N K A E R R G G H Y V K N * dplORF203 22781 gtgattaggattggccgggttacaagagaaccacattttcgaacctgttacggaacagcgccctgtcgcttggttgacaaacga 1 V I R I G R V T R E P H F R T C Y G T A P C R L V D K R 22697 ttcaggcatcagtgccacctcatcacagaagatacctgctaa 22656 29 F R H Q C H L I T E D T C * dplORF204 1471 atgaccacggttcgagtcaagggatggttgttgacttttatcacgtcaagaaaatcgcaggtacattcattgacagacttgacc 1 M T T V R V K G W L L T F I T S R K S Q V H S L T D L T 1555 acgctgttcttcttcaagggaatgaaccaatcgctttag 1593 29 T L F F F K G M N Q S L * dplORF205 8524 gtgacactgatgaatggttctcagtttggtatgctactcgtgacgcagatatcttctacgaccaaagaattgcccaatttagaa 1 V T L M N G S Q F G M L L V T Q I S S T T K E L P N L E 8608 ttcaggaaaagcaacctgctatcaagttcaatttcgtag 8646 29 F R K S N L L S S S I S * dplORF206 19855 atgaccaagttcacgttcccaccaaaatattcgacctgcttctttcccaacagcttgagaagtctcgaactgtttaggttcatc 1 M T K F T F P P K Y S T C F F P N S L R S L E L F R F I 19939 aaattgttcaacttgagcaagtgcgatattattctttag 19977 29 K L F N L S K C D I I L * dplORF207 27502 gtgtcggtggtggtgttcccgaacctcgtgaaatcggctcttttggtaagcaacttgctgctgctcaacaaacggcaggagcac 1 V S V V V F P N L V K S A L L V S N L L L L N K R Q E H 27586 aagaacaatcatcattctttaaataataggaggaactaa 27624 29 K N N H H S L N N R RN * dplORF208 47279 atgtttggtatgaagcaaaagacttcgctgaagaaaataacattcacttcccgtttgttcttcctgaaac agacagaccttg 1 M F G M K Q K T S L K K I T F T S R L F F L N L E Q T L 47363 accatcgtggttctcgattctgggatgacgaaggcgtga 47401 29 T I V V L D S G M T KA * dplORF209 29784 atgttaagaatcaagttcgtagagccattgaaaccgctcctactaaaatcaaggtacttcgaaactcttgggtcagtgatggat WO 00/32825 PCT/IB99/02040 393 1 M L R I K F V E P L K P L L L K S R Y F E T L G S V M D 29868 atggaggaaagaaaaaggataaagcgaatgaagtcgtag 29906 29 M E E R K R I K R M K S * dplORF210 53077 atgtttcaacttttcccgtatcatggttgtaaagttgaagaaatagtttttcaatacgagggaatccgttttggcataatggac 1 M F Q L F P Y H G C K V E E I V F Q Y E G I R F G I M D 52993 aattatcaggatggactgtttccccgtcttcgccaatag 52955 29 N Y Q D G L F P R L R Q * dplORF211 20959 gtgctcgacttttatgtcgcccctaatttttgtttttacttacggactatgggatttgtaggtattttcagggcgcttttttat 1 V L D F Y V A P N F C F Y L R T M G F V G I F R A L F Y 20875 ttacttattaagtccttttctatattagattgtttataa 20837 29 L L I K S F S I L DCL * dplORF212 52983 atggactgtttccccgtcttcgccaatagcattgcaattgatatagcgtcgacgaccgtcaacgtctgcttcgtggactacgaa 1 M D C F P V F A N S I A I D I A S T T V N V C F V D Y E 52899 ataatccatgtcttcgccttccgggtcatcatacaatag 52861 29 II H V F A F R V I I Q * dplORF213 30291 atgcgtctttgcgtattcttccatcttagtagcagcgacttcgcagactgttatgacagcgacttgaaacttgtttcgataccg 1 M R L C V F F H L S S S D F A D C Y D S D L K L V S I P 30207 ttcacagttactaacaaattcttcaggcttccatactaa 30169 29 F T V T N K F F R L P Y * dplORF214 24273 atgatgccaaagttgtttttcagtgctcattccttttgtacgctcgtcctgataaacaatgtcaacagaaagcaagctggaagg 1 M M P K L F F S A H S F C T L V L I N N V N R K Q A G R 24189 gtttctagggtcaactgtataggtgaactgaggcattga 24151 29 V S R V N C I G E L RH * dplORF215 35822 atgttaccaaaccctgatagagtttctttacttctattatacaatcctctcgacagtttgtcaacgtcgtcattgtttcgaact 1 M L P N P D R V S L L L L Y N P L D S L S T S S L F R T 35738 acgattgttccaatgttgacaacggtttgctcgccttga 35700 29 T I V P M L T T V C SP * dplORF216 32849 atggcctcggagctcgcggccacatctcctccagatacggcagccaggtcaagtacccctggcatagcgtccatgatttcattt 1 M A S E L A A T S P P D T A A R S S T P G I A S M I S F 32765 acctggaaaccggctgaagctagattttccataccttga 32727 29 T W K P A E A R F SIP * dplORF217 23443 atgaatactatgcttacagctgggacagtaaagcgagccaaacgggagaagatagagtcattaaagagcatgaccactgcatgg 1 M N T M L T A G T V K R A K R E K I E S L K S M T T A W 23527 ataggaacagatatgcctgtctcactgacgctctaa 23562 29 I G T D M P V S L T L * dplORF218 22029 atggaatgcttccggaagaggttcgatatagactacaaattgagcgcgagaaaattacattgctccgggccaaaatgggcgacc 1 M E C F R K R F D I D Y K L S A R K L H C S G P K W A T 22113 aggaaattgaaggcgaggttaaagataacttcgtag 22148 29 R K L K A R L K I T S * dplORF219 51388 atgattttatgctcgactttttcagttctcccatttcttcgaaacgcttcagggctgacgccttgcctaactacttcgctagat 1 M I L C S T F S V L P F L R N A S G L T P C L T T S L D 51304 gttccaaaattccttttcagccactggtttccatag 51269 29 V P K F L F S H W F P * dplORF220 6334 gtgaagttttcttcggtgacggttgatacaatttccttcaagagtaagctgttaaggtggcaagtgaattctttcttcgaaact 1 V K F S S V T V D T I S F K S K L L R W Q V N S F F E T 6250 ttcttgccagcagatgcgtacatgatgtcttcataa 6215 29 F L P A D A Y M M SS * dplORF221 43507 atgactgctcaagttctatgtactatgctctccgctcagccggagcttcaagtgctggatgggcagtcaatactgagtacatgc 1 M T A Q V L C T M L S A Q P E L Q V L D G Q S I L S T C 43591 acgcatggcttattgaaaacggttatgaactaa 43623 29 T H G L L K T V M N * dplORF222 13212 gtgacggtatcgagaaccttatggattggctcgaaaatgataccaatttcttctcaagtccagcaagcactcgataccatggaa 1 V T V S R T L W I G S K M I P I S S Q V Q Q A L D T M E 13296 gctatgaaggtggacttgtcgagcactcattaa 13328 29 A M K V D L S S T H * dplORF223 14055 atgtggtggtacctgctggatatgttcgagatgtctactacttctacagtgaagtcgctgacgtttactacaagaaagatgtcg 1 M W W Y L L D M F E M S T T S T V K S L T F T T R K M S 14139 acgagcctgacgatgacagcgacattcttgtag 14171 29 T S L T M T A T F L * WO 00/32825 PCT/IB99/02040 394 dplORF224 13621 atgccagaaaattgcttgagcttcaactggcgtgagttgaatgaaacgttgaagaaggaaattagattttgcaccatgtcccat 1 M P E N C L S F N W R E L N E T L K K E I R F C T M S H 13537 tgtaagttgctcagggtcgtattcatatgctaa 13505 29 C K L L R V V F I C * dplORF225 32991 gtgagcaacgggtgcgacgtatttcatcgcctctgccatgtcgctagtttctgcgttcgtatcagctgctgctcgagcaaatac 1 V S N G C D V F H R L C H V A S F C V R I S C C S S K Y 32907 gtcagccacgtgacccgcctggtttgcctctaa 32875 29 V S H V T R L V C L * dplORF226 25191 gtggctgcgtacattagtttgaacttcagtgagcgcaagttgcttagcagaaagttcatcgctaggaattggatagtggtgttc 1 V A A Y I S L N F S E R K L L S R K F I A R N W I V V F 25107 gatagtcattgtcgtaagtgtttgataacttga 25075 29 D S H C R K C L I T * dplORF227 23115 atgactcaattagatggtagcgcttatgacgtttcgagaatccataaaggccgaaggttgttgcattatagataccaaagtcgc 1 M T Q L D G S A Y D V S R I H K G R R L L H Y R Y Q S R 23031 ctgctacgaataaacggtcgaattctatattga 22999 29 L L R I N G R I L Y * dplORF228 10450 atgttcgaaacattattgaagattctagatacaagtctatggacagcgagttcaaagtttacatcattgacgaggttcatatgc 1 M F E T L L K I L D T S L W T A S S K F T S L T R F I C 10534 tttcaaccggagcatttaatgcgctgttga 10563 29 F Q P E H L M R C * dplORF229 27634 atgtgcgagttaagaaaactgattttaatcaaaccactcgaagcattgtcgcaattcctgaccactacgttgctttggtgctc 1 M C E L R K L I L I K P L E A L S Q F L T T T L L W L L 27718 aaattccagctaccgcagcaactcaagtag 27747 29 K F Q L P Q Q L K * dplORF230 50723 gtgacgaaaaatccggcatacttgaactatctgtcgttaaaaaccgatatggcgaagaccgaaaaatcatcgaatatatgtggg 1 V T K N P A Y L N Y L S L K T D M A K T E K S S N I C G 50807 acgttgaaactggaacctatactcttatag 50836 29 T L K L E P I L L * dplORF231 31071 atgcgcgtgtcattgcgtttcacatcttcagttccctccgaggtcacggcttcgagttctgctgtttctgccgtatctacgaca 1 M R V S L R F T S S V P S E V T A S S S A V S A V S T T 30987 aagttagctccgccgacttttggcaactga 30958 29 K L A P P T F G N * dplORF232 29385 atgtcaattccattagctcttgctaattcaacgagctcaggaacggttttagccgcatactcttcgcgcatttgttcaacttcg 1 M S I P L A L A N S T S S G T V L A A Y S S R I C S T S 29301 tcaatttcttcaactgattcaattgtttga 29272 29 S I S S T D S I V * dplORF233 52892 atgtcttcgccttccgggtcatcatacaatagagtgacaattgcgctgtcaccgtggtcagcgagtgtgaaaaactcgttatta 1 M S S P S G S S Y N R V T I A L S P W S A S V K N S L L 52808 gaccctgagctaaatgttcctgatttttga 52779 29 D P E L N V P D F * dplORF234 36253 atgcttacgagtacagcgactcaactgttcgaaaggtttataagtttcaacccgctttgggaggcgatagcttacctaacccag 1 M L T S T A T Q L F E R F I S F N P L W E A I A Y L T Q 36337 gaagacctactcgacaatttagagtag 36363 29 E D L L D N L E * dplORF235 32768 atgaaatcatggacgctatgccaggggtacttgacctggctgccgtatctggaggagatgtggccgcgagctccgaggccatgg 1 M K S W T L C Q G Y L T W L P Y L E E M W P R A P R P W 32852 ctagttcacttcgagcctttggattag 32878 29 L V H F E P L D * dplORF236 37528 atgttcgtcgcttttagatttagcaatatatcgaggcttcatgtggcgtgtagtaaaccacgaaacatcaatgagatattcact 1 M F V A F R F S N I S R L H V A C S K P R N I N E I F T 37444 tccattgttgatagaagcaaacgttaa 37418 29 S I V D R S K R dplORF237 1678 gtgagagtccaggtaaggaatcttgacatattctcagccgtagttctaaatccaaatagaactcgcttggtgtsaaetgcattt 1 V R V Q V R N L D I F S A V V L N P N R T R L V-S T A F 1594 gctaaagcgattggttcattcccttga 1568 29 A K A I G S F P * dplORF238 1301 atgcctttttgcggtcgatacaagttgcgcaagttccacaactttcagcgtcactttcataacatgaacgagtcaagaaataag 1 M P F C G R Y K L R K F H N F Q R H F H N M N E S R N K WO 00/32825 PCT/IB99/02040 395 1217 gaacatctaaatcaattccccatttaa 1191 29 E H L N Q F P I * dplORF239 26521 atggtgaagtatttcctatcgaagaatgtcctttcgaccatcctaatggaatgtgctaccaaactgtatggtacgaaaactcac 1 M V K Y F L S K N V L S T I L M E C A T K L Y G T K T H 26605 tcgaagaaatcgctgatgagttga 26628 29 S K K S L M S * dplORF240 41893 atgtttggaataagcgtgaaacagagtttacatggcgaagtaacaaatacgaggacaaccctacgggaactcgaggtgaatggg 1 M F G I S V K Q S L H G E V T N T R T T L R E L E V N G 41977 gactatttcaaaatttctggttag 42000 29 D Y F K I S G * dplORF241 47020 gtgtctttccttaatatggagatagttttcattctatttaagcaggatatcgaaaaggttaccaattttagatttcataggctt 1 V S F L N M E I V F I L F K Q D I E K V T N F R F H R L 46936 accatctacgatataatctgctaa 46913 29 T I Y D I I C * dplORF242 41338 gtgtctgtaacccatgctcttacggtagcggagccattaaagttcatcatacccaatttgccgccgttttcgttgatagcttgg 1 V S V T H A L T V A E P L K F I I P N L P P F S L I A W 41254 tttttacctacgagctcagcgtga 41231 29 F L P T S S A * dplORF243 51306 atgttccaaaattccttttcagccactggtttccatagaaccctccatcgtttcgacctaatacattcgagacgaattcagtta 1 M F Q N S F S A T G F H R T L H R F D L I H S R R I Q L 51222 gtcctgaagtgtagccgcaagtga 51199 29 V L K C S R K * dplORF244 27083 gtgaggtacaaaatgttgaccgtcgccgtcaatgaaaattttagcatcgagttctttcgaagttttcgaaataatttccttcac 1 V R Y K M L T V A V N E N F S I E F F R S F R N N F L H 26999 ctgtttgatagttggttcatctag 26976 29 L F D S W F I * dplORF245 6278 gtggcaagtgaattctttcttcgaaactttcttgccagcagatgcgtacatgatgtcttcataactgctagtagaagttttaat 1 V A S E F F L R N F L A S R C V H D V F I T A S R S F N 6194 tcgaagtcggtctttcaagaataa 6171 29 S K S V F Q E * dplORF246 2831 atggagtatcttgcaacccgtcacgttctgcgtcctcgcctaatagaccaaaaagtctttgaacggctgcctcagtattgtcca 1 M E Y L A T R H V L R P R L I D Q K V F E R L P Q Y C P 2747 aggttacaatttcatccggcttaa 2724 29 R L Q F H P A * dplORF247 29641 gtgacgcagactactggaaacaaatggcgcaattctattatgaccaatataagcaagaacagcttgaaactgatgaaaagtcga 1 V T Q T T G N K W R N S I M T N I S K N S L K L M K S R 29725 acgctggttcgacaatcttaa 29745 29 T L V R Q S * dplORF248 53560 gtgcaaagcctcgttctagcaagaagaacgatgctcagttacttgctcaacggaaaaacaggaagcctgcagttgaggttactt 1 V Q S L V L A R R T M L S Y L L N G K T G S L Q L R L L 53644 acatttcaggaaacgctctaa 53664 29 T F Q E T L * dplORF249 2012 gtggatgcgactatcattgcaactggtgtgactcagcctttacctggaacggtactactgagccggaatatatcacaggcaaag 1 V D A T I I A T G V T Q P L P G T V L L S R N I S Q A K 2096 aagctgctagtcgaatcttga 2116 29 K L L V E S * dplORF250 23837 atgggcaaacatggaagattgacgaagactcagtcgactataaacctactcgagaaattcgaaactatattcgacaacttatca 1 M G K H G R L T K T Q S T I N L L E K F E T I F D N L S 23921 aaaagcaatcacgctttatga 23941 29 K S N H A L * dplORF251 39205 atggaaataattagtcttaccgtctgcgcctggcttcccgggtatcccttgagctccgtcattccccttccatttcgtccatgt 1 M E I I S L T V C A W L P G Y P L S S V I P L P F R P C 39121 ataggctgcagggtcttttga 39101 29 I G C R V F dplORF252 54771 gtgttgtataggtcgaaactaattttgcatattttctatatttcaaaagtgcttttgagatatcgttat-eaaaatgctcgacaa 1 V L Y R S K L I L H I F Y I S K V L L R Y R Y Q N A R Q 54687 tactttcgcctgttcctctag 54667 29 Y F R L F L * dplORF253 56255 atggttgcgtctataatagaaccgatgttgctagacaaagcatttgcaatcttcgagtctaatttattcgagagcttgtcgaat WO 00/32825 PCT/IB99/02040 396 1 M V A S I I E P M L L D K A F A I F E S N L F E S L S N 56171 ataaagacacttgctttttga 56151 29 I K T L A F * dplORF254 48479 atgaacctttcgcttaggttcaatctttttcgaacattttcatatttaacaaaactttcagctaaaaatcgacaaagttcaatg 1 M N L S L R F N L F R T F S Y L T K L S A K N R Q S S M 48395 ttcgactcaatgtttaaataa 48375 29 F D S M F K * dplORF255 9572 atgctttggtcttctcgacgaatgactctactacattccctgcagggtttcgagcagtacgggtcaatgatgcaccgttttcgt 1 M L W S S R R M T L L H S L Q G F E Q Y G S M M H R F R 9488 caaggtagtcaccttttctaa 9468 29 Q G S H L F * dplORF256 15289 atgaccttccagtcactaatgcggccgctgaaattggataccactatacatgggttcaccaacttcgagacaaagcagttgaaa 1 M T F Q S L M R P L K L D T T I H G F T N F E T K Q L K 15373 cacttgaagaaattttag 15390 29 H L K K F * dplORF257 28216 gtgaacgtgctggatttagcaaacaagctactgagatggcattcttccgtgagtctatgcgacttggtgaaaaagaccgtcaaa 1 V N V L D L A N K L L R W H S S V S L C D L V K K T V K 28300 acttgcaaatgctattga 28317 29 T C K C Y * dplORF258 44023 atggaaattggtattggttcgaccgtgacggatacatggctacgtcatggaaacggattggcgagtcatggtactacttcaatc 1 M E I G I G S T V T D T W L R H G N G L A S H G T T S I 44107 gcgatggttcaatggtaa 44124 29 A M V Q W * dplORF259 4298 atgactcgactacgaagcataaagacaagtggatggaaagagtattcgaagttattcgaaacagttctaatccagacgttaaga 1 M T R L R S I K T S G W K E Y S K L F E T V L I Q T L R 4382 ctcacgcatttgggatga 4399 29 L T H L G * dplORF260 24746 gtgaccctacttcctcaatcggcggtactggaggcaagcaagctcaagtcacttccatttcaggaaacttcaacttccttccag 1 V T L L P Q S A V L E A S K L K S L P F Q E T S T S F Q 24830 cggctgaatattatttag 24847 .29 R L N I I * dplORF261 288 atgaattcacttccctttgccctaaaacaggacagcctgacttcgcgaatgttttcattagttacattccaaacgaaaagatgg 1 M N S L P F A L K Q D S L T S R M F S L V T F Q T K R W 372 ttgaatctaaatcattga 389 29 L N L N H * dplORF262 9408 atgcctattcaactccaggcggaaagatgtggaagcatgcttgtgcagttcgacttaaatttagaaaaggtgactaccttgacg 1 M P I Q L Q A E R C G S M L V Q F D L N L E K V T T L T 9492 aaaacggtgcatcattga 9509 29 K T V H H * dplORF263 27052 atgaaaattttagcatcgagttctttcgaagttttcgaaataatttccttcacctgtttgatagttggttcatctagacctttt 1 M K I L A S S S F E V F E I I S F T C L I V G S S R P F 26968 aacaagtcttctaattga 26951 29 N K S S N dplORF264 6139 gtgaatagtacaaggcggtctaatacgctcaggatttctgctgtagggatagccgcatcatcttcaaactcaattgagtcaagc 1 V N S T R R S N T L R I S A V G I A A S S S N S I E S S 6055 tgtgaaacgtcttcataa 6038 29 C E T S S * dplORF265 4801 gtgaataaagtcaagcgtttttgtataaaaagttcatttttttttaaaaaaaataagagcgaaaagctcttatctaaaatagtc 1 V N K V K R F C I K S S F F F K K N K S E K L L S K I V 4717 gacgttgacgatttttaa 4700 29 D V D D F * dplORF266 50220 atgcccgttcttccaagcagttgcaagcattttatcaatagtccacgacttaccttgtccaggtcgagccattatgacaatcaa 1 M P.V L P S S C K H F I N S P R L T L S R S S H Y D N Q 50136 atcctcaccaggaagtaa 50119 29 I L T R K * dplORF267 47367 atggtcaaggtctgttctaggttcaggaagaacaaacgggaagtgaatgttattttcttcagcgaagtcttttgcttcatacca 1 M V K V C S R F R K N K R E V N V I F F S E V F C F I P 47283 aacattaatcgtagatag 47266 29 N I N R R * dplORF268 WO 00/32825 PCT/IB99/02040 397 12621 atgtcaatttcggtcttgtgcttgacaatggattcaactactgatgcgtcaacctttttcaatcgcgacagttgtccaattca 1 M S I S V L C L T M D S T T D A S T F F N R D S L S N S 12537 ttgtcaattctagagtaa 12520 29 L S I L E * dplORF269 53834 gtgaatagtatcgagtccatcagtttctacgtcaatagaacctattccgtcttcaatcattttgtctacatactgctcgagttt 1 V N S I E S I S F Y V N R T Y S V F N H F V Y I L L E F 53750 tgcttcctcagtgattaa 53733 29 C F L S D * dplORF270 50792 atgatttttcggtcttcgccatatcggtttttaacgacagatagttcaagtatgccggatttttcgtcacgcttcatagcgata 1 M I F R S S P Y R F L T T D S S S M P D F S S R F I A I 50708 actctgctagcattttga 50691 29 T L L A F * dplORF271 19739 atgaggctgctttgctttatcttcgttaccgtattgaccgacttcctactcgcgaaccttcctacaagaattcatacctcaaag 1 M R L L C F I F V T V L T D F L L A N L P T R I H T S K 19655 gctttttgtcagccttag 19638 29 A F C Q P * dp10RF272 1556 gtggtcaagtctgtcaatgaatgtacctgcgattttcttgacgtgataaaagtcaacaaccatcccttgactcgaaccgtggtc 1 V V K S V N E C T C D F L D V I K V N N H P L T R T V V 1472 ataagttccgcctgctaa 1455 29 I S S A C * dplORF273 56256 atggatttcattaggactgagtcctcttggaattggaacggttgcatatatagatattccgtcagccgtactaggccaagttct 1 M D F I R T E S S W N W N G C I Y R Y S V S R T R P S S 56340 agttcagtttatcttgcagtcaattgcttcgagatatttgaaaaagtagtcaggaaaattcctgattatcttgcagtcaattgc 29 S S V Y L A V N C F E I F E K V V R K I P D Y L A V N C 56424 ttcgagatatttgaaaaagtagtcaggaaaattcctgattattttttttacaaaaacgcttga 56486 57 F E I F E K V V R K I P D Y F F Y K N A * WO 00/32825 PCT/IB99/02040 398 Table 31 Query= sidI114822IlanidplORF0Ol Phage dpi ORF136698-4039012 (1230 letters) >gi928828 (L44593) ORF1904; putative (Lactococcus lactis phage BK5-T] Length = 1904 Score = 427 bits (1086), Expect = e-118 Identities = 226/475 (47%), Positives = 281/475 (58%), Gaps = 45/475 (9%) Query: 395 AESGKYIGVLNTNKKPSELVPDDFTWIRLEGPKGDAGLPGAPGRDGVDGVPGKSGVGIAD 454 A+ YIG + P D+TW + +G+ G GA G+DGV GK GVGI Sbjct: 820 ADYPSYIGQYTDFIQYDSAKPSDYTWSLI---RGNDGKDGATGKDGV---AGKDGVGIKT 873 Query: 455 TAITYAVSVSGTQEPENGWSEQVPELIKGRFLWTKTFWRYTDGSHETGYSVAYIGQDGNS 514 T ITYA+S SGT +P GW+ QVP L+KG++LWTKT W YTD S ETGYSV YI +DGN+ Sbjct: 874 TVITYALSSSGTDKPNTGWTSQVPTLVKGQYLWTKTVWTYTDSSSETGYSVTYIAKDGNN 933 Query: 515 GKDGIAGKDGVGIAATEVMYASSPSATEAPAGGWSTQVPTVPGGQYLWTRTRWRYTDQTD 574 G DGIAGKDGVGI T + YA S T APA GW++QVP VP GQ+LWT+T W YTD T Sbjct: 934 GNDGIAGKDGVGIKKTTITYAVGTSGTTAPASGWNSQVPNVPAGQFLWTKTVWTYTDNTS 993 Query: 575 EIGYSVSRMGEQGPKGDAGR -- DGIAGKNGIGLKSTSVSYGISPTDSAIP-GVWASQVP 630 E GYSV+ MG +G KGD G +GIAGK+G G+K+T+++Y SP + P G W++ VP Sbjct: 994 ETGYSVAMMGVKGDKGDPGNNGTNGIAGKDGKGIKATAITYQASPNGTTAPTGTWSASVP 1053 Query: 631 SLIKGQYLWTRTIWTYTDSTTETGYQKTYIPKDGNDGKNGIAGKDGVGIKSTTITYAGST 690 + KG +LWTRTIWTYTD+TTETGY Y+ +GN+G +G GKDG GIK+TTITYAGST Sbjct: 1054 PVAKGSFLWTRTIWTYTDNTTETGYAVAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGST 1113 Query: 691 SGTVAPTSNWTSAIPNVQPGFFLWTKTVWNYTDDTSETGYSVSKIGETXXXXXXXXXXXX 750 SGT P + WTS +P V G +LWTKTVW YTD+TSETGYSV+ +G Sbjct: 1114 SGTTPPNNGWTSTVPTVAEGNYLWTKTVWTYTDNTSETGYSVAMMG------VKGDKGDP 1167 Query: 751 XXXXXXXXXXADGRS-QYTHLAFSNSPNGEGFSHTDSGRAYVGQYQDFNPVHSKDPAAYT 809 DG+ + T + + SPNG A G + P +K +T Sbjct: 1168 GNNGTNGIAGKDGKGIKATAITYQASPNGT--------TAPTGTWSASVPPVAKGSFLWT 1219 Query: 810 WTKW ------------------ -KGNDGAQGIPGKPGADGKTNYFHIAYASSADGS 846 T W GN+G G PGK G KT I YA S G+ Sbjct: 1220 RTIWTYTDNTTETGYAVAYMGTNGNNGHDGFPGKDGTGIKTT--TITYAGSTSGT 1272 Score = 396 bits (1007), Expect = e-109 Identities = 208/449 (46%), Positives = 260/449 (57%), Gaps = 42/449 (9%) Query: 421 IRLEGPKGDAGLPGAPGRDGVDGVPGKSGVGIADTAITYAVSVSGTQEPENGWSEQVPEL 480 + + G KGD G PG +G +G+ GK G GI TAITY S +GT P WS VP + Sbjct: 1155 VAMMGVKGDKG--- DPGNNGTNGIAGKDGKGIKATAITYQASPNGTTAPTGTWSASVPPV 1211 Query: 481 IKGRFLWTKTFWRYTDGSHETGYSVAYIGQDGNSGKDGIAGKDGVGIAATEVMYASSPSA 540 KG FLWT+T W YTD + ETGY+VAY+G +GN+G DG GKDG GI T + YA S S Sbjct: 1212 AKGSFLWTRTIWTYTDNTTETGYAVAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGSTSG 1271 Query: 541 TEAPAGGWSTQVPTVPGGQYLWTRTRWRYTDQTDEIGYSVSRMGEQGPKGDAGR-- -DGI 597 T P GW++ VPTV G YLWT+T W YTD T E GYSV+ MG +G KGD G +GI Sbjct: 1272 TTPPNNGWTSTVPTVAEGNYLWTKTVWTYTDNTSETGYSVAMMGVKGDKGDPGNNGTNGI 1331 Query: 598 AGKNGIGLKSTSVSYGISPTDSAIP-GVWASQVPSLIKGQYLWTRTIWTYTDSTTETGYQ 656 AGK+G G+K+T+++Y SP + P G W++ VP + KG +LWTRTIWTYTD+TTETGY Sbjct: 1332 AGKDGKGIKATAITYQASPNGTTAPTGTWSASVPPVAKGSFLWTRTIWTYTDNTTETGYA 1391 Query: 657 KTYIPKDGNDGKNGIAGKDGVGIKSTTITYAGSTSGTVAPTSNWTSAIPNVQPGFFLWTK 716 Y+ +GN+G +G GKDG GIK+TTITYAGSTSGT P + WTS +P V G +LWTK Sbjct: 1392 VAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGSTSGTTPPNNGWTSTVPTVAEGNYLWTK 1451 Query: 717 TVWNYTDDTSETGYSVSKIGETXXYYYYYYYYYYXYYYXfGRS-QYTHLAFSNS 775 TVW YTD+TSETGYSV+ +G DG+ + T + + S Sbjct: 1452 TVWTYTDNTSETGYSVAMMG------VKGDKGDPGNNGTNGIAGKDGKGIKATAITYQAS 1505 WO 00/32825 PCT/IB99/02040 399 Query: 776 PNGEGFSHTDSGRAYVGQYQDFNPVHSKDPAAYTWTKW ------------------ -- KGND 817 PNG A G + P +K +T T W GN+ Sbjct: 1506 PNGT--------TAPTGTWSASVPPVAKGSFLWTRTIWTYTDNTTETGYAVAYMGTNGNN 1557 Query: 818 GAQGIPGKPGADGKTNYFHIAYASSADGS 846 G G PGK G KT I YA S G+ Sbjct: 1558 GHDGFPGKDGTGIKTT--TITYAGSTSGT 1584 Score = 384 bits (977), Expect = e-105 Identities = 179/322 (55%), Positives = 222/322 (68%), Gaps = 7/322 (2%) Query: 421 IRLEGPKGDAGLPGAPGRDGVDGVPGKSGVGIADTAITYAVSVSGTQEPENGWSEQVPEL 480 + + G KGD G PG +G +G+ GK G GI TAITY S +GT P WS VP + Sbjct: 1311 VAMMGVKGDKG--- DPGNNGTNGIAGKDGKGIKATAITYQASPNGTTAPTGTWSASVPPV 1367 Query: 481 IKGRFLWTKTFWRYTDGSHETGYSVAYIGQDGNSGKDGIAGKDGVGIAATEVMYASSPSA 540 KG FLWT+T W YTD + ETGY+VAY+G +GN+G DG GKDG GI T + YA S S Sbj ct: 1368 AKGSFLWTRTIWTYTDNTTETGYAVAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGSTSG 1427 Query: 541 TEAPAGGWSTQVPTVPGGQYLWTRTRWRYTDQTDEIGYSVSRMGEQGPKGDAGR-- -DGI 597 T P GW++ VPTV G YLWT+T W YTD T E GYSV+ MG +G KGD G +GI Sbjct: 1428 TTPPNNGWTSTVPTVAEGNYLWTKTVWTYTDNTSETGYSVAMMGVKGDKGDPGNNGTNGI 1487 Query: 598 AGKNGIGLKSTSVSYGISPTDSAIP-GVWASQVPSLIKGQYLWTRTIWTYTDSTTETGYQ 656 AGK+G G+K+T+++Y SP + P G W++ VP + KG +LWTRTIWTYTD+TTETGY Sbjct: 1488 AGKDGKGIKATAITYQASPNGTTAPTGTWSASVPPVAKGSFLWTRTIWTYTDNTTETGYA 1547 Query: 657 KTYIPKDGNDGKNGIAGKDGVGIKSTTITYAGSTSGTVAPTSNWTSAIPNVQPGFFLWTK 716 Y+ +GN+G +G GKDG GIK+TTITYAGSTSGT P + WTS +P V G +LWTK Sbjct: 1548 VAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGSTSGTTPPNNGWTSTVPTVAEGNYLWTK 1607 Query: 717 TVWNYTDDTSETGYSVSKIGET 738 TVW YTD++ ETGYSV K+G T Sbjct: 1608 TVWAYTDNSFETGYSVGKMGNT 1629 Score = 201 bits (507), Expect = 2e-50 Identities = 121/297 (40%), Positives = 156/297 (51%), Gaps = 19/297 (6%) Query: 421 IRLEGPKGDAGLPGAPGRDGVDGVPGKSGVGIAfDTAITYAVSVSGTQEPENGWSEQVPEL 480 + + G KGD G PG +G +G+ GK G GI TAITY S +GT P WS VP + Sbjct: 1467 VAMMGVKGDKG--- DPGNNGTNGIAGKDGKGIKATAITYQASPNGTTAPTGTWSASVPPV 1523 Query: 481 IKGRFLWTKTFWRYTDGSHETGYSVAYIGQDGNSGKDGIAGKDGVGIAATEVMYASSPSA 540 KG FLWT+T W YTD + ETGY+VAY+G +GN+G DG GKDG GI T + YA S S Sbjct: 1524 AKGSFLWTRTIWTYTDNTTETGYAVAYMGTNGNNGHDGFPGKDGTGIKTTTITYAGSTSG 1583 Query: 541 TEAPAGGWSTQVPTVPGGQYLWTRTRWRYTDQTDEIGYSVSRMGEQGPKGDAGRDGIAGK 600 T P GW++ VPTV G YLWT+T W YTD + E GYSV +MG GP AG +G GK Sbjct: 1584 TTPPNNGWTSTVPTVAEGNYLWTKTVWAYTDNSFETGYSVGKMGNTGP--- AGSNGNPGK 1640 Query: 601 NGIGLKSTSVSYGISPTDSAIPGVWASQVPSLIKG-QYLWTRTIWTYTDSTTE--TGYQK 657 + T+ G++ S + + ++ G +Y W W + G Sbjct: 1641 VVSDTEPTTKFKGLTWKYSGVVDMPLGNGTKILAGTEYYWNGNNWALYEINAHNINGDNL 1700 Query: 658 TYIPKDGNDGK-NGIAGKDGVGIKSTTITYAGS-----TSGTVAPTSNWTSAIPNVQ 708 + DGK I G +GV + T T GS +S + T N T AI N Q Sbjct: 1701 SVTNGTFKDGKIESIWGSNGV---NGTTTIEGSHLQIHSSDSTTNTEN-TLAIDNRQ 1753 Query= sidll4823Ilanjdp1ORFOO2 Phage dpi ORF132386-3583511 (1149 letters) >dbjIBAA31888 (AB009866) orf 15 [bacteriophage phi PVL] Length = 694 Score = 280 bits (709), Expect = 3e-74 Identities = 157/465 (33%), Positives = 257/465 (54%), Gaps = 28/465 (6%) Query: 40 QIGSALTGLGKGLTTAVTLPLMGFAAASIKVGNEFQAQMSRVQAIAGATAEELGRMKTQA 99 +IG+++ +G+ +T VT P++ A + K G EF M +V+A +GAT EE +K +A Sbjct: 151 EIGNSMKNVGRNMTMYVTAPVVAGFAVAAKKGIEFDDSMRKVKATSGATGEEFEALKKKA 210 WO 00/32825 PCT/IB99/02040 400 Query: 100 IDLGAKTAFSAKEAAQGMENLASAGFQVNEIMDAMPGVLDLXXXXXXXXXXXXXXMASSL 159 ++GA T FSA ++A+ + +A AG+ ++M+ + GV+DL + L Sbjct: 211 REMGATTKFSASDSAEALNYMALAGWDSKQMMEGLSGVMDLAAASGEELGAVSDIVTDGL 270 Query: 160 RAFGLEANQAGHVADVFARAAADTNAETSDMAEAMKYVAPVAHSMGLSLEETAASIGIMA 219 AFGL+A +GH+ADV A+ ++ N + + EA KYVAPVA ++G ++E+T+ +IG+M+ Sbjct: 271 TAFGLKAKDSGHLADVLAQTSSKANTDVRGLGEAFKYVAPVAGALGYTIEDTSIAIGLMS 330 Query: 220 DAGIKGSQAGTTLRGALSRIAKPTKAMVKSMQELGVSFYDANGNMIPLREQIAQLKTATA 279 +AGIKG +AGT LR + ++ PT+AM M+ LG+S D+NG MIP+R+ + QL+ Sbjct: 331 NAGIKGEKAGTALRTMFTNLSSPTRAMGNEMERLGISITDSNGKMIPMRKLLDQLREKFK 390 Query: 280 GLTQEERNRHLVTLYGQNSLSGMLALLDAGPEKLDKMTNALVNSDGAAKEMAETMQDNLA 339 L+++++ T++G+ ++SG LA+..+A E K+T ++ +S GA+K MA+TM+ L Sbjct: 391 HLSKDQQASSAATIFGKEAMSGALAIINASDEDYQKLTKSIDSSTGASKRMADTMESGLG 450 Query: 340 SKIEQMGGAFESVAIIVQQILEPALAKIVGAITKVLEAFVNMSPIGQKMVVIFAGMVAAL 399 K+ + E +A+ + +EPAL IV A +KV+ + Q VV F VA L Sbjct: 451 GKLRTLRSQLEELALTIYDRIEPALKIIVSAFSKVVTWVTKLPTSIQLAVVGFGLFVAVL 510 Query: 400 GPLLLIAGM-------VMTTIVKLRIAIQFLGPAFMGTMGTIAGVIAIF------------ 441 GPL+ + G+ MT + L I + F IA ++ +F Sbjct: 511 GPLVFMFGLFISVMGNAMTVLGPLLINVNKASGLFAFLRTKIASLVKLFPILGVSISSLT 570 Query: 442 -------YALVAV---FMIAYTKSERFRNFINSLAPAIKAGFGGA 476 ALV + F AY +SE FRN +N + F A Sbjct: 571 LPITLIVGALVGIGIAFYQAYKRSETFRNIVNQAISGVANAFKAA 615 Query= sid|114824Ilanjdp1ORFOO3 Phage dpl ORF153538-5587713 (779 letters) >spIP43741IDPO1_HAEIN DNA POLYMERASE I (POL I) >gill074025|pir||E64098 DNA polymerase I (polA) homolog - Haemophilus influenzae (strain Rd KW20) >gij1573871 (U32767) DNA polymerase I (polA) [Haemophilus influenzae Rd] Length = 930 Score = 191 bits (481), Expect = le-47 Identities = 148/553 (26%), Positives = 262/553 (46%), Gaps = 60/553 (10%) Query: 63 RLELITEEAKLEQYVDKMIEDGIGSIDVETDGLDTIHDELAGVCLYSPSQKGIYAPVNHV 122 + E + +A L ++++K+ + ++D ETD LD + L G+ + + Y P+ Sbjct: 333 KYETLLTQADLTRWIEKLNAAKLIAVDTETDSLDYMSANLVGISFALENGEAAYLPLQLD 392 Query: 123 SNMTKMRIKNQISPEFMKKMLQRIVDSGIPVIYHNSKFDMKSIYWRLGVKMNEPAWDTYL 182 ++ + +K +L+ + I I N KFD +SI+ R G+++ +DT L Sbjct: 393 YLDAPKTLEKSTALAAIKPILE ---NPNIHKIGQNIKFD-ESIFARHGIELQGVEFDTML 448 Query: 183 AAMLLNENESHSLKSLHSKYVRNEENAEVAKFNDLFKGIPFSLIPPDVAYMYAAYDPLQT 242 + LN H++ L +Y+ +E A + + F+ IP + A YAA D T Sbjct: 449 LSYTLNSTGRHNMDDLAKRYLGHETIAFESLAGKGKSQLTFNQIPLEQATEYAAEDADVT 508 Query: 243 FELYEFQEQYLTPGTEQCEEYNLEKVSWVLHNIEMPLIKVLFDMEVYGVDLDQDKLAEIR 302 +L + L E Y +E+PL+ VL ME GV +D D L Sbjct: 509 MKLQQALWLKLQEEPTLVELYK---------TMELPLLHVLSRMERTGVLIDSDALFMQS 559 Query: 303 EQFTANMNEAEQEFQQLVSEWQPEIEELRQTNFQSYQKLEMDARGRVTVSISSPTQLAIL 362 + + + E++ L + +++S QL + Sbjct: 560 NEIASRLTALEKQAYALAGQ---------------------------PFNLASTKQLQEI 592 Query: 363 FYDIMGLKSPERDKPRG---TGESIVEH--FDNDISXXXXXXXXXXXXVSTYTT-LDQHL 416 +D + L ++ P+G T E ++E + +++ STYT L Q + Sbjct: 593 LFDKLELPVLQKT-PKGAPSTNEEVLEELSYSHELPKILVKHRGLSKLKSTYTDKLPQMV 651 Query: 417 AKPDNRIHTTFKQYGAKTGRMSSENPNLQNIPSRGE-GAVVRQIFAASEGHYIIGSDYSQ 475 R+HT++ Q TGR+SS +PNLQNIP R E G +RQ F A EG+ I+ +DYSQ Sbjct: 652 NSQTGRVHTSYHQAVTATGRLSSSDPNLQNIPIRNEEGRHIRQAFIAREGYSIVAADYSQ 711 Query: 476 QEPRSLAELSGDESMRHAYEQNLDLYSVIGSKLYGVPYEECLEFYPDGTTNKEGKLRRNS 535 E R +A LSGD+ + +A+ Q D++ ++++GV +E T+++ R + Sbjct: 712 IELRIMAHLSGDQGLINAFSQGKDIHRSTAAEIFGVSLDE--------VTSEQ----RRN 759 Query: 536 VKSVLLGLMYGRGANSIAEQMNVSVKEANKVIEDFFTEFPKVADYIIFVQQQAQDLGYVQ 595 K++ GL+YG A ++ Q+ +S +A K ++ +F +P V ++ ++++A+ GYV+ WO 00/32825 PCT/IB99/02040 401 Sbjct: 760 AKAINFGLIYGMSAFGLSRQLGISRADAQKYMDLYFQRYPSVQQFMTDIREKAKAQGYVE 819 Query: 596 TATGRRRRLPDMS 608 T GRR LPD++ Sbjct: 820 TLFGRRLYLPDIN 832 Score = 46.9 bits (109), Expect = Se-04 Identities = 34/123 (27%), Positives = 66/123 (53%), Gaps = 16/123 (13%) Query: 663 EIKDQAKAEGI-------------LIKDNGGKIADAQRQCLNSVIQGTAADMTKYAMIKV 709 +I+++AKA+G + N + A+R +N+ +QGTAAD+ K AMIK+ Sbjct: 807 DIREKAKAQGYVETLFGRRLYLPDINSSNAMRRKGAERVAINAPMQGTAADIIKRAMIKL 866 Query: 710 HNDAELKELGFHLMIPVHDELLGEVPIKNAKRGAERLTEVMIEAAKDIISLPMKCDPSIV 769 ++ + +++ VHDEL+ EV + E++ + M EAA +++ +P+ + + Sbjct: 867 -DEVIRHDPDIEMIMQVHDELVFEVRSEKVAFFREQIKQHM-EAAAELV-VPLIVEVGVG 923 Query: 770 ERW 772 + W Sbjct: 924 QNW 926 Query= sid|1l4825Ilanidp1ORFOO4 Phage dpl ORF140401-4244013 (679 letters) >embICABO7981| (Z93946) hypothetical protein [bacteriophage Dp-1] Length = 532 Score = 1011 bits (2585), Expect = 0.0 Identities = 497/499 (99%), Positives = 498/499 (99%) Query: 1 MTKFINSYGPLHLNLYVEQVSQDVTNNSSRVSWRATVDRDGAYRTWTYGNISNLSVWLNG 60 MTKFINSYGPLHLNLYVEQVSQDVTNNSSRVSWRATVDRDGAYRTWTYGNISNLSVWLNG Sbjct: 1 MTKFINSYGPLHLNLYVEQVSQDVTNNSSRVSWRATVDRDGAYRTWTYGNISNLSVWLNG 60 Query: 61 SSVHSSHPDYDTSGEEVTLASGEVTVPHNSDGTKTMSVWASFDPNNGVHGNITISTNYTL 120 SSVHSSHPDYDTSGEEVTLASGEVTVPHNSDGTKTMSVWASFDPNNGVHGNITISTNYTL Sbjct: 61 SSVHSSHPDYDTSGEEVTLASGEVTVPHNSDGTKTMSVWASFDPNNGVHGNITISTNYTL 120 Query: 121 DSIPRSTQISSFEGNRNLGSLHTVIFNRKVNSFTHQVWYRVFGSDWIDLGKNHTTSVSFT 180 DSIPRSTQISSFEGNRNLGSLHTVIFNRKVNSFTHQVWYRVFGSDWIDLGKNHTTSVSFT Sbjct: 121 DSIPRSTQISSFEGNRNLGSLHTVIFNRKVNSFTHQVWYRVFGSDWIDLGKNHTTSVSFT 180 Query: 181 PSLDLARYLPKSSSGTMDICIRTYNGTTQIGSDVYSNGWRFNIPDSVRPTFSGISLVDTT 240 PSLDLARYLPKSSSGTMDICIRTYNGTTQIGSDVYSNGWRFNIPDSVRPTFSGISLVDTT Sbjct: 181 PSLDLARYLPKSSSGTMDICIRTYNGTTQIGSDVYSNGWRFNIPDSVRPTFSGISLVDTT 240 Query: 241 SAVRQILTGNNFLQIMSNIQVNFNNASGAYGSTIQAFHAELVGKNQAINENGGKLGMMNF 300 SAVRQILTGNNFLQIMSNIQVNFNNASGAYGSTIQAFHAELVGKNQAINENGGKLGMMNF Sbjct: 241 SAVRQILTGNNFLQIMSNIQVNFNNASGAYGSTIQAFHAELVGKNQAINENGGKLGMMNF 300 Query: 301 NGSATVRAWVTDTRGKQSNVQDVSINVIEYYGPSINFSVQRTRQNPAIIQALRNAKVAPI 360 NGSATVRAWVTDTRGKQSNVQDVSINVIEYYGPSINFSVQRTRQNPAIIQALRNAKVAPI Sbjct: 301 NGSATVRAWVTDTRGKQSNVQDVSINVIEYYGPSINFSVQRTRQNPAIIQALRNAKVAPI 360 Query: 361 TVGGQQKNIMQITFSVAPLNTTNFTEDRGSASGTFTTISLMTNSSANLAGNYGPDKSYIV 420 TVGGQQKNIMQITFSVAPLNTTNFTEDRGSASGTFTTISL+TNSSANLAGNYGPDKSYIV Sbjct: 361 TVGGQQKNIMQITFSVAPLNTTNFTEDRGSASGTFTTISLLTNSSANLAGNYGPDKSYIV 420 Query: 421 KAKIQDRFTSTEFSATVATESVVLNYDKDGRLGVGKVVEQGKAGSIDAAGDIYAGGRQVQ 480 KAKIQDRFTSTEFSATV TESVVLNYDKDGRLGVGKVVEQGKAGSIDAAGDIYAGGRQVQ Sbjct: 421 KAKIQDRFTSTEFSATVPTESVVLNYDKDGRLGVGKVVEQGKAGSIDAAGDIYAGGRQVQ 480 Query: 481 QFQLTDNNGALNRGQYNDV 499 QFQLTDNNGALNRGQYNDV Sbjct: 481 QFQLTDNNGALNRGQYNDV 499 Query= sid|1l4827|lanjdp1ORFOO6 Phage dpi ORF145296-4698712 (563 letters) >gblAAD18987| (AE001666) SWI/SNF family helicase_2 [Chlamydia pneumoniae] Length = 1166 Score = 171 bits (429) , Expect = le-41 Identities = 150/522 (28%), Positives = 254/522 (47%), Gaps = 55/522 (10%) WO 00/32825 PCT/IB99/02040 402 Query: 46 SSNNFE-LPYKYFNNVIDALDEWELHIFGELDKDVQDYIDSRNRIASSSNEQFSFKTTPF 104 S + FE LP + ++ + L E + I GE++ D QD + T Sbjct: 659 SLDQFEALPVNF--SMSERLIEIQKQIRGEIEFDFQD-------VPQQIQATLRSYQTEG 709 Query: 105 AHQVECFEYAQEHPCFLLGDEQGLGKTKQAIDIAVSRKASFKH--CLIVCCISGLKWNWA 162 H +E + H +L D+ GLGKT QAI IAV++ K C ++ C + L +NW Sbjct: 710 VHWLE--RLRKMHLNGILADDMGLGKTLQAI-IAVTQSKLEKGSGCSLIVCPTSLVYNWK 766 Query: 163 KEVGIHSNESAHILGSRVTKDGKLVIDGV-SKRAEDLLGGHDEFFLITNIETLRDAVFIK 221 +E + E LVIDGV S+R + L D IT+ L+ V Sbjct: 767 EEFRKFNPEFR-----------TLVIDGVPSQRRKQLTALADRDVAITSYNLLQKDV--- 812 Query: 222 YLNELTKSGEIGMVIIDEIHKCKNPSSKQGASIQKLQSYYKMGLTGTPLMNNPIDVFNVM 281 EL KS V++DE H KN +++ S++ +QS +++ LTGTP+ N+ +++++ Sbjct: 813 ---ELYKSFRFDYVVLDEAHHIKNRTTRNAKSVKMIQSDHRLILTGTPIENSLEELWSLF 869 Query: 282 KWLGAEHHTLTQFKERYCIVDQFNQITGYR-----NLAELRELVNDYMLRRTKEEVL-DL 335 +L L +R+ V ++ + Y N+ L++ V+ ++LRR KE+VL DL Sbjct: 870 DFLMPG---LLSSYDRF--VGKYIRTGNYMGNKADNMVALKKKVSPFILRRMKEDVLKDL 924 Query: 336 PEKIRVTEYVDMNSKQSKIY-------KEVLTKLVQEIDKVKLMPNPLAETIRLRQATGN 388 P + + + Q ++Y K+ L++LV++ ++ + LA RL+Q + Sbjct: 925 PPVSEILYHCHLTESQKELYQSYAASAKQELSRLVKQEGFERIHIHVLATLTRLKQICCH 984 Query: 389 PSILTTQDVK---SCKFERCIEIVEECIQQGKSCVIFSNWEKVIEPLAKIL-SKTVKCNL 444 P+I + S K++ ++++ + G V+FS + K++ + K L S+ + Sbjct: 985 PAIFAKDAPEPGDSAKYDMLMDLLSSLVDSGHKTVVFSQYTKMLGIIKKDLESRGIPFVY 1044 Query: 445 VTGETADKFNEIEEFMNHRKASVILGTIGALGTGFTLTKADTVIFLDSPWTRAEKDQAED 504 + G T ++ + + +F V L ++ A GTG L ADTVI D W A ++QA D Sbjct: 1045 LDGSTKNRLDLVNQFNEDPSLLVFLISLKAGGTGLNLVGADTVIHYDMWWNPAVENQATD 1104 Query: 505 RCHRIGAKSSVTIYTLVAKGTVDERIEDLIERKGELADYIVD 546 R HRIG SV+ Y LV T++E+I L RK L +++ Sbjct: 1105 RVHRIGQSRSVSSYKLVTLNTIEEKILTLQNRKKSLVKKVIN 1146 Query= sidI14828IlanidploRFO07 Phage dpi ORF122230-2362113 (463 letters) >gil2444105 (U88974) ORF26 [Streptococcus thermophilus temperate bacteriophage 01205] Length = 411 Score = 88.9 bits (217), Expect = 7e-17 Identities = 80/315 (25%), Positives = 133/315 (41%), Gaps = 48/315 (15%) Query: 139 QGVTLAGIFCDEVALMPESFVNQATGRCSVTGSKMWFSCNPANPNHYFKKNWIDKQVEKR 198 +G T G + +E +L E + RCS G+++ + NP NPNH+ +++I K + + Sbjct: 121 RGFTAFGAYVNEASLANELVFKEIISRCSGDGARVVWDSNPDNPNHWLNRDYIGKN-DGK 179 Query: 199 ILYLHFTMDDNPSLT ---- DSIKRRYEKMYAGVFRKRFILGLWVTADGLVYSMFNEEQHV 254 I+ F +DDN L+ DSIK K G F R ILGLW A+G +Y+ ++ + HV Sbjct: 180 IIDFSFKLDDNTFLSKRYIDSIKAATPK--- GKFYDRDILGLWTVAEGAIYADYDSKIHV 236 Query: 255 KKLNIEFDRLFVAGDFGIYNATTFGLYGFSKRHKRYHLIESYYHSGREAEEQLTEADVNS 314 E R F D+G + + + G ++L++ +E + + +A Sbjct: 237 VDELPEMKRYFGGIDWGYTHYGSIVIVG-EGVDNNFYLVDGVAAQFKEIDWWVEQA---- 291 Query: 315 NIQFSSVLQKTTKEYANDLVDMIRGKQIEYIILDPSASAMIVELQKHPYIAR--- KNIPI 371 +K T Y N + + ++AR + I Sbjct: 292 -------- RKLTGIYGN---------------------IPFYADSARPEHVARFENEGFDI 323 Query: 372 IPARNDVTLGISFHAELLAENRFTLDPSNT-HDIDEYYAYSWDSKASQTGEDRVIKEHDH 430 + A V GI A+L E + + DE Y Y W ++ +D +KE D Sbjct: 324 MNANKSVIAGIELIAKLFKEKKLYVKRGFVPRFFDEIYQYRWKENST---KDEPLKEFDD 380 Query: 431 CMDRNRYACLTDALI 445 +D RYA +D +I Sbjct: 381 VLDSVRYAIYSDYVI 395 Query= sid114829IlanIdp1ORFOO8 Phage dpl ORF149624-5096111 (445 letters) >gblAAD19901| (AF100420) DnaB replication fork helicase [Thermus aquaticus] WO 00/32825 PCT/IB99/02040 403 Length = 444 Score = 67.5 bits (162), Expect = 2e-10 Identities = 69/248 (27%), Positives = 111/248 (43%), Gaps = 14/248 (5%) Query: 147 GERLGISTGFEXXXXXXXXXXXXXXXIVIMARPGQGKS-WTIDKMLATAWKNGHDVLLYS 205 GE G+ TGF+ I I ARP GK++ + A K G V +YS Sbjct: 178 GEVAGVRTGFKELDQLIGTLGPGSLNI-IAARPAMGKTAFALTIAQNAALKEGVGVGIYS 236 Query: 206 GEMSEMQVGARIDTILSNVSINSITKGIWNDHQFEKYEDHIQAMTEAENSLVVVTPFMIG 265 EM Q+ R+ + ++N + G D F + D ++EA + TP + Sbjct: 237 LEMPAAQLTLRMMCSEARIDMNRVRLGQLTDRDFSRLVDVASRLSEAP-IYIDDTPDLTL 295 Query: 266 GKNLTPAILDSMISKYRPSVVGIDQLSLMS--ESYPSREQKRIQYANITMDLYKISAKYG 323 + A ++S+ + ++ ID L LMS S S E ++ + A I+ L ++ + G Sbjct: 296 ME--VRARARRLVSQNQVGLIIIDYLQLMSGPGSGKSGENRQQEIAAISRGLKALARELG 353 Query: 324 IPIVLNVQAGRSAKTEGAESMELEHIAESDGVGQNASRVIAMKRD-------EKSGILEL 376 IPI+ Q R+ + + L + ES + Q+A V+ + RD EK+GI E+ Sbjct: 354 IPIIALSQLSRAVEARPNKRPMLSDLRESGSIEQDADLVMFIYRDEYYNPHSEKAGIAEI 413 Query: 377 SVVKNRYG 384 V K R G Sbjct: 414 IVGKQRNG 421 Query= sidll4831|1anIdplORF010 Phage dpl ORF18699-985912 (386 letters) >gil2760912 (AF037258) RecA protein (Chlorobium tepidum] Length = 346 Score = 133 bits (331), Expect = 2e-30 Identities = 99/340 (29%), Positives = 164/340 (48%), Gaps = 66/340 (19%) Query: 44 GGLPRKRVVEFFGPESSGKTTSALDIVKNAQMVFXXXXXXXXXXXXXXXXNARASKASKT 103 GGLPR RV E +GPESSGKTT AL + AQ Sbjct: 67 GGLPRGRVTEIYGPESSGKTTLALHAIAEAQ--------------------------KNG 100 Query: 104 AVKELEMQLDSLQEPLKIVYLDLENTLDTEWAKKIGVDVDNIWIVRPEMNSAEEILQYVL 163 + L +D E+ D +A+K+GVD++ + + +PE S E+ L V Sbjct: 101 GIAAL----------------VDAEHAFDPTYARKLGVDINALLVSQPE--SGEQALSIVE 143 Query: 164 DIFETGEVGLVVLDSLPYMVSQNLIDEELTKKAYAGISAPLTEFSRKVTPLLTRYNAIFL 223 + +G V ++V+DS+ +V Q ++ E+ + +++ RK+T +++ +++ L Sbjct: 144 TLVRSGAVDIIVIDSVAALVPQAELEGEMGDSVVGLQARLMSQALRKLTGAISKSSSVCL 203 Query: 224 GINQIREDMNSQYNA-YSTPGGKMWKHACAVRLKFRKGDYLDENGASLTRTARNPAGNVV 282 INQ+R+ + Y + +T GGK K +VRL RK + ++G L GN Sbjct: 204 FINQLRDKIGVMYGSPETTTGGKALKFYSSVRLDIRKIAQI-KDGEELV-------GNRT 255 Query: 283 ESFVEKTKAFKPDRKLVSYTLSYHDGIQIENDLVDVAVEFGVIQKAGAWFSIVDLETGEI 342 + V K K P K + + Y +GI + +L+D+AVEFG+I+K+GAWFS + G Sbjct: 256 KVKVVKNKV-APPFKTAEFDILYGEGISVLGELIDLAVEFGIIKKSGAWFSYGTEKLG-- 312 Query: 343 MTDEDEEPLKFQGKANLVRRFKEDDYLFDMVMTAVHEIIT 382 QG+ N+ + KED+ L + + V +++T Sbjct: 313 ----------- QGRENVKKLLKEDETLRNTIRQQVRDMLT 341 Query= sidI1148321anldplORFOl1 Phage dpi ORF128017-29096[3 (359 letters) >gil2444110 (U88974) ORF31 (Streptococcus thermophilus temperate bacteriophage 01205] Length = 348 Score = 187 bits (469), Expect = le-46 Identities = 118/358 (32%), Positives = 187/358 (51%), Gaps = 21/358 (5%) Query: 3 IYDYINAGEIASYIQALPSNALQYLGPTLFPNAQQTGTDISWLKGANNLPVTIQPSNYDA 62 IYD + A IA Y AL N LG ++FP +Q GT +S++KGA+ V ++ + +D Sbjct: 4 IYDKVTASNIAGYFNALQENVSSTLGESIFPARKQLGTKLSYIKGASGQSVALKAAAFDT 63 Query: 63 KASLRERAGFSKQATEMAFFRESMRLGEKDRQNLQMLLNQSSA-LAQPLITQLYNDTKNL 121 WO 00/32825 PCT/IB99/02040 404 ++R+R +M FF+E+M + E DRQ L ++ + +A L ++ ++ND L Sbjct: 64 NVTIRDRVSAEMHDEQMPFFKEAMLVKENDRQQLNLVKDSGNAVLVNTIVAGIFNDNLTL 123 Query: 122 VDGVEAQAEYMRMQLLQYGKFTVKSTNSEAQYTYDYNMDAKQQYAVTKKWTNPAESDPIA 181 V+G A+ E MRMQ+L GK S Y D K+Q V+K W P + P+A Sbjct: 124 VNGARARLEAMRMQVLATGKIAFTSDGVNKDIDYGVKPDHKKQ--VSKSWAEPG-ATPLA 180 Query: 182 DILAAMDDIENRTGVRPTRMVLNRNTYNQMTKSDSIKKAL-AIGVQGSWENFLLLASDAE 240 D+ A+ + G+ P R V+N T+ + K+ S K + + GS + ++ E Sbjct: 181 DLEDAI-ETARELGLNPERAVMNAKTFGLIRKAASTVKVIKPLAGDGS----AVTKAELE 235 Query: 241 KFIAEKTGLQIAVYSKKIAQFADADKLPDVGNIRQFNLIDDGKVVLLPPDAVGHTWYGTT 300 +IA+ G+ I + + D G + +F DG + L+P +G+T +GTT Sbjct: 236 NYIADNFGVSIVLENGTYRN--------DKGEVSKF--YPDGHLTLIPNGPLGNTVFGTT 285 Query: 301 PEAFDLASGGT-DAQVQVLSGGPTVTTYLEKHPVNIATVVSAVMIPSFEGIDYVGVLT 357 PE DL + T +A+V+++ G VTT PVN+ T VS V +PSFE +D V +LT Sbjct: 286 PEESDLFADNTVNAEVEIVDNGIAVTTTKTTDPVNVQTKVSMVALPSFERLDDVYMLT 343 Query= sidl11483411anldp10RF013 Phage dpi ORF110215-1124013 (341 letters) >spIP09122IDP3XBACSU DNA POLYMERASE III SUBUNITS GAMMA AND TAU Length = 563 Score = 182 bits (458), Expect = 2e-45 Identities = 118/353 (33%), Positives = 176/353 (49%), Gaps = 31/353 (8%) Query: 7 YRPQTFEEVVAQEYVKEILLNQLQNGAIKHGYLFCXXXXXXXXXXXRIFAKDVN------ 60 +RPQ FE+VV QE++ + L N L H YLF +IFAK VN Sbjct: 10 FRPQRFEDVVGQEHITKTLQNALLQKKFSHAYLFSGPRGTGKTSAAKIFAKAVNCEHAPV 69 Query: 61 ---------- KGL ----- GSPIEIDAASNNGVENVRNIIEDSRYKSMDSEFKVYIIDEVH 105 KG+ IEIDAASNNGV+ +R+I + ++ +KVYIIDEVH Sbjct: 70 DEPCNECAACKGITNGSISDVIEIDAASNNGVDEIRDIRDKVKFAPSAVTYKVYIIDEVH 129 Query: 106 MLSTGAFNALLKTLEEPSSGTVFILCTTDPQKIPDTILSRVQRFDFTRIDNDDIVNQLQF 165 MLS GAFNALLKTLEEP +FIL TT+P KIP TI+SR QRFDF RI + IV ++ Sbjct: 130 MLSIGAFNALLKTLEEPPEHCIFILATTEPHKIPLTIISRCQRFDFKRITSQAIVGRMNK 189 Query: 166 IIESENEEGAGYSYERDALSFIGKLANGGMRDSITRLEKVLDYSHHVDMEAVSNAL ---G 222 I+++. E E +L I A+GGMRD+++ L++ + +S D+ V +AL G Sbjct: 190 IVDAEQ-----LQVEEGSLEIIASAAHGGMRDALSLLDQAISFSG--DILKVEDALLITG 242 Query: 223 VPDYETFASLVEAIANYDGSKCLEIVNDFHYSGKDLKLVTRNFTDFLLEVCKYWLVRDIS 282 L +++ + + S LE +N+ GKD + + + ++ Y + Sbjct: 243 AVSQLYIGKLAKSLHDKNVSDALETLNELLQQGKDPAKLIEDMIFYFRDMLLYKTAPGLE 302 Query: 283 ITQLPAHFESKLEQFCEAFQYPTLLWMLEEMNELAGVVKWEPNAKPIIETKLL 335 + + E L M++ +N+ +KW + + E ++ Sbjct: 303 GVLEKVKVDETFRELSEQIPAQALYEMIDILNKSHQEMKWTNHPRIFFEVAVV 355 Query= sidll4835|lanldplORF014 Phage dpl ORF150961-5197413 (337 letters) >spIP47492IPRIMMYCGE DNA PRIMASE >gi|1361496|pir| |F64227 DNA primase (dnaE) homolog MG250 - Mycoplasma genitalium (SGC3) >gij3844848 (U39704) DNA primase (dnaE) [Mycoplasma genitalium] Length = 607 Score = 57.0 bits (135), Expect = 2e-07 Identities = 53/190 (27%), Positives = 89/190 (45%), Gaps = 17/190 (8%) Query: 146 EELDKYRFIHP-------YMYERKLTDELIEMFDVGYDK--LHDCITFPVRNLKGETVFF 196 E +++Y FI+P Y++ K + + FD K + I P+ + G V F Sbjct: 170 ESMERYPFINPKIKPSELYLFS-KTNQQGLGFFDFNTKKATFQNQIMIPIHDFNGNPVGF 228 Query: 197 NRRSVRSKFHQYGEDDPKTEFLYGQYELVAFRDYFEKPISQVFVTESVINCLTLWSMKIP 256 + RSV + ++ EF + + EL+ K ++Q+F+ E + TL + K Sbjct: 229 SARSVDNINKLKYKNSADHEF-FKKGELLFNFHRLNKNLNQLFIVEGYFDVFTLTNSKFE 287 Query: 257 AVALMGVGGGN-QINLLKR--LPYRNIVLALDPDNAGQTAQEKLYRQLKRSK-VVRFLNY 312 AVALMG+ + QI +K + +VLALD D +GQ A L +L + +V + + Sbjct: 288 AVALMGLALNDVQIKAIKAHFKELQTLVLALDNDASGQNAVFSLIEKLNNNNFIVEIVQW 347 WO 00/32825 PCT/IB99/02040 405 Query: 313 PKEFYDNKWD 322 + D WD Sbjct: 348 EHNYKD--WD 355 Query= sidll14837|1anldplORF016 Phage dpi ORF143413-4430313 (296 letters) >embICABo7986I (Z93946) N-acetylmuramoyl-L-alanine amidase (bacteriophage Dp-1] Length = 296 Score = 661 bits (1686), Expect = 0.0 Identities = 296/296 (100%), Positives = 296/296 (100%) Query: 1 MGVDIEKGVAWMQARKGRVSYSMDFRDGPDSYDCSSSMYYALRSAGASSAGWAVNTEYMH 60 MGVDIEKGVAWMQARKGRVSYSMDFRDGPDSYDCSSSMYYALRSAGASSAGWAVNTEYMH Sbj ct: 1 MGVDIEKGVAWMQARKGRVSYSMDFRDGPDSYDCSSSMYYALRSAGASSAGWAVNTEYMH 60 Query: 61 AWLIENGYELISENAPWDAKRGDIFIWGRKGASAGAGGHTGMFIDSDNIIHCNYAYDGIS 120 AWLIENGYELISENAPWDAKRGDIFIWGRKGASAGAGGHTGMFIDSDNI IHCNYAYDGIS Sbjct: 61 AWLIENGYELISENAPWDAKRGDIFIWGRKGASAGAGGHTGMFIDSDNIIHCNYAYDGIS 120 Query: 121 VNDHDERWYYAGQPYYYVYRLTNANAQPAEKKLGWQKDATGFWYARANGTYPKDEFEYIE 180 VNDHDERWYYAGQPYYYVYRLTNANAQPAEKKLGWQKDATGFWYARANGTYPKDEFEYIE Sbjct: 121 VNDHDERWYYAGQPYYYVYRLTNANAQPAEKKLGWQKDATGFWYARANGTYPKDEFEYIE 180 Query: 181 ENKSWFYFDDQGYMLAEKWLKHTDGNWYWFDRDGYMATSWKRIGESWYYFNRDGSMVTGW 240 ENKSWFYFDDQGYMLAEKWLKHTDGNWYWFDRDGYMATSWKRIGESWYYFNRDGSMVTGW Sbjct: 181 ENKSWFYFDDQGYMLAEKWLKHTDGNWYWFDRDGYMATSWKRIGESWYYFNRDGSMVTGW 240 Query: 241 IKYYDNWYYCDATNGDMKSNAFIRYNDGWYLLLPDGRLADKPQFTVEPDGLITAKV 296 IKYYDNWYYCDATNGDMKSNAFIRYNDGWYLLLPDGRLADKPQFTVEPDGLITAKV Sbjct: 241 IKYYDNWYYCDATNGDMKSNAFIRYNDGWYLLLPDGRLADKPQFTVEPDGLITAKV 296 Query= sidI114841lanldp1oRF020 Phage dpi ORF11864-265811 (264 letters) >embICAB13247I (Z99111) similar to coenzyme PQQ synthesis (Bacillus subtilis] Length = 243 Score = 217 bits (548), Expect = Se-56 Identities = 117/248 (47%), Positives = 163/248 (65%), Gaps = 15/248 (6%) Query: 23 MPIMEIFGPTIQGEGMVIGQKTIFIRTGGCDYHCNWCDSAFTWNGTTEPE--YITGKEAA 80 +P++EIFGPTIQGEGMVIGQKT+F+RT GCDY C+WCDSAFTW+G+ + + ++T +E Sbjct: 5 IPVLEIFGPTIQGEGMVIGQKTMFVRTAGCDYSCSWCDSAFTWDGSAKKDIRWMTAEEIF 64 Query: 81 SRILKLAFNDKGEQICNHVTLTGGNPALINEPMAKMISILKEHGFKFGLETQGTRFQEWF 140 + + D G +HVT++GGNPAL+ ++ I +LKE+ + LETQGT +Q+WF Sbjct: 65 AEL-----KDIGGDAFSHVTISGGNPALLKQ-LDAFIELLKENNIRAALETQGTVYQDWF 118 Query: 141 KEVSDITISPKPPSSGMRTNMKILEAIVDRM--NDENLDWSFKIVIFDENDLAYARDMFK 198 + D+TISPKPPSS M TN + L+ I+ + ND S K+VIF++ DL +A+ + K Sbjct: 119 TLIDDLTISPKPPSSKMVTNFQKLDHILTSLQENDRQHAVSLKVVIFNDEDLEFAKTVHK 178 Query: 199 TFEGKLRPVNYLSVGNANAY--EEGKISDRLLEKLGWLWDKVYEDPAFNNVRPLPQLHTL 256 + G YL VGN + + ++ + LL K L DKV D N VR LPQLHTL Sbjct: 179 RYPG--- IPFYLQVGNDDVHTTDDQSLIAHLLGKYEALVDKVAVDAELNLVRVLPQLHTL 235 Query: 257 VYDNKRGV 264 ++ NKRGV Sbjct: 236 LWGNKRGV 243 WO 00/32825 PCT/IB99/02040 406 Query= sidI114842IlanIdp1ORF021 Phage dpl ORF12504-329512 (263 letters) >spIP19465IGCH1_BACSU GTP CYCLOHYDROLASE I (GTP-CH-I) >giI98411|pir|IA38256 GTP cyclohydrolase I (EC 3.5.4.16) - Bacillus subtilis >gi1143231 (M37320) regulatory protein (Bacillus subtilis] >giJ143799 (M80245) MtrA (Bacillus subtilis] >gil2634696|emb|CAB14194| (Z99115) GTP cyclohydrolase I (Bacillus subtilis] Length = 190 Score = 208 bits (523), Expect = 4e-53 Identities = 103/185 (55%), Positives = 133/185 (71%), Gaps = 1/185 (0%) Query: 80 VTLDNTEAAVQRLFGLLGEDAERDGLQDTPFRFVKALAEHTVGYREDPKLHLEKTFDVDH 139 V + E AV+++ +GED R+GL DTP R K AE G EDPK H + F +H Sbjct: 4 VNKEQIEQAVRQILEAIGEDPNREGLLDTPKRVAKMYAEVFSGLNEDPKEHFQTIFGENH 63 Query: 140 EDLVLVKDIPFNSLCEHHLAPFVGKVHIAYIPKD-KITGLSKFGRVVEGYAKRLQVQERL 198 E+LVLVKDI F+S+CEHHL PF GK H+AYIP+ K+TGLSK R VE AKR Q+QER+ Sbjct: 64 EELVLVKDIAFHSMCEHHLVPFYGKAHVAYIPRGGKVTGLSKLARAVEAVAKRPQLQERI 123 Query: 199 TQQIADAIQEVLNPQAVAVIVEAEHTCMSGRGIKKHGATTVTSTMRGLFQDDASARAELL 258 T IA++I E L+P V V+VEAEH CM+ RG++K GA TVTS +RG+F+DDA+ARAE+L Sbj ct: 124 TSTIAESIVETLDPHGVMVVVEAEHMCMTMRGVRKPGAKTVTSAVRGVFKDDAAARAEVL 183 Query: 259 QLIKK 263 + IK+ Sbjct: 184 EHIKR 188 Query= sidll14843IlanIdplORF022 Phage dpl ORF130896-3167512 (259 letters) >gil2347102 (U77367) internalin [Listeria monocytogenes] Length = 821 Score = 55.0 bits (130), Expect = 5e-07 Identities = 44/149 (29%), Positives = 63/149 (41%), Gaps = 13/149 (8%) Query: 119 FRMNIYVPNYVG--DSIVNYVKITLNNCTGKAPGLSIGKEFYAPEFNIKAREATKAGLPV 176 F + VPN + D + + NN T AP L Y PE +K + K + Sbjct: 383 FSKTLSVPNNITSIDGTLIAPETISNNGTYDAPNLKWSLPNYLPE--VKYTFSQKIPIGT 440 Query: 177 KSMDYVAQLPAVLR-----RVTFDLNGGTGTADAVRVEAGKKISPKPVDPTLTGKAFKGW 231 + +Y + L+ +VTF++ G T + V E + P+P PT G F GW Sbjct: 441 GTSNYSGFITQPLKELLDYKVTFNVEGNTSEVETVTEE---NLIPEPTSPTKQGYTFDGW 497 Query: 232 -KVEGESTIWDFDNHMMPDRDVKLVAQFA 259 E T WDF MP D+ L A F+ Sbjct: 498 YDAETGGTKWDFTTGQMPANDLTLYAHFS 526 Score = 43.4 bits (100), Expect = 0.002 Identities = 47/195 (24%), Positives = 73/195 (37%), Gaps = 12/195 (6%) Query: 72 YDLTFKDNTFDPEIMALIEGGTVRQQGGTIAGYDT-PMLAQGASNMKPFRMNIYVPNY-- 128 YD + T + +G + GG + T M A + F +N Y N+ Sbjct: 547 YDALLNEPTTPTKQGYTFDGWYDAETGGNKWDFKTMKMPANDVAFYAHFTINNYQANFDI 606 Query: 129 --- VGDSIVNYVKITLNNCTGKAPGLSIGKEFYAPEFNIKAREATKAGLPVKSMDYVAQL 185 V + + Y + T G + + A K TK +P + A Sbjct: 607 DGEVKNETIAYDTLLNEPTTPTKQGYTFDGWYDAETGGTKWDFKTKE-MPANDVTLYAHF 665 Query: 186 PAVLRRVTFDLNGGTGTADAVRVEAGKKISPKPVDPTLTGKAFKGW-KVEGESTIWDFDN 244 + FD++G T + V +A + P+P P+ TG +GW E T WDF Sbjct: 666 TINNYQANFDIDGAV-TEEVVNYDA---LIPEPTSPSKTGFTLEGWYDAEVGGTKWDFKT 721 Query: 245 HMMPDRDVKLVAQFA 259 MP D+ L A F+ Sbjct: 722 MKMPANDITLYAHFS 736 Score = 38.3 bits (87), Expect = 0.057 Identities = 42/169 (24%), Positives = 59/169 (34%), Gaps = 10/169 (5%) WO 00/32825 PCT/IB99/02040 407 Query: 96 QQGGTIAGYDT-PMLAQGASNMKPFRMNIYVPNYVGDSIVNYVKIT ---- LNNCTGKAPG 150 + GGT + T M A + F +N Y N+ D +V + LN T Sbjct: 501 ETGGTKWDFTTGQMPANDLTLYAHFSVNSYQANFDIDGVVTNEAVVYDALLNEPTTPTKQ 560 Query: 151 LSIGKEFYAPEFNIKAREATKAGLPVKSMDYVAQLPAVLRRVTFDLNGGTGTADAVRVEA 210 +Y E + +P + + A + FD++G A Sbjct: 561 GYTFDGWYDAETGGNKWDFKTMKMPANDVAFYAHFTINNYQANFDIDGEVKNETI ---- A 616 Query: 211 GKKISPKPVDPTLTGKAFKGW-KVEGESTIWDFDNHMMPDRDVKLVAQF 258 + +P PT G F GW E T WDF MP DV L A F Sbjct: 617 YDTLLNEPTTPTKQGYTFDGWYDAETGGTKWDFKTKEMPANDVTLYAHF 665 Query= sidF1l4850|lanidp1ORF029 Phage dpl ORF1662-134812 (228 letters) >gil2650185 (AE001074) succinoglycan biosynthesis regulator (exsB) [Archaeoglobus fulgidus] Length = 239 Score = 119 bits (295), Expect = 2e-26 Identities = 79/224 (35%), Positives = 113/224 (50%), Gaps = 11/224 (4%) Query: 1 MKSVVLLSGGVDSATCLAIEVDKWGSKNVHAIAFNYGQKHEAELENAANVAMFYGVKFTI 60 MK+V+LLSGG+DS+T L +D G VHA+ F YGQKH E+E+A VA V+ Sbjct: 1 MKAVMLLSGGIDSSTLLYYLLD--GGYEVHALTFFYGQKHSKEIESAEKVAKAAKVRHLK 58 Query: 61 LEIDSKIYXXXXXXLLQGKGEISHGKSYAEILAEKEVVDTYVPFRNGLMLSQXXXXXXXX 120 ++I S I+ L G+ E+ Y+E + + T VP RN ++LS Sbjct: 59 VDI-STIHDLISYGALTGEEEVPKA-FYSEEVQRR----TIVPNRNMILLS--IAAGYAV 110 Query: 121 XXXXXXXXXXXXXXXXXXXPDCTPEFYNSMSNAMEYGT-GGKVTLVAPLLTLTKAQVVKW 179 PDC EF ++ A+ V + AP + +TKA +V+ Sbjct: 111 KIGAKEVHYAAHLSDYSIYPDCRKEFVKALDTAVYLANIWTPVEVRAPFVDMTKADIVRL 170 Query: 180 GIDLDVPYFLTRSCYESDAESCGTCATCIDRKKAFEENGMTDPI 223 G+ L VPY LT SCYE C +C TC++R +AF NG+ DP+ Sbjct: 171 GLKLGVPYELTWSCYEGGDRPCLSCGTCLERTEAFLANGVKDPL 214 Query= sidI|14855|landplORF034 Phage dpl ORF|131-65212 (173 letters) >embICAB13248| (Z99111) similar to hypothetical proteins [Bacillus subtilis] Length = 165 Score = 220 bits (556), Expect = 4e-57 Identities = 103/139 (74%), Positives = 117/139 (84%) Query: 5 TTRTDAELTGVTLLGNQDTKYDYDYNPDVLETFPNKHPENNYLVTFDGYEFTSLCPKTGQ 64 TTR ++EL GVTLLGNQ T Y ++Y PDVLE+FPNKH +Y V F+ EFTSLCPKTGQ Sbjct: 2 TTRKESELEGVTLLGNQGTNYLFEYAPDVLESFPNKHVNRDYFVKFNCPEFTSLCPKTGQ 61 Query: 65 PDFANVFISYIPNEKMVESKSLKLYLFSFRNHGDFHEDCMNIILNDLYELMEPKYIEVMG 124 PDFA ++ISYIP+EKMVESKSLKLYLFSFRNHGDFHEDCMNII+NDL ELM+P+YIEV G Sbjct: 62 PDFATIYISYIPDEKMVESKSLKLYLFSFRNHGDFHEDCMNIIMNDLIELMDPRYIEVWG 121 Query: 125 LFTPRGGISIYPFVNKVNP 143 FTPRGGISI P+ N P Sbjct: 122 KFTPRGGISIDPYTNYGKP 140 Query= sidll4857|lanldplORF036 Phage dpl ORF148808-4936211 (184 letters) >gi|1353529 (U38906) ORF12 [Bacteriophage rit] Length = 296 Score = 53.5 bits (126), Expect = le-06 Identities = 42/149 (28%), Positives = 70/149 (46%), Gaps = 9/149 (6%) Query: 34 IASNTVGNGKTSWAVRLLQRYLAETALDGRIVEKGMFVVSAQLLTEFGDYNYFQTMQEFL 93 + S G GK+ A+ +L+ L T L ++ V + F + + F + + F+ Sbjct: 155 VVSGPAGTGKSHLAMSILKDCLQHTDLT--VIFASWSEVLHLIKDSFDNKDSFYSTEYFM 212 WO 00/32825 PCT/IB99/02040 408 Query: 94 ERFERLKTCELLVIDEIGGGSLTKASYPYLYDLVNYRVDNNLSTIYTTNYTDDEIIDLLG 153 E F + +LLVID+IG +T+ S L ++++ R TI TTN DEI Sbjct: 213 EVF---RNTDLLVIDDIGSEKITEWSMSLLTEVLDART----KTIITTNLKSDEIRKKYH 265 Query: 154 QRLYSRIYDTSVVLDFQASNVRGLEVSEI 182 R YSR++ F N++ VS++ Sbjct: 266 NRTYSRLFRGIGKKAFNFENIKDKRVSQL 294 Query= sid|114859IlanjdplORF038 Phage dpl ORF11350-187113 (173 letters) >spIP441231YB90_HAEIN HYPOTHETICAL PROTEIN HI1190 >gil1074675|pirl |F64021 hypothetical protein HI1190 - Haemophilus influenzae (strain Rd KW20) >gil1574117 (U32798) 6-pyruvoyl tetrahydrobiopterin synthase, putative [Haemophilus influenzae Rd Length = 141 Score = 100 bits (247), Expect = 6e-21 Identities = 59/143 (41%), Positives = 83/143 (57%), Gaps = 10/143 (6%) Query: 2 RVSKTLTFDAAHQLVGHFGKCANLHGHTYKVEISLAGGTYDHGSSQGMVVDFYHVKKIA- 60 ++SK +FD AH L GH GKC NLHGHTYK+++ ++G Y G+ + MV+DF +K I Sbjct: 3 KISKEFSFDMAHLLDGHDGKCQNLHGHTYKLQVEISGDLYKSGAKKAMVIDFSDLKSIVK 62 Query: 61 GTFIDRLDHAVLL-QGNEP ---- IALANAVDTKRVLFGFRTTAENMSRFLTWTLTELMWK 115 +D +DHA + Q NE L +++K FRTTAE ++RF+ L + Sbjct: 63 KVILDPMDHAFIYDQTNERESQIATLLQKLNSKTFGVPFRTTAEEIARFIFNRLKH--DE 120 Query: 116 HARIDSIKLWETPTGCAECTYYE 138 I SI+LWETPT + C Y E Sbjct: 121 QLSISSIRLWETPT--SFCEYQE 141 Query= sidll4860|lanidplORF039 Phage dpi ORF13306-380313 (165 letters) >emb|CAA682441 (X99978) ORF7; hydophobic protein (Lactobacillus plantarum] Length = 168 Score = 64.4 bits (154), Expect = 5e-10 Identities = 49/156 (31%), Positives = 84/156 (53%), Gaps = 9/156 (5%) Query: 8 WLVRTALIAALYVTLTVAFSAISY--GPIQFRVSEALILLPLWNHRWTPGIVLGTIIANF 65 W++ AL+AA+YV L + +A S G IQFRVSE L L ++N ++ GIV G I+ + Sbjct: 9 WIIN-ALVAAMYVVLCLGPAAFSLASGAIQFRVSEGLNHLAVFNRKYIWGIVAGVILFDA 67 Query: 66 FSP-LGLIDVLFGSLATFLGXXXXXXXXXXXSPLYSLICPVLA--- -NAYLIALELRIVY 120 F P L++VLFG + L ++ + +A + ++IAL + ++ Sbjct: 68 FGPGASLLNVLFGGGQSLLALLVLTWLAPKLKTVWQRMLLNIALFTVSMFMIALMITMMS 127 Query: 121 S-LPFWESVIYVGISEAIIVLISYFLISTLAKNNHF 155 S + FW + + +SE II+ I+ ++ +L + HF Sbjct: 128 SGVAFWPTYLTTALSELIIMSITAPIMYSLDRVLHF 163 Query= sidI14862|lanldplORF041 Phage dpi ORF18208-869913 (163 letters) >gil2522313 (AF012906) dUTPase homolog [Bacillus subtilis] >gi12634394|emb|CAB138931 (Z99114) similar to deoxyuridine 5'-triphosphate nucleotidohydrolase [Bacillus subtilis] >gi|3025643 (AF020713) putative dUTPase (Bacteriophage SPBc2] Length = 142 Score = 108 bits (267), Expect = 2e-23 Identities = 65/160 (40%), Positives = 83/160 (51%), Gaps = 25/160 (15%) Query: 5 VDVKMIDPKLDRLKYT--GDWVDVRISSITKIDADSADVSRCRKVLQKAQVYSVAAGECI 62 + +K +D R+ GDW+D+R + I D + Sbjct: 3 IKIKYLDETQTRINKMEQGDWIDLRAAEDVAIKKDEFKL----------------------- 41 Query: 63 KIAHGFALELPKGYEAILHPRSSLFKKTGLIFVSS-GVIDEGYKGDTDEWFSVWYATRDA 121 + G A+ELP+GYEA + PRSS +K G+I +S GVIDE YKGD D WF YA RD Sbjct: 42 -VPLGVAMELPEGYEAHVVPRSSTYKNFGVIQTNSMGVIDESYKGDNDFWFFPAYALRDT 100 WO 00/32825 PCT/IB99/02040 409 Query: 122 DIFYDQRIAQFRIQEKQPAIKFNFVESLGNAARGGHGSTG 161 I RI QFRI +K PA+ V+ LGN RGGHGSTG Sbjct: 101 KIKKGDRICQFRIMKKMPAVDLIEVDRLGNGDRGGHGSTG 140 Query= sidI114867|lanIdplORF046 Phage dpi ORF142774-4320213 (142 letters) >embiCABO79841 (Z93946) hypothetical protein [bacteriophage Dp-1] Length = 142 Score = 287 bits (728) , Expect = 2e-77 Identities = 142/142 (100%) , Positives = 142/142 (100%) Query: 1 MPMWLNDTAVLTTIITACSGVLTVLLNKLFEWKSNKAKSVLEDISTTLSTLKQQVDGIDQ 60 MPMWLNDTAVLTTIITACSGVLTVLLNKLFEWKSNKAKSVLEDISTTLSTLKQQVDGIDQ Sbjct: 1 MPMWLNDTAVLTTIITACSGVLTVLLNKLFEWKSNKAKSVLEDISTTLSTLKQQVDGIDQ 60 Query: 61 TTVAINHQNDVIQDGTRKIQRYRLYHDLKREVITGYTTLDHFRELSILFESYKNLGGNGE 120 TTVAINHQNDVIQDGTRKIQRYRLYHDLKREVITGYTTLDHFRELSILFESYKNLGGNGE Sbjct: 61 TTVAINHQNDVIQDGTRKIQRYRLYHDLKREVITGYTTLDHFRELSILFESYKNLGGNGE 120 Query: 121 VEALYEKYKKLPIREEDLDETI 142 VEALYEKYKKLPIREEDLDETI Sbjct: 121 VEALYEKYKKLPIREEDLDETI 142 Query= sidI114901lanIdplORFO8O Phage dpi ORF142490-4275911 (89 letters) >embICABO7983| (Z93946) hypothetical protein [bacteriophage Dp-1] Length = 124 Score = 147 bits (367) , Expect = le-35 Identities = 75/75 (100%), Positives = 75/75 (100%) Query: 1 MLNLTKSRQIVAEFTIGQGAEKKLVKTTIVNIDANAVSTVSETLHDPDLYAANRRELRAD 60 MLNLTKSRQIVAEFTIGQGAEKKLVKTTIVNIDANAVSTVSETLHDPDLYAANRRELRAD Sbjct: 1 MLNLTKSRQIVAEFTIGQGAEKKLVKTTIVNIDANAVSTVSETLHDPDLYAANRRELRAD 60 Query: 61 EQKLRETRYAIEDEI 75 EQKLRETRYAIEDEI Sbjct: 61 EQKLRETRYAIEDEI 75 Query= sidIl14912llanIdplORF091 Phage dpl ORF143189-4341311 (74 letters) >embICABO7985| (Z93946) holin [bacteriophage Dp-1] Length = 74 Score = 63.2 bits (151), Expect = 2e-10 Identities = 34/74 (45%), Positives = 34/74 (45%) Query: 1 MKLSNEQYD XXQFDXXXXXXXXXXXXXXXXXVLGVSSR 60 MKLSNEQYD YQFD VLGVSSR Sbjct: 1 MKLSNEQYDVAKNVVTVVVPAAIALITGLGALYQFDTTAITGTIALLATFAGTVLGVSSR 60 Query: 61 NYQKEQEAQNNEVE 74 NYQKEQEAQNNEVE Sbjct: 61 NYQKEQEAQNNEVE 74 WO 00/32825 PCT/IB99/02040 410 Condensed listing of homology information from above Phage: dp1 Database: nr Program: Blastp Query= sid|114822|lanjdp1ORF001 Phage dpl ORF136698-4039012 (1230 letters) giJ2444124 (U88974) ORF45 (Streptococcus thermophilus temperate ... 467 e-130 giJ928828 (L44593) ORF1904; putative [Lactococcus lactis phage B... 427 e-11 gil2935 6 76 (AF032121) unknown [Streptococcus thermophilus bacter... 309 le-82 gil2935691 (AF032122) unknown [Streptococcus thermophilus bacter ... 306 7e-82 giJ3540289 (AF057033) putative anti-receptor [Streptococcus ther ... 279 6e-74 gij45301541gb|AAD21894.1| (AF085222) putative tail-host specific... 220 3e-56 gil930045|emb|CAA33387| (X15332) alpha-1 (III) collagen [Homo sa ... 58 4e-07 gi[1070603jpir||CGHU7L collagen alpha 1(III) chain precursor - h ... 58 4e-07 gil4502951|ref|NP_000081.1|PCOL3AIl collagen, type III, alpha 1 ... 58 4e-07 gil115290|spIP042581CA13_BOVIN COLLAGEN ALPHA 1(III) CHAIN >gil7 ... 58 4e-07 gil575322|embiCAA362791 (X52046) type III collagen [Mus musculus] 57 8e-07 giJ21191631pir||S59856 collagen alpha 1(III) chain precursor - m... 57 8e-07 gil543912|spIP139411CA13_RAT COLLAGEN ALPHA 1(III) CHAIN >gil543 ... 57 le-06 gil3171998|embICAA06510| (AJ005395) collagen alpha 1 (III) [Ratt ... 57 le-06 gil3947565|embICAA902501 (Z49967) similar to collagen; cDNA EST ... 54 7e-06 gil4234031pir|IA46053 bullous pemphigoid antigen, BPAG2, type XV... 53 9e-06 giJ115410|spIP12114|CCSi_CAEEL CUTICLE COLLAGEN SQT-1 >giJ844371 ... 53 9e-06 gil3873801|embiCAA90084| (Z49907) cuticle collagen SQT-1; cDNA E ... 53 9e-06 Query= sid|l14823|lanjdplORF002 Phage dpi ORF132386-3583511 (1149 letters) gi|3341922|dbjIBAA31888| (AB009866) orf 15 {bacteriophage phi PVL] 280 3e-74 giJ4126622|dbjIBAA36642.1| (AB016282) ORF36 [bacteriophage phi-105] 232 ie-59 gi11369948|embICAA591941 (X84706) host interacting protein [Bact ... 201 3e-50 giJ3139112 (AF063097) gpT [Bacteriophage P2] 188 2e-46 gil3337272 (U32222) G protein [Bacteriophage 186] 161 3e-38 gil4063799ldbjIBAA36253 (AB008550) orf25; similar to T gene of ... 159 8e-38 gi|3172274 (AF022214) minor tail subunit; putative tape-measure ... 123 6e-27 gil465127|sp|Q052331VG26_BPML5 MINOR TAIL PROTEIN GP26 >giJ41904 ... 108 2e-22 giJ3540284 (AF057033) putative minor tail protein [Streptococcus... 99 2e-19 giJ2444119 (U88974) ORF40 [Streptococcus thermophilus temperate ... 90 6e-17 gil26345551emb|CABi40531 (Z99115) yomI [Bacillus subtilis] >giJ3 ... 66 le gil2392838 (AF011378) unknown [Bacteriophage ski] 64 5e-09 gil2764873|embICAA66557| (X97918) gene 18.1 [Bacteriophage SPP1] 62 3e-08 giJ1353559 (U38906) ORF42 [Bacteriophage rt] 61 6e-08 gi|630841|pir||S39079 puff C-8 protein - fungus gnat (Rhynchosci ... 55 2e-06 gil17308651spIP517311YO27_BPHP1 HYPOTHETICAL 72.8 KD PROTEIN IN ... 53 8e-06 giJ224288|prf|11101273J ORF 7 (Bacteriophage HP1} 53 le-OS Query= sidj114824|lanIdp1ORF003 Phage dpi ORF153538-5587713 (779 letters) giI118825|splP00582IDPO1_ECOLI DNA POLYMERASE I (POL I) >giJ6705 ... 193 3e-48 gil29821021pdb|1KFSIA Chain A, All-Oxygen Dna Complexed To The 3... 193 3e-48 gil2298891pdbI1DPI| DNA Polymerase I (Klenow Fragment) (E.C.2 .... 193 3e-48 gil1169402jsp|P43741|DPO1_HAEIN DNA POLYMERASE I (POL I) >gil107 ... 191 le-47 gil2688462 (AE001156) DNA polymerase I (polA) [Borrelia burgdorf... 190 3e-47 gij809180|pdbIlKLNIA Escherichia coli 190 3e-47 gil1913934|embICAA72997| (Y12328) DNA-directed DNA polymerase I ... 189 8e-47 gij4090935 (AF028719) DNA polymerase type I [Rhodothermus sp. 'I .. 175 e-42 gil4731571lgb|AAD28505.11AF121780_1 (AF121780) DNA polymerase I ... 174 2e-42 gi|1633576 (U57757) similar to proofreading 3'-5' exonuclease an... 173 4e-42 gil3322368 (AE001195) DNA polymerase I (polA) [Treponema pallidum] 172 9e-42 gil1006595|dbjiBAA10748| (D64005) DNA polymerase I (Synechocysti... 171 2e-41 gil585062|spIQ07700IDPO1_MYCTU DNA POLYMERASE I (POL I) >gil4161 ... 163 5e-39 gil43769081gbjAAD187511 (AE001645) DNA Polymerase I Chlamydia p... 157 2e-37 gilI169403|spIP46835IDPO1_MYCLE DNA POLYMERASE I (POL I) >gi^1107 ... 152 7e-36 gil2145839|pirI lS72949 DNA polymerase I - Mycobacterium leprae >... 152 7e-36 giJ1405438|embICAA671841 (X98575) DNA-dependent DNA polymerase [... 1 2 9e-36 gil2506365|splP80194|DPO1_THECA DNA POLYMERASE I, THERMOSTABLE (... 147 2e-34 giJ3328929 (AE001322) DNA Polymerase I [Chiamydia trachomatis) 147 3e-34 WO 00/32825 PCT/IB99/02040 411 gi|3913510|splO52225IDPO1_THEFI DNA POLYMERASE I, THERMOSTABLE (... 146 7e-34 gi1l205984 (U33536) DNA polymerase I [Bacillus stearothermophilus} 146 7e-34 gil1188271sp|P13252|DP0l_STRPN DNA POLYMERASE I (POL I) >gil9802 ... 145 9e-34 gil19422021pdbIlJXEI Stoffel Fragment Of Taq Dna Polymerase I 145 le-33 gil1943520|pdb|lKTQI Dna Polymerase 145 le-33 gil1084022|pir||JX0359 DNA-directed DNA polymerase (EC 2.7.7.7) ... 145 le-33 gil507891|dbjIBAA067751 (D32013) DNA Polymerase [Thermus aquaticus] 145 le-33 gil1188281spIP19821IDPO1_THEAQ DNA POLYMERASE I, THERMOSTABLE (T ... 145 le-33 giI1706502|sp|P52028IDPO1_THETH DNA POLYMERASE I, THERMOSTABLE ( ... 144 2e-33 gil10972111prfI|2113329A DNA polymerase [Thermus aquaticus therm... 144 2e-33 gil2098289|pdbIlTAUJA Chain A, Structure Of Dna Polymerase 143 3e-33 Query= sidll4825|lanIdplORF004 Phage dpl ORF140401-4244013 (679 letters) gil1934761lemb|CAB079811 (Z93946) hypothetical protein (bacterio ... 1011 0.0 gil3540290 (AF057033) putative minor structural protein [Strepto ... 346 2e-94 giJ2444125 (U88974) ORF46 [Streptococcus thermophilus temperate ... 339 3e-92 gil1934762|embICAB07982| (Z93946) hypothetical protein (bacterio ... 300 2e-80 gi|45301551gblAAD21895.1 (AF085222) unknown [Streptococcus ther ... 276 4e-73 giJ2935677 (AF032121) unknown [Streptococcus thermophilus bacter... 250 3e-65 gi12935692 (AF032122) unknown [Streptococcus thermophilus bacter ... 250 3e-65 gil1136289 (U42597) histidine kinase A (Dictyostelium discoideum] 50 7e-05 Query= sidll14827jlanldplORF006 Phage dpi ORF145296-4698712 (563 letters) giJ43771651gbIAAD18987 (AE001666) SWI/SNF family helicase_2 [Ch ... 171 le-41 gi|1769947lemb|CAA67095| (X98455) SNF [Bacillus cereus] 160 3e-38 gil3329163 (AE001341) SWF/SNF family helicase (Chlamydia trachom... 159 6e-38 gil4377149|gb|AAD18973| (AE001664) SWI/SNF family helicase_1 [Ch ... 157 2e-37 gil3328995 (AE001326) SWI/SNF family helicase [Chlamydia trachom ... 153 2e-36 gil2493354|splP75093|Y018_MYCPN HYPOTHETICAL HELICASE MG018/MG01 ... 146 4e-34 gi|1653748|dbj|BAA186591 (D90916) helicase of the snf2/rad54 fam... 143 3e-33 gil1763712lemb|CAB059391 (Z83337) member of the SNF2 helicase fa ... 143 4e-33 gil2636153lembICAB15645.11 (Z99122) similar to SNF2 helicase [Ba... 143 4e-33 gij2909552lembiCAA172841 (AL021924) helZ [Mycobacterium tubercul ... 140 2e-32 gi|3844627 (U39681) ATP-dependent RNA helicase, putative [Mycopl.... 136 3e-31 gi|13514631sp|P472641Y018_MYCGE HYPOTHETICAL HELICASE MG018 136 4e-31 giJ2660669 (AC002342) human Mi-2 autoantigen-like protein [Arabi... 131 2e-29 gil1361537|pirI 164201 helicase (mot1) homolog - Mycoplasma geni ... 129 4e-29 gi|3482977|emblCAA20533.1| (AL031369) putative protein [Arabidop. ... 128 9e-29 gi|3298562 (U91543) zinc-finger helicase [Homo sapiens 120 2e-26 gil3875971lemb|CAB02491| (Z80344) similar to helicase; cDNA EST ... 120 2e-26 gil4557451refINP_001263.1|PCD3| chromodomain helicase DNA bind... 120 2e-26 gil2645435 (AF007780) CHD3 [Drosophila melanogaster] 118 le-25 gi|3875165lemb|CAA91798| (Z67881) Similarity to Mouse Chromodoma. .. 118 le-25 Query= sidll4828IlanjdplORF007 Phage dpl ORF122230-2362113 (463 letters) gi12444105 (U88974) ORF26 [Streptococcus thermophilus temperate ... 89 7e-17 gij3318666 (U19754) BBA31 homolog [Borrelia burgdorferi] 59 7e-08 gil2690260 (AE000790) conserved hypothetical protein [Borrelia b... 56 5e-07 Query= sidll4829llanIdplORF008 Phage dpi ORF149624-5096111 (445 letters) gil4406210|gbIAAD19901| (AF100420) DnaB replication fork helicas ... 68 2e-10 giJ3121983|spIO25916|DNAB_HELPY REPLICATIVE DNA HELICASE >gil231... 67 2e-10 gi|4416322|gb|AAD203141 (AF106032) replicative helicase; DnaB [B... 65 9e-10 gi|4155895 (AE001551) REPLICATIVE DNA HELICASE [Helicobacter pyl ... 60 4e-08 gi|3322317 (AE001191) replicative DNA helicase (dnaB) [Treponema. .. 58 le-07 gil1380311splP045301VG41_BPT4 PRIMASE-HELICASE (PROTEIN GP41) >g ... 53 3e-06 giJ2983861 (AE000742) replicative DNA helicase [Aquifex aeolicus] 51 le-05 Query= sidlll4831llanldplORF010 Phage dpl ORF18699-985912 (386 letters) gil2760912 (AF037258) RecA protein [Chlorobium tepidum] 133 2e-30 gi|32198511spjP94666|RECACLOPE RECA PROTEIN >gil1698591 (U61497 ... 129 3e-29 gi113505661spIP482951RECASTRVL RECA PROTEIN >gil508860 (U04837) ... 128 7e-29 gi17441631prf||2014250A recA-like protein [Streptomyces violaceus] 126 3e-28 gi|730487|spIP41054|RECASTRAM RECA PROTEIN >gil511133|embICAA82 ... 125 4e-28 gil2687334lemblCAA158751 (AL020958) RecA protein [Streptomyces c ... 125 6e-28 giJ135OS651spIP482941RECA-STRLI RECA PROTEIN >gi14814821pir11S38 ... 125 6e-28 WO 00/32825 PCT/IB99/02040 412 gil464599|spIP33542IRECAAQUPY RECA PROTEIN >gil10861671pir|lA55... 123 2e-27 gil417636|sp|P32725|RECA_RHOSH RECA PROTEIN >gil541307|pir||S415 ... 123 2e-27 gil2984348 (AE000775) recombination protein RecA [Aquifex aeolicus] 123 2e-27 gi|3219854|splP95846|RECASTRRM RECA PROTEIN >giI17298001embICAA ... 122 4e-27 gil2500086|spIQ59560|RECAMYCSM RECA PROTEIN >gi|1430892|emb|CAA ... 122 4e-27 gi|1350567|spIP48296|RECATHEAQ RECA PROTEIN >gil10729631pir||A5... 122 6e-27 gi|625663|pir||JX0292 recA protein - Thermus aquaticus (strain HB8) 121 le-26 gil1172880|spIP42440|RECACAMJE RECA PROTEIN >gil21199911pir||I4... 120 2e-26 gil4154654 (AE001453) RECA PROTEIN. [Helicobacter pylori J99] 120 2e-26 gil1072968|pir||C55020 recA protein - Thermus sp >gil458472|dbj| ... 120 2e-26 gil3219852|spIP95469|RECA PARDE RECA PROTEIN >giJ1825468 (U59631 ... 119 3e-26 gil25072841sp|P42445|RECAHELPY RECA PROTEIN >gil2313235|gbIAADO ... 119 4e-26 gil11728901spIQ02350|RECASTAAU RECA PROTEIN >gil463285 (L25893)... 118 5e-26 gil44162091gblAAD202611 (AF094756) RecA protein [Bifidobacterium ... 118 Se-26 gil2S000841spIQ59180RECABORBU RECA PROTEIN >giI1276443 (U23457. ... 118 2e-26 Query= sid1ll483211anIdplORF0ll Phage dpi ORF128017-2909613 (359 letters) gi12444110 (U88974) ORF31 (Streptococcus thermophilus temperate ... 187 le-46 gi13320438 (AF057033) gp348 [Streptococcus thernophilus bacterio. ... 179 2e-44 gil4795141pirlIS134244 hypothetical protein p38 - actinophage VWB. ... 62 Be-OP Query= sidlll4834IlanidplORF013 Phage dpi ORF110215-1124013 (341 letters) giIS80855lembICAA299S81 (X06803) dnazx-like ORF put. DNA polymer ... 182 2e-45 9 ill18807Isp1P09122IDP3XBACSU DNA POLYMERASE III SUBUNITS GAMMA. ... 182 2e-45 gi1982921pir1 S13786 DNA-directed DNA polymerase (EC 2.7.7.7) 11I... 182 2e-45 gi11527142 (U66040) DNA polymerase III gamma subunit [Salmonella ... 172 4e-42 9 iI2494197Isp1P748761DP3X_SALTY DNA POLYMERASE III SUBUNITS GANM. ... 172 4e-42 gill88O81spIPO67lOIDP3X_ ECOLI DNA POLYMERASE III SUBUNITS GAM4MA. ... 170 le-41 giJ415207 (AE001497) DNA POLYMERASE III SUBUNITS GAMMA AND TAU .. . 169 2e-41 gij23l384l1gblAAl07767.11 (AE000584) DNA polymerase III gamma an .. . 168 4e-41 gi12583049 (AF025391) DNA polymerase III holoenzyme tau subunit . .. 166 3e-40 giJ2984127 (AE000759) DNA polymerase III gamma subunit [Aquifex . .. 166 3e-40 giJ386l3901embICAA152891 (AJ235273) DNA POLYNERASE III SUBUNITS ... 165 5e-40 giJ11693971spjP43746IDP3X_-HAEIN DNA POLYMERASE III SUBUNITS GANM. ... 156 2e-37 giJ1293572 (U49738) DNA polymerase III tau homolog DnaX [Cauloba ... 151 8e-36 gi13328753 (AE001306) DNA Po1 III Gamma and Tau (Chlamydia trach ... 148 4e-35 gil43762941gblAAD181931 (AE001589) DNA Polymerase III Gamma and . .. 148 5e-35 gilB81255lembjCAA28l751 (X04487) alternate dnaZX protein (AA 1-6 ... 146 3e-34 giJ2688379 (AE00li) DNA polymerase III, subunits garmma and tau ... 140 2e-32 gi3323329 (AE001268) DNA polymerase III, subunits gamma and tau ... 137 le-31 Query= sid|114832|lanjdplORF014 Phage dpl ORF150961-5197413 (337 letters) gill3467961spIP474921PRIM_-MYCGE DNA PRIMASE >giI13614961pirlI1F64. ... 57 2e-07 gil740008(prfI82004290A primase (Haemophilus influenzae] 51 le-46 gilll726l91spIQo83461PRIM_-HAEIN DNA PRIMASE >gill0740331pirj IA64. ... 51 le-OS giJl7O97691spiQO45oSIPRIM_-LACLA DNA PRIMASE >gijl075726jpirI IJC2. ... 51 le-OS gil639846dbjIBAA0356 (D14690) DNA primase [Lactococcus lactis] 51 le-44 Query= sid|ll4837lanidplORF016 Phage dpi ORF143413-4430313 (296 letters) gill934766embICAB79861 (Z93946) N-acetylmuramoyl-L-alanine ami .. 661 0.0 giJ113676splP0663 XALYS_STRPN AUTOLYSIN (N-ACETYLMURAMOYL-L-ALA... 221 4e-57 gij282326pir|1A42935 N-acetylmuramoyl-L-alanine amidase (EC 3.5 ... 219 3e-56 giJ4166l81spIP327621ALYS_BPHB3 LYTIC AMIDASE (N-ACETYLMURAI4OYL-L .. . 212 2e-54 gil2852731pir FA42936 N-acetylmuramoyl-L-alanine amidase (E 3.5... 212 2e-54 gijl277871spP107ILYCA_SBPCP1 LYSOZYME (ENDOLYSIN) (MURANIDASE) ... 162 4e-39 gil677611pirMUBPCP N-acetylmuramoyl-L-alanine amidase (EC 3.5 .... 162 4e-39 gil127789(spIP19386ILYCA BPCP9 LYSOZYME (ENDOLYSIN) (MURANIDASE) ... 160 le-38 gil928832 (144593) 0RF259; putative [Lactococcus lactis phage BK... 119 2e-26 gil251170embCAA77831 (Y10818) sigA binding protein (Streptoc ... 111 9e-24 giJ4097980 (U72655) surface protein C (Streptococcus pneumoniae] 107 le-22 gi12351768 (U89711) PspA [Streptococcus pneumoniae 105 4e-22 gi2425109 (AF019904) choline binding protein A [Streptococcus-p... 104 6e-22 gij28233S1pilI A41971 surface protein pspA precursor - Streptoco. ... 104 le-21 gil276331embiCAA0158 (AJ02054) SpsA protein [Streptococcus ... 103 2e-21 gil2l272951pirlISS7962 cspC protein - Clostridium acetobutylicum ... 85 6e-16 gil2576333embCAA05159 (AJ02)) SpsA protein (Streptococcus ... 84 le-5 gi4l0622gbAA02874.1 (AF097909) excreted protein FibB [Pepty .m. 83 3e gill36l4 1pirlI S57714 cspB protein - Clostridium acetobutylicum. . 1. 82 4e-45 giJ19148721embICAB047581 (Z82001) PCPA [Streptococcus pneumoniae) 81 9e-15 WO 00/32825 PCT/IB99/02040 413 gil3168594IdbjIBAA28613I (AB012763) SpaA (Erysipelothrix rhusiop. 81 le-14 gil2292750|embiCAA64942| (X95646) homology to orf259 of lactococ. 80 3e-14 gil2935696 (AF032122) putative lysin (Streptococcus thermophilus. 80 3e-14 gil4586910|dbjlBAA76540.1| (AB017447) protective antigen SpaA.1 80 3e-14 gil3540294 (AF057033) lysin [Streptococcus thermophilus bacterio... 79 Be-14 Query= sid114841[landplORF020 Phage dpi ORF11864-265811 (264 letters) gil2633745[embICAB13247 (Z99111) similar to coenzyme PQQ synthe. 217 5e-6 gil2808502|embiCAA12532I (AJ225561) ExsD protein [Sinorhizobium ... 163 le-9 gij3861151lembICAA15051| (AJ235272) unknown [Rickettsia prowazekii] 82 6e-15 gil1652793|dbjjBAA17712| (D90908) hypothetical protein (Synechoc. 76 3e-13 gil17238151spIP55139|YGCF_ECOLI HYPOTHETICAL 25.0 KD PROTEIN IN ... 70 2e-11 gi12984272 (AE000769) hypothetical protein (Aquifex aeolicus] 66 4e-10 gi[4155435 (AE001516) putative [Helicobacter pylori J99] 57 le-07 gil2127833|pirlC64505 coenzyme PQQ synthesis protein III homolo... 55 e-07 gil2622338 (AE000890) coenzyme PQQ synthesis protein III (Methan. 54 9e-07 gi|3257042IdbjIBAA29725l (AP000003) 254aa long hypothetical prot... 53 2e-06 gil23140681gb|AAD07976.11 (AE000602) conserved hypothetical prot... 52 6e-06 gil1723816|spIP450971YGCFHAEIN HYPOTHETICAL PROTEIN H11189 >gil... 50 2e-05 Query= sidll4842|1anldplORF021 Phage dpi ORF12504-329512 (263 letters) gil1274811spIP19465|GCH1_BACSU GTP CYCLOHYDROLASE I (GTP-CH-I) >... 208 4e-53 gil3242315|embICAA04237| (AJ000685) GTP cyclohydrolase (Streptoc... 191 4e-48 gil2494695|spIQ54769|GCH1_SYNP7 GTP CYCLOHYDROLASE I (GTP-CH-I) ... 189 2e-47 gil2550611bbs1112832 (S44049) GTP cyclohydrolase I (clone hGCH-1... 187 7e-47 gil45039491ref|NP_000152.1|PGCH1 GTP cyclohydrolase 1 (dopa-res... 187 7e-47 gil2113967|embICAB08935| (Z95557) folE [Mycobacterium tuberculosis] 187 7e-47 giI1730240|spIP50141IGCH1_CHICK GTP CYCLOHYDROLASE I (GTP-CH-I) ... 185 3e-46 gil2494696IspIQ55759|GCH1_SYNY3 GTP CYCLOHYDROLASE I (GTP-CH-I) ... 184 5e-46 giI121061|spIP22288|GCH1_RAT GTP CYCLOHYDROLASE I PRECURSOR (GTP.. 184 6e-46 giJ3183014|spIO13774|GCH1_SCHPO GTP CYCLOHYDROLASE I (GTP-CH-I) ... 184 6e-46 gil3097224|embiCAA187951 (AL023093) GTP cyclohydrolase I [Mycoba. 182 2e-45 gil2494697|sp|Q19980|GCH1_CAEEL PROBABLE GTP CYCLOHYDROLASE I (G... 182 2e-45 gi14621671SpIQ05915|GCH1_MOUSE GTP CYCLOHYDROLASE I PRECURSOR (G... 180 7e-45 gil16696641emb|CAA898081 (Z49706) GTP cyclohydrolase I [Dictyost ... 180 le-44 gil2981082 (AF052048) GTP-cyclohydrolase (Ostertagia ostertagi] 178 3e-44 gil319541embjCAA789081 (Z16418) GTP cyclohydrolase I (Homo sapi... 177 8e-44 gil5513441bbs|150280 (S71373) GTP cyclohydrolase I [mice, Peptid ... 174 5e-43 gil17302471spIP51601|GCH1_YEAST GTP CYCLOHYDROLASE I (GTP-CH-I) ... 174 7e-43 gil1246912|embICAA873971 (Z47201) GTP cyclohydrolase 1 [Saccharo... 172 2e-42 gil1730246|spIPS1595|GCH1_STRPN GTP CYCLOHYDROLASE I (GTP-CH-I) ... 168 3e-41 gil2982951 (AE000680) GTP cyclohydrolase I [Aquifex aeolicus] 164 6e-40 Query= sidj114843llanjdp1ORF022 Phage dpi ORF130896-3167512 (259 letters) gil2347102 (U77367) internalin (Listeria monocytogenes] 55 Se-07 gi|3123226|spIP25146|INLALISMO INTERNALIN A PRECURSOR >giJ48705 ... 52 4e-06 gil149674 (M67471) internalin [Listeria monocytogenes] 52 4e-06 Query= sid|l14850|lanIdp1ORF029 Phage dpi ORF1662-134812 (228 letters) giJ2650185 (AE001074) succinoglycan biosynthesis regulator (exsB ... 119 2e-26 gil3861231lembCAA15131 (AJ235272) unknown [Rickettsia prowazekii] 117 8e-26 gil2622210 (AE000881) conserved protein [Methanobacterium thermo... 108 4e-23 gil2983380 (AE000709) trans-regulatory protein ExsB [Aquifex aeo... 88 6e-17 gil1001327|dbjIBAA10814| (D64006) ExsB [Synechocystis sp.] 88 6e-17 gij2l28055|pir|IB64468 hypothetical protein homolog MJ1347 - Met... 83 le-iS giJ4155143 (AE001491) putative [Helicobacter pylori J99] 82 4e-15 gil23137601gbIAAD07701.1| (AE000578) conserved hypothetical prot... 80 2e-14 gil21208141pir||S60183 protein ExsB - Rhizobium meliloti >gil114... 76 3e-13 gil2633743|embICAB13245| (Z99111) similar to hypothetical protei... 75 5e-13 gil1175543|spIP44124|YBAXHAEIN HYPOTHETICAL PROTEIN HI1191 >gil ... 74 le-12 gil2495537|spIP777561YBAXECOLI HYPOTHETICAL 25.5 KD PROTEIN-IN ... 71 5e-12 gi|3256471|dbjjBAA29154.1| (AP000001) 269aa long hypothetical pr... 67 le-lO gil2921156 (AF022216) aluminum resistance protein [Arthrobacter ... 54 le-06 Query= sid|114855|lanjdp1ORF034 Phage dpi ORF1131-65212 (173 letters) gil2633746lembICAB132481 (Z99111) similar to hypothetical protei. ... 220 4e-57 WO 00/32825 PCT/IB99/02040 414 giJ4155926 (AE001554) putative Helicobacter pylori J99] 162 le-39 gil23145881gblAAD08456.1| (AE000642) conserved hypothetical prot... 161 3e-39 gil2983458 (AE000714) hypothetical protein [Aquifex aeolicus] 103 9e-22 gil1006604ldbjiBAA10757| (D64005) hypothetical protein (Synechoc... 87 6e-17 gil2967529 (U11045) unknown (Buchnera aphidicola] 79 2e-14 gil24956541spIQ46920|YQCD_ECOLI HYPOTHETICAL 32.6 KD PROTEIN IN 69 2e-11 gi|1l75604|spIP44153|YQCD_HAEIN HYPOTHETICAL PROTEIN HI1291 >gil... 63 le-09 gi|3860642|emb|CAA145431 (AJ235270) unknown [Rickettsia prowazekii) 56 le-07 Query= sid|114857|lanIdp1ORF036 Phage dpi ORF148808-4936211 (184 letters) gil1353529 (U38906) ORF12 (Bacteriophage r1t] 53 le-06 Query= sid|114859|lanjdplORF038 Phage dpl ORF11350-187113 (173 letters) gi[l1755421spIP44123|YB90_HAEIN HYPOTHETICAL PROTEIN H11190 >gil... 100 6e-21 gil2982977 (AE000681) hypothetical protein [Aquifex aeolicus] 67 7e-11 gij3860744|emb|CAA146451 (AJ235270) unknown (Rickettsia prowazekii] 65 3e-10 gi12650193 (AE001074) conserved hypothetical protein (Archaeoglo... 58 4e-08 gil3258383|dbj|BAA31066.1 (AP000007) 157aa long hypothetical pr ... 55 2e-07 gill0O1713|dbjiBAA10550| (D64004) hypothetical protein [Synechoc ... 50 8e-06 gil4155434 (AE001516) putative (Helicobacter pylori J99] 50 le-05 Query= sid|114860jlanIdp1ORF039 Phage dpl ORF13306-380313 (165 letters) gil1922884lemb|CAA68244| (X99978) ORF7; hydophobic protein [Lact ... 64 5e-10 Query= sid|114862|lanjdp1ORF041 Phage dpi ORF18208-869913 (163 letters) gil2522313 (AF012906) dUTPase homolog (Bacillus subtilis] >gil26 ... 108 2e-23 gil2634150|embICAB13650| (Z99113) similar to deoxyuridine 5'-tri... 108 3e-23 gi|39135461sp|0541341DUTSTRCO DEOXYURIDINE 5'-TRIPHOSPHATE NUCL... 56 2e-07 gil3913542|sp|O48500lDUT_BPT5 DEOXYURIDINE 5'-TRIPHOSPHATE NUCLE ... 52 3e-06 gi|3913548|spIO689921DUTCHLTE DEOXYURIDINE 5'-TRIPHOSPHATE NUCL... 50 le-05 Query= sidI114867|lanidplORF046 Phage dpl ORF142774-4320213 (142 letters) gil1934764|embICAB07984| (Z93946) hypothetical protein bacteriao ... 287 2e-77 Query= sidl114901|lanjdplORF080 Phage dpl ORF142490-4275911 (89 letters) gil1934763|emb|CAB079831 (Z93946) hypothetical protein (bacterio ... 147 le-35 Query= sidI114912lanidplORF091 Phage dpi ORF143189-4341311 (74 letters) gil1934765|emb(CAB079851 (Z93946) holin [bacteriophage Dp-1] 63 2e-10 WO 00/32825 PCT/IB99/02040 415 Table 32 Sequence of Dpi published by Sheehan and al.. 4731 nucleotides. 1 tttaaatttt ttgacaaagt taattcaaat tgtaccgctg aagcaatttt ccatgtattc actcaaagtt 71 gttcagtgtg gctcaatcat attaaaatcg aacttggtaa tatctctact ccttttagtg aagcagagga 141 agaccttaaa tatcgaattg actcaaaagc cgatcaaaag ctaactaacc aacagttgac ggcactcacg 211 gaaaaggctc aactacatga cgcagaactg aaagctaagg ctacaatgga gcagttaagt aacttagaaa 281 aggcttatga aggtagaatg aaagctaatg aagaagctat caacaaatcg gaacccgacc taatcttagc 351 ggcaagtcga attgaagcta ctatccaaga acttggcggg ctacgggaac tgaagaagtt cgtcgacagt 421 tgcatgagct cttctaatca aggtctaatt atcggtaaga acgacggtag Ctctaccatt aaggtatcaa 491 gtgaccgaat ttctatgttc tccgcaggga atgaagttat gtaccttacg caagggttca ttcacatcga 561 taacgggatc tttacccaat ccattcaagt cggccgattt agaacggaac aatactcgtt taatccagac 631 atgaacgtga ttcggtatgt aggataagga gaataacatg acaaaattta tcaactcata cggccctctt 701 cacttgaacc tttacgtcga acaagttagt caggacgtaa cgaacaactc ctcgcgagtt agttggcgag 771 ctactgtcga ccgcgatgga gcttatcgaa cgtggactta tggaaatatt agtaaccttt ccgtatggtt 841 aaatggttca agtgttcata gcagtcaccc agactacgac acgtccggcg aagaggtaac gctcgcaagt 911 ggagaagtga ctgttcctca caatagtgac gggacaaaga caatgtccgt ttgggcttcg tttgacccta 981 ataacggcgt tcacggaaat atcactatct ctactaatta cactttagac agtattccaa ggtctacaca 1051 gatttctagt tttgagggaa atcgaaatct aggatcttta catacggtta tctttaaccg aaaagtgaac 1121 tcttttacgc atcaagtttg gtaccgagtt ttcggtagcg actggataga tttaggtaag aaccatacta 1191 ctagcgtatc ctttacgccg tcactggact tagcaaggta cttacctaaa tcaagttccg gaacaatgga 1261 catctgtatt cgaacctata acggaactac gcaaattggt agtgacgtct attcaaacgg atggaggttc 1331 aacatccccg attcagtacg tcctactttt tcgggcattt ctttagtaga cacgacttca gcggttcgac 1401 agattttaac agggaacaac ttcctccaaa tcatgtcgaa cattcaagtc aacttcaaca atgcttccgg 1471 cgcttacgga tccactatcc aagcatttca cgctgagctc gtaggtaaaa accaagctat caacgaaaac 1541 ggcggcaaat tgggtatgat gaactttaat ggctccgcta ccgtaagagc atgggttaca gacacgcgag 1611 gaaaacaatc gaacgtccaa gacgtatcta tcaatgttat agaatactat ggaccgtcta tcaatttctc 1681 cgttcaacgt actcgtcaaa atcctgcaat tatccaagct cttcgaaatg ctaaggtcgc acctataacg 1751 gtaggaggtc aacagaaaaa catcatgcaa attaccttct ccgtggcgcc gttgaacact actaatttca 1821 cagaagatag aggttcggcg tcagggacgt tcactactat ttccctactg actaactcgt ccgcgaactt 1891 agctggtaac tacgggccgg acaagtctta catagttaag gctaaaatcc aagacaggtt cacttcgact 1961 gaatttagtg ctacggtacc taccgaatca gtagttctta actatgacaa ggacggtcga cttggagttg 2031 gtaaggttgt agaacaaggg aaggcagggt caattgatgc agcaggtgat atatatgctg gaggtcgaca 2101 agttcaacag tttcagctca ctgataataa tggagcattg aacaggggtc aatataacga tgttggaata 2171 agcgtgaaac agagtttaca tggcgaagta acaaatacga ggacaaccct acgggaactc gaggtgaatg 2241 gggactattt caaaatttct ggttagatag ctggaaaatg gttcaatcct tcattacaat gtcaggaaga 2311 atgttcatca ggacagcgaa cgatggaaac agctggagac ctaacaagtg gaaagaggtt ctatttaagc 2381 aagacttcga acagaataat tggcagaaac ttgttcttca aagtgggtgg aaccatcact caacctatgg 2451 cgacgcattc tattcgaaaa ctcttgacgg catagtatat ttgagaggaa atgtgcataa aggacttatc 2521 gacaaagagg ctactattgc agtacttcCt gaaggattta gaccgaaagt ttcaatgtat cttcaggctc 2591 tcaataactc atatggaaat gccattctat gtatatacac tgacggaaga cttgtggtga aatcgaatgt 2661 agataattct tggttaaatt tagacaatgt ctcatttcgt atttaatttg agctgaaatc atgttataat 2731 attttttaga aaggaggtga gaactatgtt raaccttaca aaatcgcgcc aaattgtggc agagttcact 2801 attggacaag gagctgaaaa gaaacttgtc aaaacaacga ttgtgaacat tgatgcaaac gcagtatcaa 2871 ccgtctctga aactcttcat gacccagact tgtatgctgc gaaccgtcga gaacttcgag ctgacgagca 2941 aaaacttcgc gaaactcgtt acgcaatcga agatgaaatt aatagctgga gcgggggaaa aaagggggag 3011 cccggctcta acaggctgaa taaggaggcg tcaatctatg ccaatgtggc taaacgacac cgcagtcttg 3081 acgacgatta ttacagcgtg cagcggagtg cttactgtcc tactaaataa gttattcgaa tggaaatcga 3151 ataaagccaa gagcgtttta gaggatatct ctacaactct tagcactctt aaacagcagg tcgacgggat 3221 tgaccaaacg acagtagcaa tcaatcacca aaatgacgtc attcaagacg gaactagaaa aattcaacgt 3291 taccgtcttt atcacgactt aaaaagggaa gtgataacag gctatacaac tctcgaccat tttagagagc 3361 tctctatttt attcgaaagt tataagaacc ttggcggaaa tggtgaagtt gaagccttgt atgaaaaata 3431 caagaaatta ccaattaggg aggaagattt agatgaaact atctaacgaa caatatgacg tagcaaagaa 3501 cgtggtaacc gtagtcgttc cagcagcgat tgcactaatt acaggtcttg gagcgttgta tcaatttgac 3571 actactgcta tcacaggaac cattgcactt cttgcaactt ttgcaggtac tgttctagga gtttctagcc 3641 gaaactacca aaaggaacaa gaagctcaaa acaatgaggt ggaataatgg gagtcgatat tgaaaaaggc 3711 gttgcgtgga tgcaggcccg aaagggtcga gtatcttata gcatggactt tcgagacggt cctgatagct 3781 atgactgctc aagttctatg tactatgctc tccgctcagc cggagcttca agtgctggat gggcagtcaa 3851 tactgagtac atgcacgcat ggCttattga aaacggttat gaactaatta gtgaaaatgc tccgtgggat 3921 gctaaacgag gcgacatctt catctgggga cgcaaaggtg ctagcgcagg cgctggaggt catacaggga 3991 tgttcattga cagtgataac atcattcact gcaactacgc ctacgacgga atttccgtca acgaccacga 4061 tgagcgttgg tactatgcag gtcaacctta ctactacgtc tatcgcttga ctaacgcaaa tgctcaaccg 4131 gctgagaaga aacttggctg gcagaaagat gctactggtt tctggtacgc tcgagcaaac ggaacttatc 4201 caaaagatga gttcgagtat atcgaagaaa acaagtcttg gttctacttt gacgaccaag gctacatgct 4271 cgctgagaaa tggttgaaac atactgatgg aaattggtat tggttcgacc gtgacggata catggctacg 4341 tcatggaaac ggattggcga gtcatggtac tacttcaatc gcgatggttc aatggtaacc ggttggattT 4411 agtattacga taattggtat tattgtgatg ctaccaacgg cgacatgaaa tcgaatgcgt ttatccgtta 4481 taacgacggc tggtatctac tattaccgga cggacgtctg gcagataaac ctcaattcac cgtagagccg 4551 gacgggctca ttactgctaa agtttaaaat atagagagga ggaagctctt ttcttaatat tgtttctctt 4621 aatcccgcaa ggtttcgacc ctgcggggtt tatgtgtcgt gaattactct atttacttat tcgaagattt 4691 caattataat taaataatca acgagattca taattggagg aatg WO 00/32825 PCT/IB99/02040 416 Table 33 Streptococcus accession numbers gil57765531gblAF026471.21AF026471 [5776553] gil5231200IgblAF157824.11AF157824 [5231200] gil5410470|gb|AF139890.1IAF139890 [5410470] gil52311971gblAF157823.1 AFi57823 [5231197] gil5410468|gblAF139889.11AF1 3 9 88 9 [5410468] gi5231194gblAF157822.11AF157822 [5231194] gil5410466|gblAF139888.1|AF1 3 9 8 88 [5410466] gi523l191gbjAF157821.1IAF157821 [5231191] gil5410464gblAF139887.1|AF1 3 9 88 7 [5410464] gi52311881gbAF157820.1AF157820 [5231188] gil54104621gbjAF139886.1|AF 139 88 6 [5410462] gi5231185gbAF157819.11AF15781 9 [5231185] gil5410460jgblAF139885.1|AF13 9 8 8 5 [5410460] gi52311821gblAF157818.11AF1578 1 8 [5231182] gil5410458|gblAF139884.lAF 13 9 88 4 [5410458] guS 231 179igbAF157817.11AF157817 [5231179] gil5410456|gblAF139883.11AF1 3 9 8 83 [5410456] gi4336851gbAF106138.1AF106138 [4336851] gil3093394|emblAJO05697.11SPN5697 [3093394] gi4336848gblAFlO6137.11AF106137 [4336848] gil5759208|gblAF171873.1AF171873 [5759208] gi43368451gblAF106136. 1AF106136 [4336845] gil57583111gblAF162664.11AF1 6 26 64 [5758311] gi43368421gblAF106135.11AF106135 [4336842] gil5739313|gb|AF161701.1|AF1 6 1701 [5739313] gi43368391gblAF106134.1IAF10613 4 [4336839] gil573 9 3 1OIgblAF161700.11AF161700 [5739310] gi43368361gblAF106133.11AF106133 [4336836] gil5726354|gblAF159448.1|AF159448 [5726354] gi43368331gblAF106132.11AF106132 [4336833] gil5726290gblAF127143.1|AF127143 [5726290] gij3907597jgbjAF094575.11AF094575 [3907597] gil5712666|gblAF140784.1|AF140784 [5712666] gi50304251gblAF061748.21AF061748 [5030425] gil42185251emblAJ009639.1|SPAJ9639 [4218525] giJ49028 8 1 lembIAJ239004.1 ISPN239004 gil56165241gblAF169483.11AF169483 [5616524] [4902881] gil5579395|gblAF162656.11AF16 2 6 5 6 [5579395] gil500l7lOlgblAF112358.1IAF112358 [5001710] gil55793931gb|AF162655.1IAF162655 [5579393] gi500l690IgblAF106539.11AF106539 [5001690] gil5578890lemblAJ131985.1|SPN131985 gil497327l gbAF144420.11AF144420 [4973271] [5578890] gi4973269gblAF144419.1IAF144419 [4973269] gil5566442|gb|AF167442.11AF16 74 4 2 [5566442] gi4973267gbAF144418.11AF144418 [4973267] gil5459332lemblAJ243540.1 |EVE243540 gi 4 9 28 190gbAF129757.1IAF129757 [4928190] [5459332] gil4927743gblAF126061.11AF126061 [4927743] gil5305398|gblAF072811.11AF072811 [5305398] gi49277421gblAF126060.1 AF126060 [4927742] gil52959 2 1|emblAJ242698.1|SPN242698 gil49277411gbjAF126059.11AF126059 [4927741] [5295921] gi5952lmbA24671SPN242697 gil4495247lembAJ24O675. 1 ISPN240675 gi5295920 1 [4495247] [5295920] gil5295919emblAJ242696.1 SPN242696 gi4495245lembAJ240670.1 ISPN240670 [5295919] gil5295918lemb|AJ242695.1|SPN24 269 5 [4495243 [5295918] gil4583522gbAF140356.1AF140356 [4583522] gil4495 2 4 lembAJ240668.11SPN240668 gi45352gbIAl4OS6.[4495241] gil5231206|gblAF157826.1IAF157826 [5231206] gi4495239embAJ240667. 1 SPN240667 gig523152032gbAF157825.35AF157827 [5231203] [449[239] WO 00/32825 PCT/IB99/02040 417 gil4495237|emblAJ240666.11SPN240666 gi14495I89lembIAJ24O64O.1 SPN240640 [4495237] [4495189] gil4495235lemblAJ240665.1 SPN240665 gil4495187IemblAJ24O639. SPN240639 [4495235] [4495187] gil4495 23 3 |emblAJ240664. 1 ISPN240664 gij4495185lemb1AJ240638.1 ISPN240638 [4495233] [44951851 giJ4495231 emblAJ240663.1 |SPN240663 giJ4495183 lemblAJ240637. 1 ISPN240637 [4495231] [4495183] gil4495229emblAJ240662.1 ISPN240662 giJ4495181 1emb1AJ240636. ISPN240636 [4495229] [4495181] gil4495227|emblAJ24066 1.1 SPN240661 gil44951791emblAJ240635.1 SPN240635 [4495227] [44951791 gil4495225|embiAJ240660. 1 SPN240660 gil4495177IemblAJ240634. 1 SPN240634 [4495225] [4495177] gil449522 3 |emblAJ240659. I|SPN240659 gil44951751emb1AJ240633.1 ISPN240633 [4495223] [4495175] gil4 4 9 5 22 1 emblAJ240658. 1 ISPN240658 gil4495173lembIAJ24O63O.1 ISPN240630 [4495221] [4495173] gil4 4 9 5 2 19|emblAJ240657.1 ISPN240657 giJ4495171 lemb1AJ240629.1 ISPN240629 [4495219] [4495171] gil4495 2 17lemblAJ240656. 1 SPN240656 gil44951691emb1AJ240628.1 ISPN240628 [4495217] [4495169] gil4495215|emblAJ240655.1 I|SPN240655 gij44951671emb1AJ240627.1 ISPN240627 [4495215] [4495167] gil4495 2 13lemblAJ240654. 1 SPN240654 gil4495165 emblAJ240626. 1 ISPN240626 [4495213] [4495165] gi44952 11 IemblAJ240653.1 |SPN240653 gil44951631emb1AJ240625. 1 ISPN240625 [4495211] [4495163] gil4495209|emblAJ240652.1 [SPN240652 giJ4 4 95161 1emb1AJ240624.1 SPN240624 [4495209] [4495161] gil4495207[emblAJ24065 1.1 ISPN240651 gil4495159lemb AJ240623.1 ISPN240623 [4495207] [4495159] gil4495205|emblAJ240650.1 ISPN240650 gil4495157lemb1AJ240622.1 ISPN240622 [4495205] [4495157] gil4 4 95 2 03 emblAJ240649.1 |SPN240649 gil4495155lemb1AJ240621.1 ISPN240621 [4495203] [4495155] gil4495201 |emblAJ240648. 1 SPN240648 gil4495153IemblAJ240620. ISPN240620 [4495201] [4495153] gil4495199|emblAJ240647. I|SPN240647 giJ449515 IembIAJ24O619.1 ISPN240619 [4495199] [4495151] gil4495197IemblAJ240644. 1 |SPN240644 gil44951491emblAJ240616.1 SPN240616 [4495197] [4495149] gil4495195|emblAJ240643. 1 1SPN240643 gil4495I471emb1AJ240615.1 ISPN240615 [4495195] [4495147] gil4 4 95193|emblAJ240642.1|SPN240642 gil4495 lembIAJ24O614.1 ISPN240614 [4495193] [4495145] gij4495191 emb[AJ24064 1.1 |SPN240641 giJ4495143 lembIAJ240613.1 ISPN240613 [4495191] [4495143] WO 00/32825 PCT/IB99/02040 418 gil4495141|emblAJ240612.11SPN240612 giI4538797lembjAJ24O78 1.1 SPN24078I [4495141] [4538797] gil4495139|embiAJ240611.1 ISPN240611 gil45387941emb1AJ240780.1 ISPN240780 [4495139] [4538794] gil4495137|emblAJ2406 10.1 ISPN2406 10 giJ453879 1 lemb1AJ240779. 1 SPN240779 [4495137] [4538791] gil4495135|emblAJ240609. 1| SPN240609 gil4538788lembiAJ240778.1 SPN240778 [4495135] [4538788] gil4495133|emblAJ240608. I SPN240608 gil45387851emb1AJ240777. 1 ISPN240777 [4495133] [4538785] giJ449513 IemblAJ240607. I|SPN240607 gil4538782lemblAJ240776.1 ISPN240776 [4495131] [4538782] gil4495129|emblAJ240606.1 ISPN240606 gil4538779lemblAJ240775.1 ISPN240775 [4495129] [4538779] gil4883698|gblAF079807.11AF079807 [4883698] gil4538776jemb1AJ240774.1 SPN240774 gil48385621gbjAF145055. 1lAF145055 [4838562] [4538776] gil40637271gb[L29324.11STRINTE [4063727] gil4538773lemblAJ240773 1 SPN240773 gi146377jgbL2924.[4538773] gil3093401lemblAJ005619.1|SPAJ5619 [3093401] gil4538770cmbAJ240772.1 ISPN240772 gil4103889|gblAF029368.11AF029368 [4103889] [4538770] gil2897689|dbj|D63805.1|D63805 [2897689] gij4538767lemblAJ240771.11SPN240771 gil4566771|gblAF117741.1|AF117741 [4566771] [4538767] gil45667681gblAF117740.1IAF117740 [4566768] [4538764 gil4538836|emblAJ240793. I|SPN240793 giJ4538761 lemb1AJ240769. ISPN240769 [4538836] [4538761] gil4538832|emblAJ240792.1 ISPN240792 gil45387581emblAJ240768 ISPN240768 [4538832] [4538758] gil4538828|emblAJ24079 1.1 [SPN240791 gij45387551emb1AJ240767.1 ISPN240767 [4538828] [4538755] gil4538824lemblAJ240790. 1 lSPN240790 gi4538752lemb1AJ240766. 1 ISPN240766 [4538824] [4538752] gil45388 2 1 |emblAJ240789. 1 ISPN240789 gil4538749emblAJ240765. 1 ISPN240765 [4538821] [4538749] gil4538818|emblAJ240788.1 [SPN240788 gil4538746lemblAJ24076 1.1 ISPN240761 [4538818] [4538746] gil4538815|emblAJ240787.1 |SPN240787 giJ4538743IembIAJ24O76O. ISPN240760 [4538815] [4538743] gil4538812emblAJ240786. 1 SPN240786 gil4538740lemb1AJ240759 ISPN240759 [4538812] [4538740] gil4538809|emblAJ240785. 1 |SPN240785 gi45387371emblAJ240758.1 SPN240758 [4538809] [4538737] gil4538806lemblAJ240784. 1 SPN240784 gi4538734lembAJ240757.1 SPN240757 [4538806] [4538734] gil4538803lemblAJ240783.1|ISPN240783 [4538803] N2783gi453873 1 emblAJ240756.1 ISPN240756 [4538731] gil4538800lemblAJ240782. I SPN240782 gil4538728lemblAJ240755.1 SPN240755 [4538800] [4538728] WO 00/32825 PCT/IB99/02040 419 gil4538725|emblAJ240754.1SPN240754 giJ4519233ldbjIABO1 1207.1JAB0I 1207 [4519233] [4538725] giJ451923I dbj AB0 1206.1IAB0 1206 [4519231] gil4538722|emblAJ240753.1 I|SPN240753 gil4519229ldbjlABO11205.1IABOl1205 [4519229] [4538722] gil4538719|emblAJ240752.1 ISPN240752 gil45I9227IdbjIABOl 1204.1 ABOl 1204 [4519227] [4538719] gil4519225dbjlABOl1203.1ABOI1203 [4519225] gil4538716|emblAJ24075 1.1 ISPN240751 giJ45l9223IdbjABO 1202.1IABO 1202 [4519223] [4538716] giJ45192211dbjAB011201.1ABO11201 [4519221] giJ4538713|emblAJ240750. 11 SPN240750 gi45192 ldbjIABO 1200.1 IABO 1200 [4519219] [4538713] gil4538710[emb|AJ240749. 1 SPN240749 gil45192 ldbjABO 1199.1 ABO 1199 [4519217] [4538710] gil45l92ISldbjlABOll198.11AB011198 [4519215] gil45387071emblAJ240748. I|SPN240748 gi44951271emb1AJ240605. ISPN240605 [4538707] [4495127] gil4538704|emblAJ240747. 1 SPN240747 gi446803 1 embIAJ132957. ISPN132957 [4538704] [4468031] giJ4538701 [emblAJ240746. 1| SPN240746 gi4468029embAJ132956.1 ISPN132956 [4538701] [4468029] gil4538698lemblAJ240745. I|SPN240745 gil4218532IembAJO10312.1 SPNO10312 [4538698] [4218532] gi14538695lemblAJ240744.1 [SPN240744 gi4456852emblAJ236792.1 SPN236792 [4538695] [4456852] gil4538692|emblAJ240743.1 ISPN240743 gil44568501emblAJ23679 1.1 SPN236791 [4538692] [4456850] gil4538689|emblAJ240742. 1 |SPN240742 gi4456848lembAJ236790.1 ISPN236790 [4538689] [4456848] gil4538686|emb|AJ24074 1.1 |SPN240741 gil4456846lembjAJ236789.1 ISPN236789 [4538686] [4456846] gil453 8 6 8 3|emblAJ240740.1 ISPN240740 gi3550644emblAJ006987.11SPAJ6987 [3550644] [4538683] gi3550625lembAJ006986.1 SPAJ6986 [3550625] gil4538680lemblAJ240739. 1 ISPN240739 gil44165181gbAF014458.2AF014458 [4416518] [4538680] gil4538677|emblAJ240738.1|SPN240738 gil44O626OIgblAF105116.1IAF105116 [4406260] [4538677] gi144062571gbAF1OS115.IIAF1OS115 [4406257] gil4530444|gb|AF118229.1|AF118229 [4530444] gij44O62S41gblAFlOSI14.11AF1OS114 [4406254] gil4519253|dbj|AB015852.1|AB015852 [4519253] gil44062461gbAFIOS113.1AF1OS1I3 [4406246] gil4519251ldbjlABO15851.1IABO15851 [4519251] gi44062431gbAF1OS112.1IAFIOS112 [4406243] gil4519249|dbjlAB015850.1IABO15850 [4519249] gi4138533embAJOOS815.1 SPN5815 [4138533] gil4519247|dbjABO15849.1|ABO15849 [4519247] gi138217261embAJ232433.1 SPN232433 gil4519245|dbj|ABO15848.1|AB015848 [4519245] [3821726] gil4519243ldbj|AB015847.1IABO15847 [4519243] gil38217241emb1AJ232432.1jSPN232432 [3821724] gil4519241ldbj|AB015846.llAB015846 [4519241] giI4 1941 dbiAB~S84. 1 AB~ 586 [51941]gi3821722jernb1AJ23243 1.1 1SPN232431gil4519239Idbj|AB01 1210.1|ABOI 1210 [4519239] [3821722] gil4519237|dbjIABO11209.1IABO11209 [4519237] gi3821720lemb1AJ232430.1 SPN232430 gig4519235idbj4AB5 d1208.1bABOj 1208 [4519235] [3821720] WO 00/32825 PCT/IB99/02040 420 gil3821718|emblAJ232429.1|SPN232429 gil3821670IemblAJ232405. 1 SPN232405 [3821718] [3821670] gil3821716|emblAJ232428. 1| SPN232428 gil3821668lemblAJ232404.1 ISPN232404 [3821716] [3821668] gil3821714lemb|AJ232427. I|SPN232427 gil3821666|emblAJ232403.1 ISPN232403 [3821714] [3821666] gil3821712|emblAJ232426. 1 ISPN232426 gil3821664|emblAJ232402. 1 SPN232402 [3821712] [3821664] gil3821710IemblAJ232425. I|SPN232425 gil3821662|emblAJ23240 1.1 SPN232401 [3821710] [3821662] gil3821708|emblAJ232424.1 ISPN232424 gil3821660|emblAJ232399. 1 SPN232399 [3821708] [3821660] gil3821706lemblAJ232423.1 |SPN232423 gil3821658|emblAJ232398.1 |SPN232398 [3821706] [3821658] gil3821704|emblAJ232422. 1 SPN232422 gil38216561emblAJ232397. I|SPN232397 [3821704] [3821656] gil3821702IemblAJ23242 1.1 ISPN232421 gil3821654|emb|AJ232396. 1 |SPN232396 [3821702] [3821654] gil3821700|emb|AJ232420. 1 SPN232420 gil38216521emblAJ232395.1 ISPN232395 [3821700] [3821652] gil3821698|emblAJ232419.1 ISPN232419 gil3821650|emb|AJ232394. 1 SPN232394 [3821698] [3821650] gil38216961emblAJ232418.1 ISPN232418 gil3821648lemblAJ232393. I|SPN232393 [3821696] [3821648] gil3821694|emblAJ232417.1 |SPN232417 gil3821646|emblAJ232392. 1 SPN232392 [3821694] [3821646] gil38216921emb|AJ232416.1 ISPN232416 gil3821644lemblAJ23239 1.1 |SPN232391 [3821692] [3821644] gi13821690lemblAJ232415.1 |SPN232415 gil3821642|emblAJ232390. 1 |SPN232390 [3821690] [3821642] gil3821688|emblAJ232414.1 SPN232414 gil3821640IemblAJ232389.1 ISPN232389 [38216881 [3821640] gil3821686|emblAJ232413.1ISPN232413 gil3821638|emb|AJ232388.1|SPN232388 [3821686] [3821638] gil3821684|emblAJ232412.1 |SPN232412 gil3821636|emblAJ232387. I|SPN232387 [3821684] [3821636] gil38216821emblAJ23241 1.11SPN232411 gil3821634|emblAJ232386.11SPN232386 [3821682] [3821634] gil3821680|emblAJ232410.11SPN232410 gil3821632lemblAJ232385.I|SPN232385 [3821680] [3821632] gil3821678lemblAJ232409. I|SPN232409 gil3821630|emblAJ232384.1 |SPN232384 [3821678] [3821630] gil3821676|emblAJ232408. 1 ISPN232408 gil3821628|emblAJ232383. I 1SPN2323 83 [3821676] [3821628] gil3821674lemb|AJ232407. 1 SPN232407 gil3821626lemblAJ232382.1 SPN232382 [3821674] [3821626] gil3821672jemblAJ232406.1 ISPN232406 gil3821624|emblAJ23238 1.1 |SPN232381 [3821672] [3821624] WO 00/32825 PCT/IB99/02040 421 gil3821622lemblAJ232380. 1 SPN232380 gil3821576lembjAJ232356.11SPN232356 [3821622] [3821576] gil3821620|emblAJ232379.1 |SPN232379 gil38215741emb1AJ232355. ISPN232355 [3821620] [3821574] gil3821618lemblAJ232378.1 ISPN232378 gil38215721emblAJ232353.1 ISPN232353 [3821618] [3821572] gil3821616emblAJ232377.1 |SPN232377 gi138 2 1570lemblAJ232352.1 ISPN232352 [3821616] [3821570] gil3821614lembIAJ232376. 1 SPN232376 gij3821568IemblAJ23235 1.1 ISPN232351 [3821614] [3821568] gil38 2 16121emblAJ232375. 1 SPN232375 gil382l566lemb1AJ232350.1 ISPN232350 [3821612] [3821566] gil3 82 1610|emblAJ232373. 1 ISPN232373 gil3821564lemb1AJ232349.1 SPN232349 [3821610] [3821564] gil3821608lemblAJ232372. 1 lSPN232372 gil38 2 l562lemb1AJ232348.1 SPN232348 [3821608] [3821562] gil3821606|emblAJ23237 1.1 ISPN232371 gi1382l5601emb1AJ232347.1 SPN232347 [3821606] [3821560] gil38 2 1604|emblAJ232370. 1 SPN232370 gi13821558jemblAJ232346. 1 ISPN232346 [3821604] [3821558] gil3821602lemblAJ232369. 1 lSPN232369 gil3821556lemblAJ232345.1 SPN232345 [3821602] [3821556] gil3 8 2 1600[emblAJ232368.1 ISPN232368 gi138215541emblA3232344.1 ISPN232344 [3821600] [3821554] gil3 82 1598emblAJ232367.1 SPN232367 gil3821552lembIAJ232343.1 SPN232343 [3821598] [3821552] gil3821596|emblAJ232366. I|SPN232366 gil38215501emblAJ232342. 1 JSPN232342 [3821596] [3821550] gil38 2 1594|emblAJ232365.1 |SPN232365 gi1382l5481emblA323234 1.1 ISPN232341 [3821594] [3821548] gil3820454|emb[AJ007367.11SPN7367 [3820454] gil38215461emblA3232340.1 ISPN232340 gil3 8 2 15921emblAJ232364. 11SPN232364 [3821546] [3821592] gil382l5441emblA3232339. 1 ISPN232339 gil3821590lemblAJ232363.1ISPN 23 2 3 6 3 [3821544] [3821590] gi38 2 l5421emblAJ232338.1 ISPN232338 gil3821588|emblAJ232362. 1 SPN232362 [3821542] [3821588] gil38215401emblAJ232337.1 SPN232337 gil3821586jemblAJ23236 1.1 SPN232361 [3821540] [3821586] gil38 2 15381emb1AJ232336.1 SPN232336 gil3821584lemblAJ232360.1 |SPN232360 [3821538] [3821584] gil38215361emb1AJ232335.1 ISPN232335 gil3821582emblAJ232359.1SPN232359[3821536] [i3821582ebA225.11P225 gil3821534lemblAJ232334. I SPN232334 [3821582] gil3821580lemblAJ232358.1ISPN23235 8 [3821534] [3821580] gi3821532bembAAJ232333.11SPN232333 gil3821 578embgAJ232357.1lSPN232357 [3821532] [3821578] gil3821530embAJ232332.1 ISPN232332 [3821530] WO 00/32825 PCT/IB99/02040 422 gil3821528|emblAJ232331.1|SPN232331 gil3821480|emblAJ232306.11SPN232306 [3821528] [3821480] gil3821526|emblAJ232330. 1| SPN232330 gil3821478lemblAJ232305.1 SPN232305 [3821526] [3821478] gil3821524|emblAJ232329.1 ISPN232329 gil3821476lemblAJ232304. ISPN232304 [3821524] [3821476] gil3821522|emblAJ232328. 1 SPN232328 gil3821474|emblAJ232303.1 SPN232303 [3821522] [3821474] gil3821520lemblAJ232327. 1 ISPN232327 gil3821472|emblAJ232302. 1 ISPN232302 [3821520] [3821472] gil3821518|emblAJ232326.1 |SPN232326 gil3821470|emblAJ232301.1 |SPN232301 [3821518] [3821470] gil3821516|emblAJ232325. 1 ISPN232325 gil3821468|emblAJ232300. I|SPN232300 [3821516] [3821468] gil3821514|emblAJ232324. 1 ISPN232324 gil3821466|emblAJ232299. I|SPN232299 [3821514] [3821466] gil3821512IemblAJ232322.1 |SPN232322 gil3821464IemblAJ232298. 1 SPN232298 [3821512] [3821464] giJ38215 10|emblAJ232321.1 SPN232321 gil38214621emblAJ232297.1 |SPN232297 [3821510] [3821462] gil3821508lemblAJ232320. 1 SPN232320 gil3821460IemblAJ232295. I|SPN232295 [3821508] [3821460] gil3821506lemblAJ232319.1 |SPN232319 gil3821458|emblAJ232294.1 |SPN232294 [3821506] [3821458] gil38215041emblAJ232318.1 |SPN232318 gil3821456|emblAJ232293. 1 |SPN232293 [3821504] [3821456] gil3821502lemblAJ232317.1 |SPN232317 gil3821454|emblAJ232292. 1 SPN232292 [3821502] [3821454] gil3821500IemblAJ232316.1 SPN232316 gil3821452|emb|AJ23229 1.1 |SPN232291 [3821500] [3821452] gil3821498lemblAJ232315.1 ISPN232315 gil3821450|emblAJ232290.1 |SPN232290 [3821498] [3821450] gil3821496emblAJ232314.1 1SPN232314 gil3821448|emblAJ232289.1 |SPN232289 [3821496] [3821448] gil38214941emblAJ232313.1 |SPN232313 gil3821446|emblAJ232288.1 ISPN232288 [3821494] [3821446] gil3821492|emblAJ232312.1|SPN232312 gil3821444lemblAJ232287. I|SPN232287 [3821492] [3821444] gil3821490|emblAJ2323 11.1 ISPN232311 gil3821442|emblAJ232286. I|SPN232286 [3821490] [38214421 gi13821488lemblAJ2323 10.1 SPN2323 10 gil3821440|emblAJ232285.1 ISPN232285 [3821488] [3821440] gil3821486|emblAJ232309.1 |SPN232309 gil3821438|emblAJ232284.1 |SPN232284 [3821486] [3821438] gil3821484|emblAJ232308.1 |SPN232308 gil3821436|emb|AJ232283.1 [SPN232283 [3821484] [3821436] gil3821482|emblAJ232307.1 [SPN232307 gil3821434|emblAJ232282.1 ISPN232282 [3821482] [3821434] WO 00/32825 PCT/IB99/02040 423 gil3821432|emblAJ232281.1|SPN232281 gi13821384leiblAJ232256.1 SPN232256 [3821432] [3821384] gil3821430lemblAJ232280. 1 SPN232280 gij3821382lemblAJ232255.1 ISPN232255 [3821430] [3821382] gil3821428lemblAJ232279. 1 SPN232279 gil3821380lemblAJ232254. ISPN232254 [3821428] [3821380] gil3821426|emb|AJ232278.1 ISPN232278 gij3821378lemb1AJ232253.1 SPN232253 [3821426] [3821378] gil3821424lemblAJ232276. 1 |SPN232276 gi13821376jemblAJ232252.1 SPN232252 [3821424] [3821376] gil3821422lemblAJ232275. 1 SPN232275 gil3821374lemblAJ23225 1.1 SPN232251 [3821422] [3821374] gil3821420|emblAJ232274.1 ISPN232274 gil3821372lemblAJ232250.1 ISPN232250 [3821420] [3821372] gil3821418lemblAJ232273.1 SPN232273 gil38213701emblAJ232249.1 ISPN232249 [3821418] [3821370] gil3821416|emb|AJ232272. 1 ISPN232272 gil38213671emb1A3232248.1 SPN232248 [3821416] [3821367] gil3821414|emblAJ232271.1 |SPN232271 gi13821365lemb1AJ232247. 1 ISPN232247 [3821414] [3821365] gil38 2 1412lemblAJ232270.1 |SPN232270 gil3821363lemblAJ232246.1 ISPN232246 [3821412] [3821363] gil3821410lemb|AJ232269. 1 |SPN232269 giJ3821361 emblAJ232245.1 ISPN232245 [3821410] [3821361] gil3821408|emblAJ232268. 1 ISPN232268 gil3821359lemblAJ232244.1 ISPN232244 [3821408] [3821359] gil3821406|emblAJ232267.1 ISPN232267 gij38213571emb1AJ232243. ISPN232243 [3821406] [3821357] gil3821404|emblAJ232266.1 ISPN232266 gi13821355lemblAJ23224 1.1 ISPN232241 [3821404] [3821355] gil3821402|emblAJ232265. 1 SPN232265 gil29218421gblAF047385.11AF047385 [2921842] [3821402] gil29098631gbjAF047696.11AF047696 [2909863] gil3821400|emb|AJ232264.1 |SPN232264 gij41933531gblAF055088.11AF055088 [4193353] [3821400] gil3821398|emblAJ232263.1ISPN232263 gil41852421gbIAH007276. 1 ISEGSPTNJUNC [3821398] [4185242] gil38 2 1396lemblAJ232262. I|SPN232262 [4185241 [3821396] gil3821394lemblAJ232261.1 |SPN232261 [48524] [3821394] gil3821392lemblAJ232260. 1 |SPN232260 gil40979791gbIU72655.11SPU72655 [4097979] [3821392] gi14063720igb1L29323.1 STRMTR [4063720] gil3 82 1390emblAJ232259. I|SPN232259 gill 657605igbIU66846.1 ISPU66846 [1657605] [3821390] [3821390]gil 1 6576021gbIU66845. 1 ISPU6684541657602] gi13821388lemblAJ232258. 1 ISPN232258 gil40094851gblAF068903.11AF068903 [4009485] [3821388] gil3821386|emblAJ232257. I|SPN232257 gil40094771gblAF068902.11AF068902 [4009477] [3821386] gil40094621gblAF068901.1AF068901 [4009462] WO 00/32825 PCT/IB99/02040 424 gil3947767lemb|AJ233896.1 ISPN233896 gil1498294igb1U41735.1ISPU41735 [1498294] [3947767] gi112134931gbIU47687.11SPU47687 [1213493] gil3947765lemblAJ233895.1 |SPN233895 gil 11631091gbjU43526. 1 ISPU43526 [1163109] [3947765] gil3947763|emblAJ233894.1|SPN233 89 4 gil55600ljgbIU15171.11SPU15171 [556001] [3947763] gi455063jgb1U02920.11SPU02920 [455063] gil3947761 lemblAJ233893. 1| SPN233893 gil784896jgbIL36923.1ISTRSTRH [784896] [3947761] gil33203861gblAF030373.11AF030373 [3320386] gil3947759lemb|AJ233892. I|SPN233892 gil28047721gblAF030374.11AF030374 [2804772] [3947759] gil3947757lemb1AJ23389 1.1 ISPN233891 gil28047621gblAF030372.1 AF030372 [2804762] [3947757] gil28047561gblAF030371.11AF030371 [2804756] gil3947755lemb|AJ233890.1 ISPN233890 gil28047501gblAF030370. IAF030370 [2804750] [3947755] gil28047451gblAF030369.11AF030369 [2804745] gil3947753lemblAJ233889.1 ISPN233889 gil28047391gblAF030368.11AF030368 [2804739] [3947753] gil3947 7 5 1 lemblAJ233888.1 |SPN233888 gij2804732lgblAF030367.11AF030367 [2804732] [3947751] gil2804726jgblAF030366.11AF030366 [2804726] gil3947749lemblAJ233887. 1 lSPN233887 gil2804720lgblAF030365.11AF030365 [2804720] [3947749] gij28047131gblAF030364.11AF030364 [2804713] gil3947730|emblAJ233886.11SPN233886 gil28047071gblAF03036311AF030363 [2804707] [3947730] gil37588 9 1lemblZ71552.1|SPADCA [3758891] gil280 4 7 0 l gbAF030362.11AF030362 [2804701] gil3818479|gblAF057294.11AF057294 [3818479] gil28046941gblAF030361.11AF030361 [2804694] gil23517671gblU89711.11SPU89711 [2351767] gij2804688lgblAF030360.11AF030360 [2804688] gil3395 6 6 1ldbj|ABOO6879.11AB006879 [3395661] gil28046821gblAF030359.11AF030359 [2804682] gil3395659ldbjlAB006878.11AB006878 [3395659] gij35O979ldbjlABOlO387.11AB010387 [3550979] gil3395657|dbj|AB006877.lAB006877 [3395657] gi2275 1 O0lemblAJOOO336.11 SPR6LDH [2275100] gil3395655ldbjlAB006876. 1 |AB006876 [3395655] gil3551853gbAF076029.11AF076029 [3551853] gij3395653ldbj|AB006875.11AB006875 [3395653] gil3551773gbU94770.11SPU94770 [3551773] gil3395651ldbjlABOO6874.11AB006874 [3395651] gil3550617lembiAJ004869.1 SPAJ4869 [3550617] gil3395649|dbjlAB006873.11AB006873 [3395649] gil3s135631gbIAF055727.11AF055727 [3513563] gil3395647|dbjlAB006872.1|AB006872 [3395647] gil35135611gblAF055726.11AF055726 [3513561] gil3395645ldbjlAB006871.1|AB006871 [3395645] gij35135591gblAF055725.11AF055725 [3513559] gil33956 4 3|dbjlABOO6870.11AB006870 [3395643] gil35135571gblAF055724.11AF055724 [3513557] gil33956 4 1ldbjIABOO6869. 1AB006869 [3395641] gi135 1gblAFOSS723.11AF055723 [3513555] gil3395639ldbjlAB006868.11AB006868 [3395639] gil3513553jgblAFO5S722.11AF055722 [3513553] gil23159921gblU87092.1|SPU87092 [2315992] gil3513549gbIAFOSS72l.11AF055721 [3513549] gil2209338|gbIU93576.11SPU93576 [2209338] gi135135451gblAF055720.11AF055720 [3513545] gil2109442|gb|AF000658. I|SPDNAARG gi119148691embIZ82001.11SPZ82001 t-19148691 [2109442] gi129114211gbAF046238.1lAF0462-8 [2911421] gil18815381gbIU09239.11SPU09239 [1881538] giI29l14191gblAF046237.11AF046237 [2911419] gil16669041gblU76218.1|SPU76218 [1666904] gil2911417jgbIAF046236.11AF046236 [2911417] gi116137661gbIU33315.11SPU33315 [1613766] gi2911415gbAF046235.1 AF046235 [2911415] WO 00/32825 PCT/IB99/02040 425 gil29114131gblAF046234. 1AF046234 [2911413] gil27659921emblZ99825. 1SPZ99825 [2765992] gil2911411 IgblAF046233. I|AF046233 [2911411] gil2765990|emb[Z99824.11SPZ99824 [2765990] gil2911409|gblAF046232.11AF046232 [2911409] gil2765988|emblZ99823.1lSPZ99823 [2765988] gil2911407|gblAF046231.1 1AF046231 [2911407] gil2765986|emblZ99822.I|SPZ99822 [2765986] gil2911405|gblAF046230.1|AF046230 [2911405] gil2765984|emblZ99821.11SPZ99821 [2765984] gil3258601|gblU40786.1|SPU40786 [3258601] gil2765982|emblZ99820.1|SPZ99820 [2765982] gil3211756|gblAF052209.11AF052209 [3211756] gil2765980|embIZ99819.1|SPZ99819 [2765980] gil3211752|gblAF052208.11AF052208 [3211752] gil2765978lembIZ99818.11SPZ99818 [2765978] gil32117471gblAF052207.1|AF052207 [3211747] gil2765976|emblZ99817.11SPZ99817 [2765976] gil3220194|gb}AF053121.1 IAF053121 [3220194] gil2765974|emblZ99816.1|SPZ99816 [2765974] gil2766052|embIZ99863.llSPZ99863 [2766052] gil2765972lembIZ99815.1 SPZ99815 [2765972] gil2766050|embIZ99862.1|SPZ99862 [2766050] gil2765970emblZ99814.11SPZ99814 [2765970] gil2766048|embIZ99861.11SPZ99861 [2766048] gil2765968|emb1Z99813.1|SPZ99813 [2765968] gil2766046|embIZ99860.11SPZ99860 [2766046] gil2765966|emblZ99812.1 SPZ99812 [2765966] gil2766044emb1Z99859. 1SPZ99859 [2766044] gil2765964|embIZ99811.11SPZ99811 [2765964] gil2766042|emblZ99858.1|SPZ99858 [2766042] gil2765962|embIZ99810.11SPZ99810 [2765962] gil2766040|emblZ99857.1|SPZ99857 [2766040] gil2765960|emblZ99809.11SPZ99809 [2765960] gil2766038jembIZ99856.11SPZ99856 [2766038] gil2765958|emblZ99808.1|SPZ99808 [2765958] gil2766036lemblZ99855. 1SPZ99855 [2766036] gil27659561embjZ99807.1|SPZ99807 [2765956] gil2766034|emblZ99854.1|SPZ99854 [2766034] gil2765954|embjZ99806.11SPZ99806 [2765954] gil2766032|emb1Z99853.1|SPZ99853 [2766032] gil2765952|emb|Z99805.IlSPZ99805 [2765952] gil2766030|emblZ99852.1SPZ99852 [2766030] gil2765950|embjZ99804.11SPZ99804 [2765950] gil2766028|emblZ99851.11SPZ99851 [2766028] gil2765948|emblZ99803.11SPZ99803 [2765948] gil2766026|embIZ99850.11SPZ99850 [2766026] gil28941041emblX77249.1|SPR6CIARH [2894104] gil2766024lemblZ99849.11SPZ99849 [2766024] gil3153897|gblAF067128.1|AF067128 [3153897] gil2766022|emblZ99848.11SPZ99848 [2766022] gil3152712|gblAF065153.1|AF065153 [3152712] gil2766020|emblZ99847.11SPZ99847 [2766020] gil315271OIgblAF065152.11AF065152 [3152710] gil2766018|embZ99846.11SPZ99846 [2766018] gil3152708|gb|AF065151.1|AF065151 [3152708] gil2766016|embjZ99845.1SPZ99845 [2766016] gil31164261gblU84387.I|SPU84387 [3116426] gil2766014|emblZ99844.11SPZ99844 [2766014] gil2385403lemblAJO01247.1 SP7465RR3 gil2766012|embZ99843.11SPZ99843 [2766012] [2385403] gil2766010|embIZ99842.1SPZ99842 [2766010] 2342540emblAJ001250.1|SP7978RR5 gil2766008|embIZ99841.1|SPZ99841 [2766008] gi|2342539|emblAJ001251.1|SP7978RR3 gil2766006|embIZ99840.1|SPZ99840 [2766006] [2342539] gil2766004|emblZ99839.11SPZ99839 [2766004] gil2342538|emblAJ001248.1|SP7466RR5 gil2766002|emb1Z99838.11SPZ99838 [2766002] [2342538] gil2766000|embIZ99837.11SPZ99837 [2766000] 2342537emblAJ001249.1|SP7466RRT gil2765998emblZ99828.1SPZ99828 [2765998] gil30658961gblAF058920.I1AF058920 [3065896] gil2765996|emblZ99827.1|SPZ99827 [2765996] gi 2982647|emblAJ002294.1|SPAJ2294 [2982647] gil2765994|emb1Z99826.1|SPZ99826 [2765994] WO 00/32825 PCT/IB99/02040 426 gil2982645lemblAJ002293.1ISPAJ2293 [2982645] gi12766116lemblZ99895. 1 SPZ99895 [27661161 gil2982643lemblAJ002292.1[SPAJ2292 [2982643] gil27661141emblZ99894.I1SPZ99894 [2766114] gil2982641 lemblAJO0229 1.1 ISPAJ2291 [2982641] gil27661121embIZ99893.11SPZ99893 [2766112] gil1620466|emblX99400.1ISPDACAO [1620466] gil27661 10lemblZ99892. 1 ISPZ99892 [2766110] gil2196665lemblZ84381.11HSZ84381 [2196665] gil2766I08lemblZ99891.11SPZ99891 [2766108] gil2196663lemblZ84380.11HSZ84380 [2196663] gil2766106lemblZ99890. 1 ISPZ99890 [2766106] gil2196661lemblZ84379.11HSZ84379 [2196661] gil2766104lemblZ99889.11SPZ99889 [27661041 gil2196659lemb1Z84378.I|HSZ84378 [2196659] gil2766102lemblZ99888.11SPZ99888 [2766102] gil625175|gblL36131.1lSTREXP10A [625175] gil2766100lembIZ99887.11SPZ99887 [2766100] gil30049451gblAF036624.11AF036624 [3004945] gi2766098lembIZ99886.11SPZ99886 [2766098] gil30 04 9 4 3 1gblAF036623.11AF036623 [3004943] gil2766096lembIZ99885.11SPZ99885 [2766096] gil3 0 04 9 4 1|gblAF036622.11AF036622 [3004941] gil2766094lembIZ99884.11SPZ99884 [2766094] gil30049391gblAF036621.11AF036621 [3004939] gil2766092lemblZ99883.11SPZ99883 [2766092] gil30049371gblAF036620.11AF036620 [3004937] gil2766090lemblZ99882.11SPZ99882 [2766090] gil3004935|gblAF036619.lAF036619 [3004935] gil2766088lembIZ99881.11SPZ99881 [2766088] gil2370572lembIZ86112.1|SPZ86112 [2370572] gij27660861embIZ99880.11SPZ99880 [2766086] gil2765946lemblZ99802.1|SPZ99802 [2765946] gil2766084lembIZ99879.11SPZ99879 [2766084] gil2398824|emblZ34303.1ISPCINREC [2398824] gil2766082lembIZ99878.11SPZ99878 [2766082] gil28 9 4 5 12|emblAJ223491.1|SPPPR3 [2894512] gil2766080lembIZ99877.11SPZ99877 [2766080] gil2198539|emblX85787.1ISPCPS14E [2198539] gil2766078lemblZ99876.11SPZ99876 [2766078] gil2766156lemblZ99915.1|SPZ99915 [2766156] gi12766076lembIZ99875.IISPZ99875 [2766076] gil2766154lemblZ99914.11SPZ99914 [2766154] gil2766074lemblZ99874.11SPZ99874 [2766074] gil2766152lemb|Z99913.1lSPZ99913 [2766152] gil2766072lembIZ99873.1 SPZ99873 [2766072] gil 2 7 66 150lemblZ99912.11SPZ99912 [2766150] gil2766070lemblZ99872.I1SPZ99872 [2766070] gil27 66 148lemb1Z99911.11SPZ99911 [2766148] gil2766068lembIZ99871.1 SPZ99871 [2766068] gil2766146lemblZ99910.11SPZ99910 [2766146] gil2766066lembIZ99870.11SPZ99870 [2766066] gil27 66 144lemb|Z99909.11SPZ99909 [2766144] gil2766064lembIZ99869. 1 ISPZ99869 [27660641 gil2766142lemblZ99908.11SPZ99908 [2766142] gij2766062lembIZ99868.11SPZ99868 [2766062] gil2766140|emblZ99907.11SPZ99907 [2766140] gil2766060lembIZ99867.1ISPZ99867 [2766060] gil2766138lemblZ99906.11SPZ99906 [2766138] gi12766058lemblZ99866.I1SPZ99866 [2766058] gil2766136lemblZ99905.1|SPZ99905 [2766136] gil2766056lembIZ99865.11SPZ99865 [2766056] gil27 6 6 134lemblZ99904.11SPZ99904 [2766134] gil2766054lembIZ99864.I SPZ99864 [2766054] gil2766132lemblZ99903.1|SPZ99903 [2766132] gil2765906lemblZ99206.I SPZ99206 [2765906] gil27 6 6 130lemb|Z99902.1SPZ99902 [2766130] gil2765904lembIZ99205.11SPZ99205 [2765904] gil2766128|emblZ99901.1|SPZ99901 [2766128] gil2765902lembIZ99204.11SPZ99204 [2765902] gil2766126lemblZ99900.11SPZ99900 [2766126] gij2765900jembIZ99203.11SPZ99203 [27659001 gil27 6 6 124lemblZ99899.1|SPZ99899 [2766124] gil2765898lembIZ99202.11SPZ99202 [2765898] gil27 6 6 122lemblZ99898.11SPZ99898 [2766122] gil2765896lembIZ99201.11SPZ99201 [2765896] gil2766120lemblZ99897.11SPZ99897 [2766120] gil2765894lemblZ99200.I SPZ99200 [2765894] gil27 6 6 1 181emb1Z99896. 1 ISPZ99896 [2766118] gil27086 3 11blAF3695.1S9AF036951 [2708631] WO 00/32825 PCT/IB99/02040 427 gil886956|emblZ49097.1|SPCS 11 12X [886956] gil 11612691gbIL39074. 1 STRSPXB [1161269] gil2656093|gb|L21856.1|STRMALR [2656093] gij 460093lemblX94909.I SPIGA1PRT [1460093] gil2576332lemblAJ002055.1|SPSPSA47 [2576332] gil17502631gbIU72720.11SPU72720 [1750263] gil2576330|emblAJ002054.1ISPSPSA2 [2576330] gil2986491gbIS56948.1 S56948 [298649] gil2511704lembIY10818.1ISPY10818 [25117041 gil245371gbIS43511.1 S43511 [254537] gil1944619lembIZ83335.1lSPZ83335 [1944619] gil2452271gbIS81051.1 S81051 [245227] gil24251081gblAF019904.1|AF019904 [2425108] gil2452261gbIS81045.1 S81045 [245226] gil2385404lemblAJO01246.1|SP7465RR5 gil2452251gbIS81043.1 S81043 [245225] [2385404] gil 150618lemblZ49988.1ISPMMSAGEN gil438213|embIZ16082.1IPNALIB [438213] [1150618] gil21496131gblU90721.1|SPU90721 [2149613] gil47456IembjXOI 138.1 ISPTN917A [47456] gil 4 9391lembIZ21841.1|SPPBP2BB [49391] gi11658316lemblZ47210.11SPDEXCAP [1658316] gil2209207|gblAF004325.11AF004325 [2209207] gill550802lemblX95385.1ISPCOMCGEN gil2293061lemblZ95914.1ISPZ95914 [2293061] [1550802] gil2276393|gblU16156.1ISPUI6156 [2276393] gil474S7IemblX0l 137.1 ISPTN917B [47457] gil2183314|gblAF003930.11AF003930 [2183314] gil9757l4lemblX9O941.1ISPTRJ5251 [975714] gil2182093lemblX95717.1|SPPARECGN gil9757l3lembX9O94O.11SPTLJ5251 [975713] [2182093] gil975709lemblX90939.1ISPDNATETM [975709] gil984230lemblZ49095. 1 ISPCS 111 1A [984230] gill524346lemblZ79691.1ISOORFS [1524346] gil886954lemblZ49096.1ISPCS1092X [886954] gill553054lemblX98364.11SPPBPHU9 [1553054] gill 181613ldbjlD82873.IISTRPBP2BE [1181613] gill553052lemblX98367.1ISPPBPHUI3 [1553052] gill 181612ldbjlD82871.IISTRPBP2BCZ gil1553050lembIX98366.11SPPBPHU12 [1553050] [1181612] gill553048lemblX98365.1ISPPBPHU1 [1553048] gill 181611 dbjlD82870.1ISTRPBP2BB2 [1181611] gil15750291gblU53509.1ISPU535O9 [1575029] gill 181579ldbjlD82869.1|STRPBP2BA1 [1181579] gil15429681gbIU49088.I1SPU49088 [1542968] gil 1181192ldbjlD82872. 1 ISTRPBP2BD [1181192] gil15429661gbIU49087.11SPU49087 [1542966] gil575595ldbjlD42075.1|STRPBP2B2 [575595] gil1536961lembIYO7845.11SPGYRA [1536961] gil1339971lidbjlD42074.1|STRPBP2B1 [1339971] gil47391lemblX16367.1ISPPBPX [47391] gil2108329lemblY1 1463.1|SPDNAGCPO gi11490398lembIZ67739.11SPPARCETP [1490398] [2108329] gil1944115ldbjlABOO2522.11AB002522 [1944115] [1490395 gil1666669lembIZ77727.1|SPIS1381C [1666669] gil1431589lembIZ74777.IISPTMRDHFR gil1666668lemblZ77726.1|SPIS1381B [1666668] [1431589] gil1666667lemblZ77725.1|SPIS1381A [1666667] gil4O8l45lembIZ21702.1ISPUNGMUTX [408145] gil1914873lembIZ82002.11SPZ82002 [1914873] gil47461 IembIX6lO25. ISPXISINT [47461 gil1431584lemblZ74778.1ISPDHFR [1431584] gil47459lemblX5S651.1ISPTNGG [47459] gil47452lemblZl 5120.1 |SPSTRG [47452] gil47454lembIX52632.1ISPT1545E [47454] gil581717lemblZ12159.IISPCP131G [581717] gil47421lembIZ7307.1[SPRECA [47421] gil47342lemblX17337.1ISPAMILOC [47342] gil474I9lemblX67873.1ISPPONA8 [47419] gil1800300|gbIU83667.11SPU83667 [1800300] gil47417lemblX67872.1ISPPONA7 [47417] gi1532066lemblY07780. 1ISPTETOGEN [1532066] gil47415lembX67871.1|SPPONA6 [47415] WO 00/32825 PCT/IB99/02040 428 gi147413lemblX67870.11SPPONA5 [47413] gil47331lemblX65133.1|SP577PBPX [47331] gil4741 1 lemblX67869. 1 ISPPONA4 [47411] gil559527lemblX65136.1 ISP 11OPBPX [559527] gil47409lemblX67867.1ISPPONA2 [47409] gil311415lemblZ22807.1|SP16SRNAA [311415] gil47407lemblX67866.1|SPPONA 1 [47407] gil47329lemblX65135.1|SP531PBPX [47329] gil47405|emblX67868.1|SPPNA3 [47405] gil47307lemb|X65131.1 ISP290PBPX [47307] gil47403lemb|X52474. 1 ISPPLY [47403] gil47295lemb|X58312.1|SP16SRNA [47295] gil984232|emblX16022.1|SPPENA [984232] gil854614lemblZ49109.1ISPGADAGN [854614] gil517190lemblX78215.1ISPPBPXG [517190] gil556428[gblL36660. 1ISTRORF1 [556428] gil295840lemblZ22230.1ISPPBP2BBA [295840] gil510621emblZ35135.1 ISPALIAG [511062] gil288981lemblZ22185.1ISPPBP2BAC [288981] gil12087371gbIU47625.11SPU47625 [1208737] gil288979lemblZ22184.11SPPBP2BAB [288979] gil5300621gblU12567.1|SPU12567 [530062] gil288466lemblZ21981.1ISPPBP2BAA [288466] gill53656|gb|M29686.1|STRHEXB [153656] gil49390lemblZ21813.11SPPBP2XD [49390] gil153654|gbIM18729.11STRHEXA [153654] gil49389lemblZ21812.11SPPBP2XC [49389] gill53608|gb|M14339.IISTRDPN2A [153608] gil49387lemblZ21811.1SPPBP2BJ [49387] gil153605|gblM14340.11STRDPN1A [153605] gil49385lemb|Z21810.1|SPPBP2BI [49385] gil643543|gblU20084.11SPU20084 [643543] gil49382lembIZ21808.1|SPPBP2BH [49382] gil643541|gblU20083.1|SPU20083 [643541] gil49380lemb|Z21807.1ISPPBP2BG [49380] gil643539|gblU20082.11SPU20082 [643539] gil49379iemblZ21806.1ISPPBP2BF [49379] gil643537|gblU20081.1|SPU20081 [643537] gil49377lemblZ21805.1|SPPBP2BE [49377] gil6435351gbIU20080.1|SPU20080 [643535] gil49376|emblZ21804.1|SPPBP2XB [49376] gil6435331gblU20079.11SPU20079 [643533] gil49375|emblZ21803.1|SPPBP2XA [49375] gil643531|gblU20078.11SPU20078 [643531] gil49374lemblZ21802.1|SPPBP2BD [49374] gil643529|gblU20077.1|SPU20077 [643529] gil49372lemblZ21801.1ISPPBP2BC [49372] gil643527|gblU20076.1ISPU20076 [643527] gil49369lemblZ21799.1ISPPBP2BA [49369] gil643525|gblU20075.1ISPU20075 [643525] gil47399lemblX13137.1ISPPENASE [47399] gil643523|gblU20074.11SPU20074 [643523] gil47397lemb|X13136.1ISPPENARE [47397] gil643521|gblU20073.11SPU20073 [643521] gill052802lemblX83917.1ISPGYRBG [1052802] gil643519|gblU20072.11SPU20072 [643519] gil587550|emblX72967.IISPNANA [587550] gil643517igblU20071.1|SPU20071 [6435171 gil49384lemblZ21809.1|SPPBP1AB [49384] gil643515|gblU20070.1|SPU20070 [643515] gil49371lemblZ21800.1|SPPBP1AA [49371] gil643513|gblU20069.1|SPU20069 [643513] gil984228lemblZ49094.1|SPCS1091A [984228] gil6435 11 |gblU20068. 1 [SPU20068 [643511] gil47372lemblX54225.1|SPENDA [47372] gil643509|gblU20067.11SPU20067 [643509] gil806590lembIZ49246.1ISP667SOD [806590] gil1017802|gblU37560.1lSPU37560 [1017802] gil407172|embjZ26851.1jSPATPAS2 [407172] gil663277|gblM36180.1ISTRCOMAA [663277] gil407166lemblZ26850.1|SPATPAS1 [407166] gil4377041gblL20670.1ISTRHYALURO [437704] gil47353lemblX63602.1ISPBOX [47353] gil1538491gbIL07751.11TRNTN5252R [153849] gil47348lemb|X05577.lISPAPHA3 [47348] gil153855igblM25519.1|STRVAI [153855] gil47337lemblX65132.1|SP824PBPX [47337] gil153853|gbIM80215.1|STRUVS402A [153853] gil47335lemblX65134.1ISP669PBPX [47335] gil153848|gb|L07750.1ISTRTN5252L [153848] WO 00/32825 PCT/IB99/02040 429 gil1538401gblM74122.1 ISTRSURPROA [153840] gil153796|gblM60763.1ISTRRRNAA [153796] gil153791|gblM31296.1|STRRECP [153791] gil516639|gb|L20556.1|STRPLPA [516639] gil153783|gblM28679.1|STRPROMB [153783] gi1153782|gbIM28678.1ISTRPROMA [153782] gil1537661gb|M90527.11STRPONA [153766] gil1537641gblJ04479.1|STRPOLA [153764] gil153752|gbIM25515.1ISTRNG4369 [153752] gill 537221gb|L0861 1.1 ISTRMLTODX [153722] gill53702|gblJ01796.1ISTRMALMXP [153702] gil153701IgbJO1795.1ISTRMALMX [153701] gil1536931gblM13812.1ISTRLYTPN [153693] gil153691|gblM17717.1|STRLYS [153691] gil1536671gbIM25525.IISTRKAG73 [153667] gil398102|gblL20564.1lSTREXP9B [398102] gil39810OIgblL20563.1ISTREXP9A [398100] gil398098|gb|L20562.1ISTREXP8A [398098] gil3980961gb|L20561.1ISTREXP7A [398096] gil3980941gblL20560.1|STREXP6A [398094] gil3980921gb|L20559.1ISTREXP5A [398092] gil398090lgb|L20558. 1 STREXP4A [398090] gil1536261gbIJ04234.11STREXOA [153626] gil153612lgb|M11226.1ISTRDPNM [153612] gil1536031gb[M25521.11STRDN87669 [153603] gil153601|gblM25526.1|STRDN87577 [153601] gil153599|gb|M25522.1|STRDN179 [153599] gi11535941gbIM37688.11STRDACA [153594] gi11535821gbjL07752.1ISTRATTB [153582] gi|466514|gb|L31413.1ISTR1RRA [466514] gil15355llgbIM25520.11STR8249 [153551] gi1153549|gblM25524.1|STR5313972 [153549] gi1153547|gbIM25517.11STR29044 [153547] gi1153545igbIM25523.11STR181071 [153545] gil153541IgblM25518.1ISTR121 [153541] gil 153539|gblM25516.1 ISTRI 10K70 [153539] gil506632gblU04047.1|SPU04047 [506632] gil393267|gbIL19055.1|STRPAPA [393267] gil4420661gblS62272.1|S62272 [442066] gil295191|gbIL15190.1ISTRPURISYN [295191]

Claims (95)

  1. 2. The method of claim 1, further comprising expressing a recombinant bacteriophage ORF in cells of a bacterial strain, wherein inhibition of said cells following expression of said ORF is indicative that said product is active on an 15 essential bacterial target.
  2. 3. The method of claim 2, wherein inhibition of said bacterium following expression of said ORF is determined by comparison with the growth or viability of said bacterium following expression of an inactivated mutant form of said ORF or in 20 the absence of expression of said ORF, and wherein inhibition of said bacterium following expression of said ORF is indicative that said product is active on an essential bacterial target.
  3. 4. The method of claim 2, wherein expression of said ORF is inducible. 25
  4. 5. The method of claim 1, further comprising sequencing at least a portion of a bacteriophage genome.
  5. 6. The method of claim 1, wherein at least a portion of the nucleotide 30 sequence of a bacteriophage genome is known, said method further comprising identifying at least one ORF in said portion by computer analysis of said sequence.
  6. 7. The method of claim 6, further comprising analyzing the sequence of said at least one ORF or of a polypeptide encoded by said ORF to identify 35 homologous genes or gene products of known biochemical function, thereby indicating the biochemical function of said polypeptide. WO 00/32825 PCT/IB99/02040 431
  7. 8. The method of claim 7, wherein said homologous gene or gene product is a bacterial gene important for cell viability.
  8. 9. The method of claim 7, wherein said homologous gene or gene product 5 is a gene or gene product known to have a bacteria-inhibiting function.
  9. 10. The method of claim 6, further comprising analyzing the sequence of said at least one ORF or of a polypeptide encoded by said ORF to identify structural motifs in said polypeptide, thereby indicating the cellular function of said polypeptide. 10
  10. 11. The method of claim 1, wherein a host bacterium for said bacteriophage is selected from the species group consisting of bacteria listed in Table 1. 15 12. The method of claim 1, wherein said bacteriophage is selected from the group consisting of uncharacterized bacteriophage listed in Table 1.
  11. 13. The method of claim 2, wherein a plurality of bacteriophage ORFs are expressed in at least one bacterium. 20
  12. 14. The method of claim 13, wherein each of said plurality of bacteriophage ORFs is expressed in a different bacterium.
  13. 15. The method of claim 14, wherein said plurality of bacteriophage ORFs 25 comprises at least 10% of the ORFs in the genome of said bacteriophage.
  14. 16. The method of claim 1, wherein said pathogenic bacterium is an animal pathogen. 30 17. The method of claim 16, wherein said pathogenic bacterium is a human pathogen.
  15. 18. The method of claim 1, wherein said pathogenic bacterium is a plant pathogen. 35
  16. 19. The method of claim 1, further comprising confirming the inhibitor function of said ORE. WO 00/32825 PCT/IB99/02040 432
  17. 20. The method of claim 19, wherein said confirming comprises expressing a loss-of-function mutant form of said ORF in said host bacterium. 5 21. The method of claim 1, wherein said identifying a nucleic acid sequence encoding a gene product active on an essential bacterial target comprises identifying a nucleic acid sequence encoding a homolog of a bacteriophage polypeptide known to be active on an essential bacterial target. 10 22. The method of claim 1, wherein said identifying a bacteriophage coding region comprises identifying a first coding region from a bacteriophage having a non-pathogenic host bacterial strain related to said pathogenic bacterium, said first coding region encoding a product active on an essential bacterial target; and identifying a homolog of said first coding region, wherein said 15 homolog is a probable said bacteriophage coding region encoding a product active on an essential bacterial target.
  18. 23. The method of claim 2, wherein a plurality of bacteriophage ORFs from a plurality of different bacteriophage are expressed in at least one bacterium. 20
  19. 24. The method of claim 23, wherein each of said plurality of bacteriophage ORFs are expressed in different bacteria. 25 25. A method for identifying a target for antibacterial agents, comprising determining the bacterial target of an uncharacterized bacteriophage inhibitor protein.
  20. 26. The method of claim 25, wherein said determining comprises identifying at least one bacterial protein which binds to said bacteriophage inhibitor 30 protein or a fragment thereof.
  21. 27. The method of claim 26, wherein said binding is determined using affinity chromatography on a solid matrix. 35 28. The method of claim 25, wherein said determining comprise& identifying at least one protein:protein interaction using a genetic screen. WO 00/32825 PCT/IB99/02040 433
  22. 29. The method of claim 28, wherein said genetic screen is a yeast two hybrid screen.
  23. 30. The method of claim 25, wherein said determining comprises a co 5 immunoprecipitation assay or a protein-protein crosslinking assay.
  24. 31. The method of claim 25, wherein said determining comprises identifying a mutated bacterial coding sequence which protects a bacterium from said bacteriophage inhibitor. 10
  25. 32. The method of claim 25, wherein said determining comprises identifying a bacterial coding sequence which protects a bacterium against said bacteriophage inhibitor when expressed at high levels in said bacterium. 15 33. The method of claim 25, wherein said determining further comprises identifying a bacterial nucleic acid sequence encoding a polypeptide target of said bacteriophage inhibitor protein.
  26. 34. The method of claim 33, wherein said nucleic acid sequence is 20 identified by determining at least a portion of the amino acid sequence of a bacterial protein target, and identifying a bacterial nucleic acid sequence which encodes said protein target.
  27. 35. The method of claim 25, wherein said bacterial target is naturally 25 produced by a bacterial species selected from the group consisting of species of the genera listed in Table 1.
  28. 36. The method of claim 25, wherein said bacterial target is naturally produced by a bacterial strain selected from the group consisting of species listed in 30 Table 1.
  29. 37. The method of claim 25, wherein said inhibitor protein is naturally produced by a bacteriophage selected from the group consisting of uncharacterized bacteriophage listed in Table 1. 35
  30. 38. The method of claim 25, further comprising identifying a bacteriophage ORF which encodes a product having a bacteria-inhibiting function. WO 00/32825 PCT/IB99/02040 434
  31. 39. The method of claim 38, wherein said identifying a phage ORF comprises expressing at least one bacteriophage ORF in a bacterium, wherein inhibition of said bacterium following said expression is indicative that said ORF 5 encodes a bacteria-inhibiting function.
  32. 40. The method of claim 39, wherein a plurality of bacteriophage ORFs are expressed in at least one bacterium. 10 41. The method of claim 40, wherein each of said plurality of bacteriophage ORFs is expressed in a different bacterium.
  33. 42. The method of claim 41, wherein said plurality of bacteriophage ORFs comprises at least 10% of the ORFs in the genome of said bacteriophage. 15
  34. 43. The method of claim 25, wherein said determining the bacterial target of a bacteriophage inhibitor protein is performed for a plurality of different bacteriophage of the same host bacterium. 20 44. The method of claim 25, wherein said bacterial target originates from an animal pathogen.
  35. 45. The method of claim 44, wherein said bacterial target is a gene homologous to a gene from an animal pathogen. 25
  36. 46. The method of claim 44, wherein said pathogen is a human pathogen.
  37. 47. The method of claim 25, wherein said bacterial target originates from a plant pathogen. 30
  38. 48. The method of claim 25, wherein said bacterial target is a gene homologous to a gene from a plant pathogen.
  39. 49. The method of claim 25, further comprising determining the cellular or . 35 biochemical function or both of said inhibitor protein. WO 00/32825 PCT/IB99/02040 435
  40. 50. The method of claim 25, wherein said identifying the bacterial target comprises identifying a phage-specific site of action. 5 51. An isolated, purified, or enriched nucleic acid sequence at least 15 nucleotides in length, wherein said sequence corresponds to at least a portion of a bacteriophage sequence, and wherein said bacteriophage is selected from the group consisting of Staphylococcus aureus bacteriophage 77, 3A, 96, and 44AHJD, Enterococcus baceriophage 182, and Streptococcus pheumoniae bacteriophage Dp- 1. 10
  41. 52. The nucleic acid sequence of claim 51, wherein said sequence comprises at least 50 nucleotides.
  42. 53. The nucleic acid sequence of claim 51, wherein said nucleic acid 15 sequence corresponds to at least a portion of a nucleic acid sequence which encodes a product which provides a bacteria-inhibiting function.
  43. 54. The nucleic acid sequence of claim 53, wherein said nucleic acid sequence encodes a polypeptide which provides a bacteria-inhibiting function. 20
  44. 55. The nucleic acid sequence of claim 54, wherein said nucleic acid sequence is transcriptionally linked with regulatory sequences enabling induction of expression of said sequence. 25
  45. 56. An isolated, purified, or enriched polypeptide comprising at least a portion of a protein providing a bacteria-inhibiting function, wherein said polypeptide is normally encoded by a bacteriophage selected from the group consisting of Staphylococcus aureus bacteriophage 77, 3A, 96, and 44AHJD, Enterococcus 30 baceriophage 182, and Streptococcus pheumoniae bacteriophage Dp-1.
  46. 57. The polypeptide of claim 56, wherein said polypeptide provides said bacteria-inhibiting function. 35 58. The polypeptide of claim 56, wherein said polypeptide comprises a portion at least 10 amino acid residues in length of a said polypeptide normally encoded by said bacteriophage. WO 00/32825 PCT/IB99/02040 436
  47. 59. A recombinant vector comprising a bacteriophage ORF corresponding to an ORF from a bacteriophage having a pathogenic bacterial host, wherein said 5 bacterial host is selected from the group consisting of uncharacterized bacteria of Table 1.
  48. 60. The vector of claim 59, wherein said vector is an expression vector. 10 61. The vector of claim 59, wherein said bacteriophage is selected from the group consisting of uncharacterized bacteriophage of Table 1.
  49. 62. The vector of claim 61, wherein said bacteriophage is selected from the group consisting of Staphylococcus aureus bacteriophage 77, 3A, 96, and 44AHJD, 15 Enterococcus baceriophage 182, and Streptococcus pheumoniae bacteriophage Dp- 1.
  50. 63. The vector of claim 60, wherein expression of said ORF is inducible. 20 64. A recombinant cell comprising a vector, wherein said vector comprises an ORF from a bacteriophage having a pathogenic bacterial host, wherein said bacterial host is selected from the group consisting of bacterial species of Table 1.
  51. 65. The recombinant cell of claim 64, wherein said bacteriophage is 25 selected from the group consisting of uncharacterized phage of Table 1.
  52. 66. The cell of claim 65, wherein said bacteriophage is selected from the group consisting of Staphylococcus aureus bacteriophage 77, 3A, 96, and 44AHJD, Enterococcus baceriophage 182, and Streptococcus pheumoniae bacteriophage Dp-1. 30
  53. 67. The cell of claim 64, wherein said vector is an expresssion vector and expression of said ORF is inducible. 35 68. A method for identifying an antibacterial agent, comprising identifying an active portion of a product of a bacteria-inhibiting ORF of a bacteriophage. WO 00/32825 PCT/IB99/02040
  54. 69. The method of claim 68, further comprising constructing a synthetic peptidomimetic molecule, wherein the structure of said molecule corresponds to the structure of said active portion. 5
  55. 70. A method for identifying a compound active on a target of a bacteriophage inhibitor protein, comprising the step of contacting a bacterial target protein with a test compound; and determining whether said compound binds to or reduces the level of 10 activity of said target protein, wherein binding of said compound with said target protein or a reduction of the level of activity of said protein is indicative that said compound is active on said target and wherein said target is uncharacterized. 15 71. The method of claim 70, wherein said contacting is carried out in vitro.
  56. 72. The method of claim 70, wherein said contacting is carried out in vivo in a cell. 20 73. The method of claim 70, wherein said compound is a small molecule.
  57. 74. The method of claim 70, wherein said compound is a peptidomimetic compound. 25 75. The method of claim 70, wherein said compound is a fragment of a bacteriophage inhibitor protein.
  58. 76. The method of claim 70, further comprising determining the site of action of said compound on said target protein. 30
  59. 77. The method of claim70, wherein said contacting is performed for a plurality of said target proteins. 35 78. A method of screening for potential antibacterial agents, comprising the step of determining whether any of a plurality of compounds is active on a target of a bacteriophage inhibitor protein, WO 00/32825 PCT/IB99/02040 438 wherein said target is naturally produced by a pathogenic bacterium.
  60. 79. The method of claim 78, wherein said plurality of compounds are small molecules. 5
  61. 80. The method of claim 78, wherein said determining is performed for a plurality of said targets. 10 81. A method for inhibiting a bacterium, comprising the step of; contacting said bacterium with a compound active on a target of a bacteriophage inhibitor protein, wherein said target or the target site is uncharacterized. 15 82. The method of claim 81, wherein said compound is said protein or an active fragment thereof.
  62. 83. The method of claim 81, wherein said compound is a structural mimetic of said protein. 20
  63. 84. The method of claim 81, wherein said compound is a small molecule.
  64. 85. The method of claim 81, wherein said contacting is performed in vitro. 25 86. The method of claim 81, wherein said contacting is performed in vivo in an animal.
  65. 87. The method of claim 86, wherein said animal is a human. 30 88. The method of claim 81, wherein said contacting is carried out in vivo in a plant.
  66. 89. The method of claim 81, wherein said bacterium is selected from the group of bacteria listed in Table 1. 35 WO 00/32825 PCT/I B99/02040 439
  67. 90. A method for treating a bacterial infection in an animal suffering from an infection, comprising administering to said animal a therapeutically effective amount of compound active on a target of a bacteriophage inhibitor protein in a bacterium involved in said infection, 5 wherein said target is an uncharacterized target or the compound is active at an uncharacterized target site.
  68. 91. The method of claim 90, wherein said compound is a small molecule. 10 92. The method of claim 90, wherein said compound is a peptidomimetic compound.
  69. 93. The method of claim 90, wherein said compound is a fragment of a bacteriophage inhibitor protein. 15
  70. 94. The method of claim 90, wherein said animal is a mammal.
  71. 95. The method of claim 94, wherein said mammal is a human. 20 96. The method of claim 90, wherein said bacterium is selected from the group listed in Table 1.
  72. 97. The method of claim 90, wherein said bacteriophage inhibitor protein is from a bacteriophage selected from the group of bacteriophage listed in Table 1. 25
  73. 98. A method for propylactically treating an animal at risk of an infection, comprising administering to said animal a prophylactically effective amount of a compound active on a target of a bacteriophage inhibitor protein, 30 wherein said target is an uncharacterized target or the site of action of said compound is an uncharacterized target site.
  74. 99. The method of claim 98, wherein said compound is a small molecule. 35 100. The method of claim 98, wherein said compound is a peptidomimetic compound. WO 00/32825 PCT/IB99/02040 440
  75. 101. The method of claim 98, wherein said compound is a fragment of a bacteriophage inhibitor protein.
  76. 102. The method of claim 98, wherein said animal is a mammal. 5
  77. 103. The method of claim 102, wherein said mammal is a human.
  78. 104. An antibacterial agent active on a target of a bacteriophage inhibitor 10 protein, wherein said target is an uncharacterized target or said agent is active at a phage-specific site on said target.
  79. 105. The agent of claim 104, wherein said agent is a pepetidomimetic of a bacteriophage inhibitor polypeptide. 15
  80. 106. The agent of claim 104, wherein said agent is a small molecule.
  81. 107. The agent of claim 104, wherein said agent is a fragment of a bacteriophage inhibitor polypeptide. 20
  82. 108. The agent of claim 104, wherein said agent is active at a phage-specific site on said target. 25 109. A method of making an antibacterial agent, comprising the steps of: a) identifying a target of a bacteriophage inhibitor polypeptide; b) screening a plurality of test compounds to identify a compound active on said target; and c) synthesizing said compound in an amount sufficient to provide a 30 therapeutic effect when administered to an organism infected by a bacterium naturally producing said target.
  83. 110. The method of claim 109, wherein said compound is a small molecule. 35 111. The method of claim 109, wherein said compound is a peptidemiiimetic compound. WO 00/32825 PCT/IB99/02040 441
  84. 112. The method of claim 109, wherein said compound is a fragment or derivative of a bacteriophage inhibitor protein. 5 113. A computer readable device having recorded therein a nucleotide sequence of a portion of at least one bacteriophage genome of Staphylococcus aureus bacteriophage 77, bacteriophage 3A, or bacteriophage 96, a nucleotide sequence at least 95% identical to a said nucleotide sequence, a ribonucleic acid equivalent, a degenerate equivalent, a homologous sequence, or at least one amino acid sequence 10 encoded by said nucleotide sequence; and a nucleotide sequence or amino acid sequence analysis program, wherein said program can perform at least one sequence analysis on said nucleotide or amino acid sequence. 15 114. The device of claim 113, wherein said at least a portion of at least one bacteriophage genome comprises at least one ORF.
  85. 115. The device of claim 113, wherein said device comprises a medium selected from the group consisting of floppy disk, computer hard drive, optical disk, 20 computer random access memory, and magnetic tape wherein said nucleotide or amino acid sequence or said program or both are recorded on said medium.
  86. 116. The device of claim 113, wherein said portion of at least one bacteriophage genomic nucleotide sequence comprises at least 50% of at least one 25 bacteriophage genomic sequence.
  87. 117. The device of claim 113, wherein said at least one bacteriophage nucleotide genomic sequence comprises portions of a plurality of bacteriophage nucleotide genomic sequences. 30
  88. 118. A computer-based system for identifying biologically important portions of a bacteriophage genome, comprising: a) a data storage medium having recorded thereon a nucleotide sequence 35 corresponding to a portion of at least one bacteriophage genome, wherein said bacteriophage genome is uncharacterized; WO 00/32825 PCT/IB99/02040 442 b) a set of instructions allowing searching of said sequence to analyze said sequence; and c) an output device. 5 119. The system of claim 118, wherein said output device comprises comprises a device selected from the group consisting of a printer, a video display, and a recording medium.
  89. 120. The system of claim 118, wherein said bacteriophage genome is of a 10 bacteriophage selected from the group consisting of uncharacterized bacteriophage listed in Table 1.
  90. 121. The system of claim 118, wherein said uncharacterized bacteriophage is selected from the group consisting of bacteriophage 77, 3A, and 96. 15
  91. 122. A method for identifying or characterizing a bacteriophage ORF, comprising the steps of: a) providing a computer-based system for analyzing nucleic acid or 20 amino acid sequence data, wherein said system comprises a data storage medium having recorded thereon at least one nucleotide or amino acid sequence corresponding to a portion of at least one uncharacterized bacteriophage genome, a set of instructions allowing searching of said sequence to analyze said sequence; and an output device; b) analyzing at least a portion of at least one said sequence; and 25 c) outputting results of said analyzing to said output device.
  92. 123. The method of claim 122, wherein said analysis identifies sequence similarity or homology with sequences selected from the group consisting of bacterial ORFs encoding products with related biological function; ORFs encoding known 30 inhibitors or bacteria, essential bacterial ORFs.
  93. 124. The method of claim 122, wherein said analysis comprises identifying a probable biological function based on identification of structural elements or sequence homology or similarity. 35
  94. 125. The method of claim 122, wherein said bacteriophage is selected from the group consisting of uncharacterized bacteriophage listed in Table 1. WO 00/32825 PCT/IB99/02040 443
  95. 126. The method of claim 125, wherein said uncharacterized bacteriophage is selected from bacteriophage 77, 3A, and 96.
AU15815/00A 1998-12-03 1999-12-03 Development of novel anti-microbial agents based on bacteriophage genomics Ceased AU774841B2 (en)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US11099298P 1998-12-03 1998-12-03
US60/110992 1998-12-03
US32614499A 1999-06-03 1999-06-03
US09/326144 1999-06-03
US09/407,804 US6982153B1 (en) 1998-12-03 1999-09-28 DNA sequences from staphylococcus aureus bacteriophage 77 that encode anti-microbial polypeptides
US09/407804 1999-09-28
US15721899P 1999-09-30 1999-09-30
US60/157218 1999-09-30
US16877799P 1999-12-01 1999-12-01
US60/168777 1999-12-01
US09/454252 1999-12-02
US09/454,252 US6783930B1 (en) 1998-12-03 1999-12-02 Development of novel anti-microbial agents based on bacteriophage genomics
PCT/IB1999/002040 WO2000032825A2 (en) 1998-12-03 1999-12-03 Development of anti-microbial agents based on bacteriophage genomics

Publications (2)

Publication Number Publication Date
AU1581500A true AU1581500A (en) 2000-06-19
AU774841B2 AU774841B2 (en) 2004-07-08

Family

ID=27557794

Family Applications (1)

Application Number Title Priority Date Filing Date
AU15815/00A Ceased AU774841B2 (en) 1998-12-03 1999-12-03 Development of novel anti-microbial agents based on bacteriophage genomics

Country Status (5)

Country Link
EP (1) EP1135535A2 (en)
JP (1) JP2002531107A (en)
AU (1) AU774841B2 (en)
CA (1) CA2353563A1 (en)
WO (1) WO2000032825A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7101969B1 (en) 1998-12-03 2006-09-05 Targanta Therapeutics Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein
WO2001046383A2 (en) * 1999-12-22 2001-06-28 Phagetech, Inc. Compositions and methods involving an essential staphylococcus aureus gene and its encoded protein
JP2004522945A (en) * 2000-12-01 2004-07-29 ファゲテック,インコーポレイティド Compositions and methods related to the Staphylococcus aureus essential gene and its encoded protein STAAU_R2
US7326541B2 (en) 2000-12-19 2008-02-05 Targanta Therapeutics, Inc. Fragments and variants of Staphylococcus aureus DNAG primase, and uses thereof
AU2002224692B2 (en) * 2000-12-20 2007-05-24 Targanta Therapeutics Inc. Compositions and methods involving an essential staphylococcus aureus gene and its encoded protein STAAU_R4
WO2003024410A2 (en) * 2001-09-21 2003-03-27 New Horizons Diagnostics Corporation Composition for treating streptococcus pneumoniae
US6759229B2 (en) 2001-12-18 2004-07-06 President & Fellows Of Harvard College Toxin-phage bacteriocide antibiotic and uses thereof
ATE498010T1 (en) * 2004-03-01 2011-02-15 Immune Disease Inst Inc NATURAL IGM ANTIBODIES AND INHIBITORS THEREOF
US7569223B2 (en) 2004-03-22 2009-08-04 The Rockefeller University Phage-associated lytic enzymes for treatment of Streptococcus pneumoniae and related conditions
GB201119167D0 (en) * 2011-11-07 2011-12-21 Novolytics Ltd Novel bachteriophages
JP6162319B2 (en) 2013-03-12 2017-07-12 デシミューン セラピューティクス,インコーポレイテッド Humanized anti-N2 antibody
CN111316999B (en) * 2020-03-04 2022-02-08 苏州十一方生物科技有限公司 Spray type environmental disinfectant containing bacteriophage and preparation method and application thereof
CN111296493A (en) * 2020-03-09 2020-06-19 苏州十一方生物科技有限公司 Phage disinfectant and preparation method thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1207253A (en) * 1981-08-17 1986-07-08 Lee D. Simon T4 dna fragment as a stabilizer for proteins expressed by cloned dna
CA1327311C (en) * 1987-07-06 1994-03-01 Jesse M. Jaynes Therapeutic antimicrobial polypeptides, their use and methods for preparation
WO1995027043A1 (en) * 1994-04-05 1995-10-12 Exponential Biotherapies, Inc. Antibacterial therapy with genotypically modified bacteriophage
ATE247711T1 (en) * 1995-06-16 2003-09-15 Nestle Sa PHAGE RESISTANT STREPTOCOCCUS

Also Published As

Publication number Publication date
WO2000032825A3 (en) 2001-01-18
EP1135535A2 (en) 2001-09-26
CA2353563A1 (en) 2000-06-08
WO2000032825A2 (en) 2000-06-08
AU774841B2 (en) 2004-07-08
JP2002531107A (en) 2002-09-24

Similar Documents

Publication Publication Date Title
US6783930B1 (en) Development of novel anti-microbial agents based on bacteriophage genomics
AU774841B2 (en) Development of novel anti-microbial agents based on bacteriophage genomics
US6638718B1 (en) Methods of screening for compounds active on staphylococcus aureus target genes
KR102003770B1 (en) Novel Staphylococcus specific bacteriophage SA3 and antibacterial composition comprising the same
KR101592177B1 (en) Method for prevention and treatment of Escherichia coli infection using a bacteriophage with broad antibacterial spectrum against Escherichia coli
CN109082414B (en) Staphylococcus aureus bacteriophage and application thereof
CN107208068B (en) Novel Shiga toxin F18-producing Escherichia coli bacteriophage Esc-COP-1 and application thereof in inhibiting proliferation of Shiga toxin F18-producing Escherichia coli
CN108359643A (en) Novel staphylococcus aureus bacteriophage and combinations thereof and application
KR102073095B1 (en) Escherichia coli bacteriophage Esc-COP-14 and its use for preventing proliferation of pathogenic Escherichia coli
CN107208067A (en) New enteroinvasive E.Coli phage E sc COP 4 and its purposes for suppressing enteroinvasive E.Coli propagation
KR102432624B1 (en) Novel Staphylococcus specific bacteriophage OPT-SC01 and antibacterial composition comprising the same
KR20210143684A (en) Endolysins LysPALS21 of Jumbo bacteriophage PALS2 from Staphylococcus aureus
KR101993123B1 (en) Novel pathogenic Escherichia coli specific bacteriophage ECO5 and antibacterial composition comprising the same
US6376652B1 (en) Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein
AU778782B2 (en) Compositions and methods involving an essential staphylococcus aureus gene and its encoded protein
KR102418861B1 (en) Bacteriophage with growth inhibition activity against Staphylococcus sp.
KR102203675B1 (en) Novel Yersinia specific bacteriophage YE12 and antibacterial composition comprising the same
US20030138771A1 (en) DNA sequences from S. pneumoniae bacteriophage DP1 that encode anti-microbal polypeptides
KR102334893B1 (en) Novel Campylobacter specific bacteriophage OPT-CJ1 and antibacterial composition comprising the same
KR101992013B1 (en) Novel bacteriophage having bacteriocidal activity against pathogenic enterobacteria and uses thereof
US20070059709A1 (en) Staphylococcus aureus antibacterial target genes
KR102275107B1 (en) Novel bacteriophage specific for Acinetobacter genus bacteria resistant to antibiotics
KR20230112860A (en) Staphylococcus specific bacteriophage KMSP1 and antibacterial composition comprising the same
KR102066898B1 (en) Novel Enterococcus faecalis specific bacteriophage EF5 and antibacterial composition comprising the same
KR101993125B1 (en) Novel ESBL producing Escherichia coli specific bacteriophage ECO4 and antibacterial composition comprising the same

Legal Events

Date Code Title Description
MK6 Application lapsed section 142(2)(f)/reg. 8.3(3) - pct applic. not entering national phase
MK6 Application lapsed section 142(2)(f)/reg. 8.3(3) - pct applic. not entering national phase
TH Corrigenda

Free format text: IN VOL 14, NO 37, PAGE(S) 6637-6641 UNDER THE HEADING APPLICATIONS LAPSED, REFUSED OR WITHDRAWN PLEASE DELETE ALL REFERENCE TO APPLICATION NO. 15815/00

FGA Letters patent sealed or granted (standard patent)