AU2003236302B2 - Virulence genes and proteins, and their use - Google Patents

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Regulation 3.2

AUSTRALIA

Patents Act 1990 COMPLETE

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Invention Title: Microscience Limited Virulence Genes and Proteins, and their use.

The following statement is a full description of this invention, including the best method of performing it known to me: CommonWordV7\I 3001-13500\131 74mrc\20030819.doc VIRULENCE GENES AND PROTEINS, AND THEIR USE Field of the Invention This invention relates to the identification of virulence genes and proteins, and their use. More particularly, it relates to their use in therapy and in screening for drugs.

Backaround to the Invention E. coli is a member of the Enterobacteriaceae, or enteric bacteria, which are Gram-negative microorganisms that populate the intestinal tracts of animals. Other members of this bacterial family include Enterobacter, Klebsiella, Salmonella, Shigella and Yersinia. Although E. coi is found normally in the human gastrointestinal tract, it has been implicated in human disease, including septicaemia, meningitis, urinary tract infection, wound infection, abscess formation, peritonitis and cholangitis.

The disease states caused by E. coi are dependent upon certain virulence determinants. For example, E. coli has been implicated in neonatal meningitis and a major determinant of virulence has been identified as the K1 antigen, which is a homopolymer of sialic acid. The K1 antigen may have a role in avoiding the host's immunological system and preventing phagocytosis.

Summary of the Invention The present invention is based on the identification of a series of virulence genes in E. coil K1, and also related organisms the products of which may be implicated in the pathogenicity of the organism.

According to one aspect of the present invention, a peptide is encoded by an operon including any of the genes identified herein as mdoG, creC, recG, yggN, tatA, tatB, tatC, tatE, eckl, iroD, iroC, iroE, mtd2 and ms1 to 16, from E.

coli K1, or a homologue thereof in a Gram-negative bacterium, or a functional fragment thereof. Such a peptide is suitable for therapeutic use, e.g. when isolated.

The term "functional fragments" is used herein to define a part of the gene or peptide which retains similar therapeutic utility as the whole gene or peptide. For example, a functional fragment of the peptide may be used as an antigenic determinant, useful in a vaccine or in the production of antibodies.

2 A gene fragment may be used to encode the active peptide. Alternatively, the gene fragment may have utility in gene therapy, targetting the wild-type gene in vivo to exert a therapeutic effect A peptide according to the present invention may comprise any of the amino acid sequences identified herein as SEQ ID NOS. 2, 5, 7, 9, 11, 12, 13, 14, 16, 23, 24, 25, 26, 28, 31, 29, 32 and 35-48.

The identification of these peptides as virulence determinants allows them to be used in a number of ways in the treatment of infection. For example, a host may be transformed to express a peptide according to the invention or modified to disrupt expression of the gene encoding the peptide. A vaccine may also comprise a peptide according to the invention, or the means for its expression, for the treatment of infection. In addition, a vaccine may comprise a microorganism having a virulence gene deletion, wherein the gene encodes a peptide according to the invention.

According to another aspect of the invention, the peptides or genes may be used for screening potential antimicrobial drugs or for the detection of virulence.

A further aspect of this invention is the use of any of the products identified herein, for the treatment or prevention of a condition associated with infection by a Gram-negative bacterium, in particular by E coli.

Description of the Invention The present invention has made use of signature-tagged mutagenesis (STM) (Hensel et al, Science, 1995;269:400-403) to screen E. coli K1 strain RS228 (Pluschke et al, Infection and Immunity 39:599-608) mini-Tn5 mutant bank for attenuated mutants, to identify virulence genes (and virulence determinants) of E. coli.

Although E. coli K1 was used as the microorganism to identify the virulence genes, corresponding genes in other enteric bacteria are considered to be within the scope of the present invention. For example, corresponding genes or encoded proteins may be found, based on sequence homology, in Enterobacter, Klebsiella and other genera implicated in human intestinal disease, including Salmonella, Shigella and Yersinia.

The term "virulence determinant" is used herein to define a product, e.g.

a peptide or protein that may have a role in the maintenance of pathogenic bacteria. In particular, a virulence determinant is a bacterial protein or peptide that is implicated in the pathogenicity of the infectious or disease-causing microorganism.

A gene that encodes a virulence determinant may be termed a "virulence gene". Disruption of a virulence gene by way of mutation, deletion or insertion will result in a reduced level of survival of the bacteria in a host, or a general reduction in the pathogenicity of the microorganism.

Signature-tagged mutagenesis'has proved a very useful technique for identifying virulence genes, and their products. The technique relies on the ability of transposons to insert randomly into the genome of a microorganism, under permissive conditions. The transposons are individually marked for easy identification, and then introduced separately into a microorganism, resulting in disruption of the genome. Mutated microorganisms with reduced virulence are then detected by negative selection and the genes where insertional inactivation has occurred are identified and characterised.

A first stage in the STM process is the preparation of suitable transposons or transposon-like elements. A library of different transposons are prepared, each being incorporated into a vector or plasmid to facilitate transfer into the microorganism. The preparation of vectors with suitable transposons will be apparent to a skilled person in the art and is further disclosed in WO-A- 96/17951. For the Gram-negative bacteria, e.g. E. coli, suitable transposons include Tn5 and Tnl0. Having prepared the transposons, mutagenesis of a bacterial strain is then carried out to create a library of individually mutated bacteria.

Pools of the mutated microorganisms are then introduced into a suitable host. After a suitable length of time, the microorganisms are recovered from the host and those microorganisms that have survived in the host are identified, thereby also identifying the mutated strains that failed to survive, i.e. avirulent strains. Corresponding avirulent strains in a stored library are then used to identify the genes where insertional inactivation occurred. Usually, the site of transposon insertion is identified by isolating the DNA flanking the transposons insertion site, and this permits characterisation of the genes implicated in virulence.

Once an avirulent microorganism has been identified, it is possible to 5 determine more fully the potential role of the mutated gene in virulence, by infecting a suitable host animal with a lethal dose of the mutant. The survival time of the infected animal is compared with that of a control infected with the wild-type strain, and those animals surviving for longer periods than the control may be said to be infected with microorganisms having mutated virulence genes.

Alternatively, the potential role in virulence can be investigated by infecting an animal host with a mixture of the wild-type and mutant bacteria.

After a suitable period of time, bacteria are harvested from organs of the host animal and the ratio of wild-type and mutant bacteria determined. This ratio is divided by the ratio of mutant to wild-type bacteria in the inoculum, to determine the competitive index Mutants which have a competitive index of less than 1 may be said to be avirulent.

It is possible that the gene which is inactivated by the insertion of the transposon may not be a true virulence gene, but may be having a polar effect on a downstream (virulence) gene. This can be determined by further experimentation, placing non-polar mutations in more defined regions of the gene, or mutating other adjacent genes, and establishing whether or not the mutant is avirulent.

Having characterised a virulence gene in E. coil, it is possible to use the gene sequence to establish homologies in other microorganisms. In this way it is possible to determine whether other microorganisms have similar virulence determinants. Sequence homologies may be established by searching in existing databases, e.g. EMBL or Genbank Virulence genes are often clustered together in distinct chromosomal regions called pathogenicity islands. Pathogenicity islands can be recognised as they are usually flanked by repeat sequences, insertion elements or tRNA genes. Also the G+C content is normally different from the remainder of the chromosome, suggesting that they were acquired by horizontal transmission from another organism. For example the G+C content of the E. coli K12 genome is 52%. Any pathogenicity islands found in E. coli strains are likely to have a G+C content that varies from this average.

The identified virulence genes are likely to be useful both in generating attenuated vaccine strains and as a target for antimicrobials. The same may be true for homologues in Gram-negative bacteria in general.

For the purpose of this invention, the appropriate degree of homology is typically at least 30%, preferably at least 50%, 60% or 70%, and more preferably at least 80% or 90% (at the amino acid or nucleotide level).

Proteins according to the invention may be purified and isolated by methods known in the art. In particular, having identified the gene sequence, it will be possible to use recombinant techniques to express the genes in a suitable host. Active fragments and homologues can be identified and may be useful in therapy. For example, the proteins or their active fragments may be used as antigenic determinants in a vaccine, to elicit an immune response.

They may also be used in the preparation of antibodies, for passive immunisation, or diagnostic applications. Suitable antibodies include monoclonal antibodies, or fragments thereof, including single chain fv fragments. Methods for the preparation of antibodies will be apparent to those skilled in the art.

The preparation of vaccines based on attenuated microorganisms is known to those skilled in the art. Vaccine compositions can be formulated with suitable carriers or adjuvants, e.g. alum, as necessary or desired, and used in therapy, to provide effective immunisation against E. co/i or other Gramnegative bacteria. The preparation of vaccine formulations will be apparent to the skilled person.

More generally, and as is well known to those skilled in the art, a suitable amount of an active component of the invention can be selected, for therapeutic use, as can suitable carriers or excipients, and routes of administration. These factors will be chosen or determined according to known criteria such as the nature/severity of the condition to be treated, the type or health of the subject etc.

The following Examples illustrate the invention. For the Examples,

STM

was used to screen an E. coli K1 mini-Tn5 mutant bank for attenuated mutants using a mouse model of systemic infection. The basic procedure followed that disclosed in Hensel et supra. E coli K1 containing a mini-Tn5 insertion within a virulence gene was not recovered from mice inoculated with a mixed population of mutants, and is therefore likely to be attenuated.

The DNA region flanking either side of the mini-Tn5 insertion was cloned by inverse PCR or by rescue of a kanamycin-resistance marker. In the latter case, chromosomal DNA from the STM-derived mutant was digested with restriction enzymes, ligated into the plasmid pUC19, and kanamycin-resistant clones selected after transformation into competent E. coil K12 cells.

Subsequent cloning and sequencing was then performed and the gene sequences compared using sequences in publicly available sequence databases (EMBL) to help characterise the putative gene products.

Example 1 In a first mutant, two fragments of cloned DNA were sequenced. The nucleotide sequences are shown as SEQ ID NO. 1 and SEQ ID NO. 3 and a translated region of the DNA from SEQ ID NO. 1 is shown as SEQ ID NO. 2.

SEQ ID NO. 1 shows 99.8% identity to the mdoGH region from E co/i K12 (EMBL database accession number AE000206) from nucleotides 2577 to 6908.

This DNA fragment encodes the 5'-part of the ymdD gene, the entire mdoG gene and the 5'-part of the mdoH gene. The product of the mdoG gene is of unknown function, but is believed to be involved in the biosynthesis of membrane-derived oligosaccharides.

SEQ ID NO. 3 shows 98.3% identity to the 3'-part of the mdoH gene and downstream gene sequences from E. co/i K12 (nucleotides 7187 to 7760).

SEQ

ID NO. 2 shows 99.6% identity to the mdoG protein from E. coliK12 (Swiss Prot accession number P33136) at amino acid 1 to 511.

The novel gene was tested for attenuation of virulence, using mixed infections, in a murine model of systemic infection (Achtman et al, Infection and Immunity, 1983; Vol. 39:315-335), and shown to be attenuated with a competitive index (Cl) of 0.38. This confirms that the attenuation of the original transposon mutant is likely to be due to the disruption of the mdoG gene.

Polar and a non-polar deletion mutants of mdoG were constructed. The mdoG gene and flanking regions were amplified by PCR with oligonucleotides 5'-TGCTCTAGAGCCATTACTCAGAATGGG-3- (SEQ ID NO. 49) and CGCGAGCTCGACGACTGAATGATCCC-3 (SEQ ID NO. 50). The product was cloned into pUC19. A PCR product containing and 3 '-terminal fragments of mdoG and the entire pUC19 sequence was then amplified by inverse PCR with the oligonucleotides 5'-TCCCCGGGTACTGCAGCACTCAACC-3' (SEQ ID NO. 51) and 5'-GATCCCGGGACCACTGAAATGCGTGC-3' (SEQ ID NO. 52).

A non-polar kanamycin resistance cassette (aphT) was inserted in both orientations between the mdoG sequences to give a polar and a non-polar construct. The mdoG::aphTfusions were then transferred to the suicide vector pCDV442. The chromosomal copy of the mdoG was mutated by allefic transfer after conjugation of the pCDV442 constructs into wild type E. coi K1.

The contructed mutants were tested for attenuation of virulence in a murine model of systemic infection (Achtman et al., supra). Both the polar and the non-polar constructs were attenuated in virulence, with competitive indices of 0.37 and 0.35, respectively (mean Cl from three mice each). This confirms that the attenuation of the original transposon mutant is likely to be due to the disruption of the mdoG gene.

Example 2 A second mutant was identified with a virulence gene having the nucleotide sequence shown in SEQ ID NO. 4 and the translated amino acid sequence shown as SEQ ID NO. 5. The mini-Tn5 transposon inserted at nucleotide 581 (SEQ ID NO. 4) and at amino acid 187 (SEQ ID NO. These sequences show 97.9% identity to the creC gene of E. coli K12 (EMBL and Genbank accession numbers M13608, AE000510 and U14003).

The creC protein from E. coli K12 belongs to the protein family of histidine kinases as well as to a protein family consisting of proteins containing a signal domain.

The novel gene was tested for attenuation of virulence (Achtman et al, supra.), and shown to be attenuated with a competitive index of 0.09.

As the E. coliK12 creC gene is transcribed as part of an operon with the creD gene, it is possible that this attenuation is due to a polar effect on a presumed E. coil K1 creD gene.

Example 3 A third mutant had a nucleotide sequence shown as SEQ ID NO. 6 immediately following the mini-Tn5. A translation of this sequence is shown as SEQ ID NO. 7.

The nucleotide sequence shows 93.7% identity to the recG gene of E co/i K12, at nucleotides 5-146 (EMBL and Genbank accession numbers P24230 and M64367). This demonstrates that the disrupted gene is at least partially identical to the recG gene of E. coli K12. The recG gene of E. coli K12 encodes a 76.4kD protein which functions as ATP-dependent DNA helicase, and plays a critical role in DNA repair.

In tests for attenuation, the competitive index was shown to be 0.48. The recG gene is transcribed as the terminal gene of an operon, and it is therefore unlikely that this attenuation is due to a polar effect on another E. coli K1 gene.

Example 4 A fourth mutant had a transposon inserted within the nucleotide sequence shown as SEQ ID NO. 8, with a translation product shown as SEQ ID NO. 9.

The mini-Tn5 transposon inserted at nucleotide 359 and amino acid These sequences show 98.5% sequence identity to the yggN gene of E co/i K12 (EMBL accession number AE000378) at nucleotides 339-1054, and 99.6% identity at the amino acid level.

Although the sequence of the yggN gene is known, the function of its encoded protein has not yet been determined.

The novel gene was tested for attenuation of virulence, and shown to be 3 o attenuated with a competitive index of 0.43.

Example Several mutants were also found with a transposon insertion within the same region. Cloning and sequencing the region revealed a nucleotide sequence shown as SEQ ID NO. 10. This sequence has homology with the tatABCD operon of E. coli K12 (EMBL and Genbank accession numbers AJ005830, AE000459 and AE000167). This operon encodes proteins of predicted mass 9.6 kD, 18.4 kD, 28.9 kD and 29.5 kD, which function as components of a Sec-independent protein export pathway. The pathway permits translocation of fully folded proteins to the periplasm through a gated pore, after the attachment of co-factors in the cytoplasm.

Translation of the nucleotide sequence revealed a protein corresponding to tatA (SEQ ID NO. 11), a sequence corresponding to tatB (SEQ ID NO. 12), a sequence corresponding to tatC (SEQ ID NO. 13) and a sequence corresponding to tatD (SEQ ID NO. 14).

The mini-Tn5 transposons in the mutants identified by STM are located at nucleotides 1429 and 2226 of SEQ ID NO. 10. These transposon insertions disrupt the tatB protein sequence at amino acid 50 and the tatC protein sequence at amino acid 143.

The tatB and tatC genes were tested for attenuation of virulence and were shown to be attenuated with competitive indices of 0.0012 and 0.0039, respectively. These genes were also attenuated in virulence when tested in single infections in the same model of systemic infection.

Example 6 A further mutant was insertionally inactivated within a region corresponding to the tatE gene of E. co/i K12, shown as SEQ ID NO. 15. A translation of the sequence as shown as SEQ ID NO. 16. The tatE gene shows 98% identity to that of the E. coli K12 gene (accession number AE000167) at nucleotides 6719-7306.

To establish whether the tatA, tatD and tatE genes are required for virulence, non-polar deletion mutations were constructed in each. The regions 3o of DNA flanking either side of the tatA, tatD and tatE genes were amplified with the following primers: tatA TCT AGA GAT GAT GGT GAT GGA GCG-3' (SEQ ID NO. 53) 5'-GAA CTG CAG CCA AAT ACT GAT ACC ACC C-3' (SEQ ID NO. 54) CTG CAG GCT AAA ACA GAA GAC GCG-3' (SEQ ID NO. lo 5'-CAT GCA TGC ACT CCA TAT GAC AAC CGC-3' (SEQ ID NO. 56) Primers SEQ ID NO. 53 and SEQ ID NO. 54 were used to amplify

DNA

sequences upstream oftatA, Primers SEQ ID NO. 55 and SEQ ID NO. 56 were used to amplify DNA sequences downstream of tatA.

tatD TCT AGA ATG AAG CTG CGC ATG AGG-3' (SEQ ID NO. 57) 5'-CAA CTG CAG TCG CAA ATT GCG AAC TGG-3' (SEQ ID NO. 58) CTG CAG ACC GCA ACT TTT CGA CGC-3' (SEQ ID NO. 59) GCA TGC CAG TGA GCC ATT GTT CCC-3' (SEQ ID NO. Primers SEQ ID NO. 57 and SEQ ID NO. 58 were used to amplify

DNA

sequences upstream of tatD, Primers SEQ ID NO. 59 and SEQ ID NO. 60 were used to amplify DNA sequences downstream of tatD.

tatE TCT AGA TAC GAC TCT GAC AGG AGG-3' (SEQ ID NO. 61) GAT ATC AAC TAC CAG CAG TTT GG-3' (SEQ ID NO. 62) 5'-TCA GAT ATC CAT AAA GAG TGA CGT GGC-3' (SEQ ID NO. 63) TCT AGA AAA CGT GGC AAC AGA GCG-3' (SEQ ID NO. 64) Primers SEQ ID NO. 61 and SEQ ID NO. 62 were used to amplify

DNA

sequences upstream of tatE, Primers SEQ ID NO. 63 and SEQ ID NO. 64 were used to amplify DNA sequences downstream of tatE.

After cloning these flanking DNA fragments into pUC19, a non-polar aph T kanamycin resistance cassette (Galan etal, J.Bacteriol, 1992; 174:4338- 4349) was inserted between the flanking DNA fragments to replace the tatA, tatD and tatE genes. These DNA fragments were then transferred to the suicide vector pCVD442 (Blomfield et. al, Mol. Micro., 1991;5:1447-1457). The chromosomal copies of the E. coli K1 tatA, tatD and tatE genes were then mutated by allelic transfer after conjugation of the pCVD442 constructs into wild type E. coli K1.

Disruptions of the tatA, tatD and tatE genes have been tested for attenuation of virulence (Achtman et al., supra).

None of the genes was attenuated when deleted in isolation. The genes may still play a role in virulence, and to test this, mutants were prepared with deletions in both tatA and tatE genes. The double mutant was tested for attenuation in virulence using mixed infections with the wild-type strain and shown to be attenuated with a competitive index of 0.0017. It seems therefore that the tatA, tatD and tatE genes may be used in combination to create avirulent microorganisms.

Given the similarity of the E. coli K1 tatABCD genes to predicted tatABCD genes present in the S. typhimuiuum genome and Neisseria meningitidis genome it seemed likely that the tat system may also be required for virulence in these, and other, organisms. A deletion in the S. typhimurium tatC gene (SEQ ID NO. 17) was constructed by amplifying the DNA flanking either side of the tatC gene with the following primers: 5'-TGC TCT AGA AGG CGT TGT CGA TCC TG-3' (SEQ ID NO. CTG CAG GAA AAG GCC GAG CAG ACT G-3' (SEQ ID NO. 66) CTG CAG TAC AGC CAT GTT TAC GGT-3' (SEQ ID NO. 67) GCA TGC GGT GTA CGA CAG TTT GCG-3' (SEQ ID NO. 68) Primers SEQ ID NO. 65 and SEQ ID NO. 66 were used to amplify

DNA

sequences downstream of the S. typhimurium tatC gene, Primers SEQ ID NO.

67 and SEQ ID NO. 68 were used to amplify DNA sequences upstream of the S. typhimurium tatC gene.

The encoded amino acid sequences for two regions of the tatC gene are shown as SEQ ID NO. 18 and SEQ ID NO. 19.

After cloning these flanking DNA fragments into pUC19, a non-polar kanamycin resistance cassette (aphT) was inserted between the flanking

DNA

fragments to replace the S. typhimurium tatC gene. This DNA fragment was o1 then transferred to the suicide vector pCVD442. The chromosomal copy of the S. typhimurium tatC gene was then mutated by allelic transfer after conjugation of the pCVD442 construct into wild type S. typhimurium strains TML and SL1344.

The disrupted S. typhimurium tatC gene was tested for attenuation of virulence, using mixed and single infections in a murine model of systemic infection. For mixed infections, 6-7 week old balbC mice were inoculated intraperitoneally with 104 bacterial cells. Competitive indices were calculated after comparing the numbers of mutant and wild-type bacteria present in spleens after 3 days. For single infections, mice were inoculated either intraperitoneally or orally with varying doses and mouse survival monitored for 17 days. The strains were attenuated in virulence, the competitive indices of the SL1344 tatC and TML tatC deletion strains being 0.078 and 0.098, respectively.

In single infections, mouse survival was extended compared to the wildtype controls.

Sequence homology was also demonstrated with the tat sequence from Neisseria meningitidis. The gene sequence from N. meningitidis is shown as SEQ ID NO. 20 and the encoded amino acid sequence for tatC is shown as SEQ ID NO. 21.

To test for virulence, a deletion mutant was created using the following primers: 13 5'-TGCTCTAGACACATCATGGGCACACC-3' (SEQ ID NO. 69) 5'-GAACTGCAGAACCGTCCACATCAGGCG-3' (SEQ ID NO. 5'-GAACTGCAGACCCTGCTTGCCATTCCG-3' (SEQ ID NO. 71) 5'-GAACTGCAGACCCTGCTTGCCATTCCG-3' (SEQ ID NO. 72) Cloning of the DNA fragments and the aphT kanamycin resistance cassette into pUC19 followed the procedure outlined above for S. typhimurium.

The chromosomal copy of the N. meningitidis tatC gene was mutated by transformation of the pUC19-based constructs into wildtype N. meningitidis cells.

Southern analysis of the resulting transformants indicated that all the transformants were merodiploids and contained both the wild-type and mutated copies of the tatC gene. This indicates that there is some selection against the isolation of mutants in which the tatC gene has been deleted.

Further studies on polar and non-polar constructs showed that transformants did not grow on selective media. This suggests that the N.

meningitidis tatC gene is essential for the in vitro growth of this organism.

Example 7 A further mutant was identified with a transposon insertion within a nucleotide sequence identified herein as SEQ ID NO. 22, at nucleotide 3981.

The sequence defined herein as eckI, shows sequence homology to several Group 1 glycosyltransferases from a number of bacteria. Sequence homology was also shown to the gnd gene of E. coli K12 (at nucleotides 4197-4604 of SEQ ID NO. 22).

The translation of the E. coli eckI gene is shown as SEQ ID NO. 26.

The gene has been tested for attenuation of virulence, as described above, and 3 o is shown to be attenuated with a competitive index of 0.025.

Several open reading frames (ORF) were also identified from the DNA sequence (SEQ ID NO. 22). The first of these is defined herein as MS1 and a translation product shown as SEQ ID NO. 25. The amino acid sequence is shown to have 50.3% identity to a putative glycosyl transferase from E. coil serotype 0111 (TrEMBL database accession number AAD46732). The amino acid sequence also shows homology with the eckl protein from E. coli K1 and also the TrsE protein from Yersinia entercolitica (TrEMBL database accession number Q56917).

A second open reading frame identified herein as MS2 had the gene sequence shown as SEQ ID NO. 24. This shows sequence homology to the putative glycosyl transferase TrsC from Yersinia entercolitica (TrRMBL database accession number Q56915), and also the glycosyl transferase WbnA from E. coli serotype 0113 (TrEMBL database accession number AAD50485).

A third open reading frame encodes a product identified herein as MS3 (SEQ ID NO. 23). The amino acid sequence shows 30.2% identity to a rhamnosyltransferase from Streptoccus mutans.

The gene sequence shown as SEQ ID NO. 22 may be at least part of a pathogenicity island, with multiple virulence genes being positioned in a cluster on the microorganism's genome.

Example 8 A further mutant was identified having a transposon insertion within the iroCDE operon. The nucleotide sequences flanking either side of the insertion are shown as SEQ ID NO. 27 and SEQ ID NO. The mini-Tn5 transposon is inserted at nucleotide 1272 of SEQ ID NO.

27 and at nucleotide 1 of SEQ ID NO. 30, and interrupts the iroD gene. The Nterminal region of iroD is shown as SEQ ID NO. 29, and the C-terminal region is shown as SEQ ID NO. 31.

In addition to iroD, the gene shown as SEQ ID NO. 27 encodes a partial peptide with the amino acid sequence shown as SEQ ID NO. 28. This amino acid sequence shows 70.9% identity to the putative ATP binding cassette transporter iroC from Salmonella typhi.

The gene sequence shown as SEQ ID NO. 30 includes an open reading frame that encodes a peptide with the amino acid sequence shown as SEQ ID NO. 32 and this has sequence homology to the iroE protein from Salmonella typhi.

Testing the genes in a model for attenuation of virulence, as described above, showed that the iroD gene was attenuated with a competitive index of 0.107. The mini-Tn5 mutation in the iroD gene has been reintroduced into the wild-type E. coliK1 strain by P1 transduction. The resulting transductant is also attenuated in virulence with a competitive index of 0.1. This indicates that the attenuated phenotype is linked to the insertion within iroD. However, it is possible that the attenuation is due to a polar effect on the E. coli K1 iroE gene.

Example 9 A further mutant was identified with a transposon insertion within the nucleotide sequence shown as SEQ ID NO. 33. The transposon is inserted at nucleotide 2264 of SEQ ID NO. 33. The nucleotide sequence shows sequence homology to the asIA hemY region of E. coli K12 (EMBL accession number AE000456). The asIA encodes an arylsulfatase homologue whereas hemYis involved in the biosynthesis of protoheme IX. This demonstrates that the disrupted region is at least partially identical to the asIA /hem Y region of E. co/ K12.

The transposon is inserted at nucleotide 2264 of SEQ ID NO. 33. This insertion site is 216 nucleotides downstream from the stop codon of the hemY gene and 472 nucleotides upstream from the start codon of the as/A gene.

The novel region has been tested for attenuation of virulence, as described above, and shown to be attenuated with a competitive index of 0.033.

The mini-Tn5 mutation in this region has been reintroduced into the wild-type E. coli K1 strain by P1 transduction. The resulting transductant is also attenuated in virulence with a competitive index of 0.008. This indicates that the attenuated phenotype is linked to the transposon insertion in this region.

However, polar and non-polar deletion mutants of asIA were constructed and tested for attenuation of virulence as described above.

Neither the polar nor the non-polar mutants were attenuated in virulence and this demonstrates that the attenuation of the original transposon mutant is 3 o not due to a polar effect on the as/A gene. This indicates that the transposon is disrupting some other function encoded within the intergenic region between as/A and hemY. For example there could be some untranslated RNA molecule, such as a regulatory RNA similar to oxyS (Altuvia et al., Cell, 1997;90:43-53), encoded within this region. Alternatively the transposon could be disrupting some DNA structure that may, for example, be involved in DNA replication.

This DNA region is also present in the pathogen Salmonella typhimurium suggesting that it may be important for pathogenicity in other organisms. This region (SEQ ID NO. 33) may be used as a target, to identify anti-microbial drugs.

Example A further mutant was identified and the DNA region flanking either side of the mini-Tn5 insertion was cloned and had the nucleotide sequence shown as SEQ ID NO. 34. This nucleotide sequence has homology with the mtd2 gene of Herpetosiphon aurantiacus (EMBL accession number P25265), with the mtd2 gene product functioning as a cytosine-specific methyltransferase. The mtd2 gene is not found in the E. coil K12 genome and may represent a pathogenicity island.

The mini-Tn5 transposon insertions were located at nucleotides 4773 and 3764 of SEQ ID NO. 34 and were shown to interrupt the mtd2 gene.

The amino acid sequence of the mtd2 gene is shown as SEQ ID NO. 43.

The E. co/i K1 mtd2 gene was tested for attenuation of virulence, as 2 0 described above, and shown to be attenuated with a competitive index of 0.073.

In addition to the mtd2 gene, a series of open reading frames were also identified with translation products identified herein as MS4 to MS16, SEQ ID NOS. 48-44 and 42-35, respectively. As the open reading frames are located in a potential pathogenicity island, mutations in these genes may also result in attenuation in virulence. Further, since it is known that E. coli and other bacteria may encode peptides in different forms in the nucleotide sequence, the coding regions of some of these proteins may overlap. In addition, any aminoacid sequence shown starting with Val may in fact start with Met

Claims (13)

1. An isolated peptide encoded by the gene identified herein as mdoG, obtainable from E. col K1, or a homologue thereof in a Gram-negative bacterium, having at least homology at the amino acid or nucleotide level, or a functional fragment thereof, when used in therapy.

2. A peptide according to claim 1, comprising the amino acid sequence identified herein as SEQ ID NO 2.

3. A polynucleotide encoding a peptide according to claim 1 or claim 2, when used in therapy.

4. A host transformed to express a peptide according to claim 1 or claim 2. A vaccine comprising a peptide according to claim 1 or claim 2, or the means for its expression.

6. A vaccine comprising a microorganism having a mutation that disrupts the expression of the gene that encodes a peptide according to claim 1 or claim 2.

7. A vaccine according to claim 6, wherein the microorganism has a second mutation that disrupts a different gene.

8. A vaccine according to claim 7, wherein the second mutation is in a gene within a pathogenicity island, wherein the island comprises a gene identified herein.

9. A method for screening a potential antimicrobial drug, said method comprising contacting a mdoG peptide, obtainable from E. col or a homologue thereof in a Gram- negative bacterium, having at least 30% homology at the amino acid level, or a functional fragment thereof, with the potential drug, and determining activity of the peptide. Use of a product according to any of claims 1 to 4, for the manufacture of a medicament for use in the treatment or prevention of a condition associated with infection by a Gram-negative bacterium.

11. Use according to claim 10, wherein the bacterium is E. coil. 18 Marked Up Copy s0 O 10. Use of a product according to any of claims 1 to 4, for the manufacture of a medicament for use in the treatment or prevention of a condition associated with infection by a Gram-negative bacterium. 11. Use according to claim 10, wherein the bacterium is E. coli. <110> Micz <120> VIRU <130> REPO <140> <141> <160> 72 <170> Pate <210> 1 <211> 4333 <212> DN.A <213> Esch <22 0> <22 1> CDS <222> (101 <400> 1 ccattactca. atgccgaggc tcagaatttt accactaaca ttgtcataca ataaattgcg acacgtacti ccggatataa agccataatg atatgaaaag cgttgcgcgg SEQUENCE LISTING oscience Limited 'LENCE GENES AND PROTEINS, AND THEIR USE 5921iWO ntln Ver. 2.1 erichia coli 7) (2549) gaatgggcgg acaaaaaaat ctaaattatt ccagtaaaaa atgacagtcc gcaatgtcag tccaccattt cgaaaaatac acggttcggc ggatccctaa gtactgggtt atacacaata caccgatagt tctgatacgt ccacaggtgt aggccaactt tagggggatg tttcaaggga ctgcatgcgg gctattcaca caacatcagc catatatggt aaaattgttc tttaccatcg ttgaatatcc gatattaati tccgctttcc gcigttaaca tagcgtaaaa aacgagtgga tgccatgtat caggcgcgga taactaatct ttcttattac agaatttttt agacgcacag cccaggccaa ctttgacgjta tcgggatacc aaagcatgta tgaagtcatt ggctcgaa ta tggagtcgag cggatttttc- cgcataaccg attcgtttta cgtcgtcatg cgtattatat ttgcagcata tacacgttcg ggaaaagtac aaaaagggtc gattaaagaa gaaatattca gtcttatccc 120 180 240 300 360 420 480 540 600 660 tgtcgg-gtta tgcctttagg cttqttgcca tagcgacacc gacctgaccg cgccaggcgc 720 aggcticaag gtttttatgc atagcaicat cgctaccact aaccagaatg gaagcgictg 780o '6aagacgg tt gataaataaa tttgctggca aaccctacac gaagtcgatg cttctgtctt 840 taggagaagc ac-ggaaagig aaaacggttg caatcaggtg cttaatccat gagccagtgt 900 gctgaacgat accgggattc tgttgtcgga atggcaggtt atccattaaa atagatcgga 960 tcgatataag cacacaaagg gggaagtgct tactaattat gaaacataaa ctacaa atg 1019 Met atg aaa aig Met Lys Met tct, ica agc Ser Se: Se: cgt Arg tgg ttg agt got Trp Ldu Sex Ala goa Al a 10 gta atg tta acc ctg tat aca Val Met Leu Thr Leu Tyr Thr 1067 tgg got ttc agt Trp Ala Phe Ser att Ile 25 gat gat gic gca Asp Asp Val Ala aag Lys Caa got caa Gin Al1a Gin 1115 tco tta Ser Leu goc ggg aaa ggc Al1a Gly Lys Gly t at Tyr gag gcg ccc aaa Glu Al1a Pro Lys aac ttg ccc tec Asn Leu Pro Ser gtt Vai ttc cgc gat atg Phe Arg Asp Met aaa Lys 55 tac gcg gac tat Tyr Ala Asp Tyr cag Gin cag atc cag ttt Gin Ile Gin Phe 1163 1211 1259 cat gac aaa gcg His Asp Lys Ala tac Tyr tgg aac aat ctg Trp Asn Asn Leu acc coa ttc aaa Thr Pro Phe Lys ctc gag Leu Giu s0 ttc tac cat Phe Tyr His gtg act gcc Vai Thz Ala 100 ggt atg tac ttc Gly Met Tyr Phe gat Asp aco cog gtc Thr Pro Val aaa ata aat gaa Lys Ile Asn Glu ccg gat tat ttc Pro Asp Tyr Phe 110 1307 1355 acc gca gtc aaa Thr Al.a Val Lys ato aaa tac ago Ile Lys Tyr Ser act ttc Thr Phe 115 ggc gat gtt Gly Asp Val cag cat GIn His 120 gac aaa gao acg gta aaa gac ctt ggt Asp, Lys Asp Th: Val Lys Asp Leu Gly 125 1403 ttt gcc ggt ttc aaa Phe Ala Gly Phe Lys 130 gtg Val 135 ott tao cog atc aac ago aaa gat aaa aac Leu Tyr Pro Ile Asn Ser Lys Asp Lys Asn 140 1C 1451 gaa atc gtc Giu Ile Val aig ctc ggg gc Met Leu Gly Al1a ago Ser 155 tat ttc cgo gig att ggt Tyr Phe Arg Val Ile Gly 160 1499 gca ggt cag Ala Gly Gin gcc ttg oca Al1a Leu Pro 180 tall ggc ott tot Tyr Gly Leu Ser gca Al1 a 170 cgc ggc ctg gca Arg Giy Leu Al1a att gat act Ile Asp Thr 175 tic igg atc Phe Trp Ile 15 47 1595 tag ggt gaa gaa Se: Gly Glu Giu cca cgc tic aaa Pro Arg Phe Lys gag Gi u 190 gag cgt Giu Arg 195 cca aaa ccg act Pro Lys Pro Tb.r aaa cgt tta acc Lys Arg Leu Thr att Ile 205 tat gca ttg ott Tyr Ala Leu Leu tag ccg cgc gcg Sex Pro Arg Ala a ca Th: 215 ggt got, tac aaa Gly Al1a Tyr Lys gta gtt atg cca Val Val Met Pro gga Gi y 225 1643 1691 1739 1787 cgt gac acg gt Arg Asp Th: Val gat gtg cag tog Asp Val Gin Se: aaa Lys 235 ato tat ctg cgc Ile Tyr Leu Arg gat aaa Asp Lys 240 ttt ggg Phe Gly gtc ggc aaa Vai Gly Lys cag aac oaa Pro Asn Gin 260 ctg Leu 245 ggg gtt gca cog Gly Vai Al1a Pro tta Lau 250 aco agt atg tic Thr Ser Met Phe ctg Leu 255 cog tog cot gca Pro Se: Pro Al1a aat Asn 265 aac tat cgt oog Asn Tyr Arg Pro gag Glu 270 ttg cac gao Leu His Asp 1835 tot aac Se~r Asn 275 ggt ctg tct ato Gly Leu Sex Ile got ggt aat ggc Al1a Gly Asn Giy tgg atc tgg cgt Tr-p Ile Trp Arg ttg aat aac cog Leu Asn Asn Pro aaa Lys 295 cat tia gcg gtc His Leu Al1a Val a go Ser 300 ago to tog atg Ser Phe Se: Met 1883 1931 1979 aac cog caa ggc Asn Pro Gin Gly ggt cta ttg cag Giy Leu Leu GIn ogt Arg 315 ggt cgt gat tic Gly Arg Asp Phe too ogo Ser Arg 320 ttt gaa gat Phe Giu Asp ctc Leu 325 gat gat Asp A-sp ogt tao gat Ar-g Tyr Asp 330 ott cgt oca ago Leu Axrg Pro Ser gca tgg gtg Al1a T -p Val 335 2027 act cog aaa ggg gag tgg ggc aaa ggc a;c git gag cig gig gaa ait Lys Gly Ser* VaX G2.u Leu va.i .L±e 2 0'75 Thr Pro Lys 340 G2.y Glu Trp Gly 345 Gly Ser Val Glu 350 Val Glu Ile eca acc Pro Thr 355 aac gat gaa ae Asn Asp Glu Thr aac Asn 360 gat aac ate gtc get Asp Asn Ile Val Ala 365 tac igg acg cc; Tyr Trp Thr Pro gat Asp 3'7 0 cag ci; cc; gag GIn Leu Pro Glu cog Pro 3.75 ggct aaa gag aig Gly Lys Glu Met itt aaa tac ace Phe Lys Tyr Thr

221.9 ace tie age cgt Thr Phe Ser Ar; gat Asp 390 gaa gac aaa ct; Giiu Asp Lys Leu go; cca gat aac Ala Pro Asp Asn goa tgg Ala Trp 400 gig caa caa Val GIn GIn aeg cgt Thr Ar; 405 cgt tea ac; Arg Ser Thr ggg Gly 4210 gat gig aag cag Asp Val Lys GIn tog aac ci; Sex Asn Leu 42.5 ttt aco ggo Phe Thr Gly 2261 ait cgc Ile Ar; get gag Ala Giu 435 cag Gin 420 cci gac ggt act Pro Asp Gly Thr a to Ile 425 gcc tii gig gic Ala Phe Val Val gat Asp 430 at; aaa aaa ci; Met Lys Lys 2Leu oca Pro 440 gag gat ace cc; Glu Asp Thr Pro gtc Val 445 aca go; caa acc Thr Ala GIn Thr

231.5 2363 24.2 2459 ati ggt gat aat Ile Gay Asp Asn ggt Gi y 455 gag aia git gaa Glu Ile Val Glu ac; gig cgt tat Thr Val Ar; Tyr cog git ace aaa Pro Val Thr Lys ggc Gly 470 ig; cgt ci; gig Trp Ar; Leu Val at; Met 475 ogi gig aaa gig Xr; va. Lys Val aaa gat Lys Asp 480 gee aa; aaa Ala Lys Lys ac; ti; agi Thr Leu Ser 500 ace Thr 485 act ;aa at; cgi Thr Giu Met Ar; get Al a 490 go; ci; gig aai Ala Leu Val Asn gee gat cag Ala Asp GIn 495 2507 2549 gaa ace igg age Giu Thr Trp Ser tao cag tta cci T yr GIn Leu pro 505 gcc aai ;aa Ala Asn Glu 51.0 taagaeaact ;agtacatig aegcaaigte caicgeegca agegagaaag eggeatigoc 2609 gaagactgat atccgceg ticaicaggc geiggaigec ;aaeaccgca ccigggc 2669 ggaggia acttgC'.gat agaagtaaaa c-tgggat~Cgc agagcaggag gateCtoaCg tcaggggtgg tatgcagctt ctgttgggtg gtcgcgataa atcgecggc tgcgtgcaac ttcttagtga tiatcgctga agcgtaaaag tggtggtgct tgatggaagc atacactgta ccggtttgca 9cgtgaaacc ccogttcaat gggictggal atgagcai t ggtqaa gg tccccgcaag ggacagttaa cgctccicga ctgcgtggaC agtgagcaaa ctcgcgcaaa gcgctgatta ctgecttata tccgccggat atacagtaia gttgatcatg gtgggaatca cagttataac agtcggtggc cggiaatatc ggatgCtgac caacccgaaC tgcgcgctgl cttctggcai gtttatcgai cctgtcaca' igcttaca i acgtgaceq iatgcaccc gctcggtaaa ttaaaaacga ggcgcgtctg cgaagggcgc gaacaagCct gatca gctaa aoccaaattc 2729 aggcgatgcc 2789 igtttcccga cccgtggcgt accaaCCcgg iaggccgttt6 2849 gcgatgtgac agtggcgiac ctgiigtcgc atcctatgga tgctgcaaac tctggaccgg tctgcgtcaa ccta tcigta giaaaagcca ccggatatet gaaggtcaga gatgactict tcggiaatga -gccgggateg cagcagttcc a cttggcgagi y cactgtgcai t gacttcgtg. t ctcccgggt c cgctggtgc g gttcaccgt gccgcgctat ctggctcgtt tgaccaaaga 2909 cgicggtacC a gacctggtat a taiggttggt c cggtatcctg a cgttgatgg cagttggega acgaagacgt ccgggaatgc gcgtcgcaga tvttctatcg gccgtcgctg ccggtgattg Ittcagtcgtc egacccgcgt L. cgcaciactg :tggctccgci g aagcggcgtt tccgccgti a( tgaagacca t :aggatgtgt g tcctctttg c :t tcctgcaa c tgaaOcatta a gaaccagtgit t caaacatttt gcaaaaagcc ccgcc~gc I gggcagcr-ag tttggcggc gcccaaagcg gtatgggcca ggggcataac gccgggcgaa gatgcgccgt :attctgt-t 2 tcttcctta 3 ggtticctt 3 ggtactgtt 3 tgcttattg3 *acccggagc :tigctggct ;atgtctaca :ggatggagc cgtcgcgtga tacagctaca ctggtgcgcc tccggcatgg ctgtttacag acgattatc ggttcttttg gcaggttggg 969 029 089 .149 5209 ~269 M 39 3389 3449 3509 3569 3629 3689 3,749 3809 3869 3929 3989 cttatgaaga attaccgcct aacttgctig acggtaacct cggtgttcCt gaigaactt gacgggcgtg cgtctgttCC atgtcttate 4049 4109 tctccgctcc gctgtggttt atgttCCt~cg Cgctctctac tgcattgcag gtagtacatg 4169 cgttgaccga accgcaatac ttcctgcaac cacggcagtt gttcccggta tggccgcagt 4229 ggcgtcctga gctggcgatt gcacttttig cttcgaccat gg-.gctgttg ttcctgccga 4289 agctattgag cattttactt atctagtgea aaggaacgaa agaa 4333 <210> 2 <212.> 511 <212> PRT <213> Escherichia coli <400 Met I Thr Gin I> 2 Met Lys Met Ara 5 Ser Ser Ser Trp Ser Leu Ala Gly Trp, Leu Ser Ala Ala Phe Ser Ile 25 Lys Gly Tyr Glu Ala 10 Asp Val Met Leu Thr Leu Tyr Asp Val Ala Ala Pro Lys Lys Gln Ala Asn Leu Pro Ile Gin Phe Sex Val Phe Tyr Axrg Asp Met Asn His Lys 55 Trp, Ala Asp Tyr Gin Thr Asp Lys Ala Glu Tyr 70 G1 y Asn Asn Leu Pro Phe Lys Leu Phe TIyr Rls Gin Thr Met Tyr Phe Asp 90 Ile Thr Pro Lys Tyr Giu Val Thr Phe Thr Phe 115 Giv Phe Ala Ala Val Lys A.rg 105 Asp Val Lys Ile Asn Ser Pro Asp Tyr 110 Val Lys Asp Leu Asp Val Gin His 120 Leu Lys Asp Thr Giy Phe Lys Tyr Pro Ile 130 Asn A-sp Asn 140 Tyr Lys Asp Lys Glu Ile Val 145 Gly Ser 150 Tyr Leu Gly Ala Phe Arg Val Ala Gly Gin Val 165 Gly Leu Sex Ala 1,70 Gly Leu Ala le 175 Thr Ala Leu Ile Glu Arg 195 Pro 180 Ser Gly Giu Glu Pro Arg Phe Lys Giu Phe Tr-p 190 Tyr Ala Leu Pro Lys Pro Thr Asp 200 Lys Arg Leu Thr Ile 205 Leu Asp 210 Ser Pro Arg Ala Thr 215 Gly Ala Tyr Lys Val Val Met Pro Arg Asp Thr Val Asp Val Gin Ser Ile Tyr Leu Arg Lys Val Gly Lys Leu 245 Gly Val Ala Pro Th: Ser Met Phe Leu Phe 255 Gly Pro Asn Asp Ser Asn 275 Pro Ser Pro Ala Asn 265 Asn Tyr Arg Pro Glu Leu His 270 Trp Ile Trp Gly Leu Ser Ile Ala Gly Asn Gly Glu 285 Arg Pro 290 Leu Asn Asn Pro Lys 295 His Leu Ala Val Ser Phe Se: Met Glu 305 Asn Pro Gin Gly Phe 310 Gly Leu Leu Gln Gly Arg Asp Phe Se: 320 Arg Phe Giu Asp Leu 325 Asp Asp Arg Tyr Asp 330 Leu Arg Pro Ser Ala Trp 335 Val Thr Pro Gly Giu Trp Gly Lys Giy Ser Val Giu Leu Val Glu 345 350 Ile Pro Thr 355 Asn Asp Giu Thr Asn 360 Asp Asn Ile Val Ala 365 Tyr Trp Th: Pro Asp 370 Gin Leu Pro Giu Pro 375 Gly Lys Giu Met Phe Lys Tyr Th: Thr Phe Ser Arg Asp 390 Glu Asp Lys Leu Aa Pro Asp Asn Trp Val Gin Gin Arg Arg Ser Thr Gay 410 Asp Vai Lys Gin Se: Asn 415 Leu Ile Arg Gin 420 Pro Asp Gly Th: Ala Phe Val Val Asp Phe Thr 430 Gay Al.a Gliu Met Lys Lys Leu Pro Glu Asp Thr Pro Val Thr Ala Gin 435 Thr Sex Ile 450 Asn Pro Val 465 Gly Asp Asn Gly Glu Ile Val Giu Ser Thr Val Ar; Tyr Thr Lys Gly 470 Trp Axg Leu Val Met A.rg 4*7 Val. Lys Val Ausp Ala Lys LYS Thr 485 Thr Glu Met Arg Ala Ala 490 Leu Val Asn Ala Asp 495 Gin Thr Leu Ser 500 Glu Thr Trp, Ser Gin Leu Pro Al1a Asf Giu 510 <210> 3 <211> 5.74 <212> DNA <213> Esckierichia coli <400> 3 ttcgiigatc acCaaacgct taata ccgat cgcggtgttt coccagcaag acCagagaag ccgt.ctgcat coaagggata acuiagttgc ttgcaagatt ctgtcaccgt ggaaactgtt cggttcctt &accgt.Cat gtgctggaaa cigaatcgcg ttccgcgtct aagctcaatc ctgatgcgct ttgiaggtcg itgttcggtt attteCageC ccctgatccc agatgaatcg ttaacgetct icgcccgtga atcgtcgcct ggaaticccc cactggcatt" acgettatca gataaggcgt ggaagagtat tcaaigCtcC ggcaaccgea ccgccacgtt ggtgcigcta ggagagatat gcgiaaaccg ggcctacatc teac gtgccaccgt tcacCgCCgC cttgaigatq atggcgaccg gaacaggcgc agcgatCCgg tct-tcatgg gaigcggctt gttctocaa tggtctgcga a ggtgctggt gttttagCa cgcgtcaccg tgaacgagac tgaegatgc tgagttatta cgcaaiaaaa tttattgatt 120 180 240 300 360 420 480 540 5.7 4 <210> 4 <211> 1478 <212> DNA <213> rEscherichia coliA <220> <221> CDs <222> (1449) <400> 4 gggataatgc ctgaggggr-c tgta at; cgt atc ggc at; Cgg ttg tig ctg Met Ar Ile Gly Met Arg Leu Leu Leu ogc tat ttt tta ctg gtg geg gtg gcg gec tgg ttc Gly Tyr Phe Leu Leu Val Ala Val. Ala Ala Trp Phe gta cig gct Val Leu Ala tit gtc aaa gaa Phe Val Lys Giu git aaa Val Lys ccg ggc gtg Pro Gly Val aga gca ac A.rg Ala Thr tta atc gac Leu Ile Asp cte tct ggg Leu Sex Gay ace Thr gca acg tig ctg gcg gag cig gcg cgt Ala Thr Leu Leu Ala Glu Leu Ala Ar-g .50 gag ggg acg Giu Gly Thr ccc gat tig Pro Asp Leu ttt aat cag Phe Asri GIn 147 gac eca acg cat Asp Pro Thr His caa ctg gcg cag Gin Leu Ala Gin cta caa Leu Gin cat cge cc; ttt His Ar-g Pro Phe cgc Ar g 90 gcc aat ate 9ggt Ala Asn Ile Gay 9gC Gay as att aac aaa gtg Ile Asn Lys Val cgc Arg aac gaa tat cat Asn Gilu Tyr His gtc Val 95 tat atg aec gat Tyr Met Thr Asp cag ggc aaa gia Gin Gly Lys Val ttg Leu 105 tic cat icg gca Phe Asp Ser Ala aat Asn 110 acg Thr aaa gec gtt gga Lys Al1a Val Gay tig cgt ggt cag Leu Ar; Gay Gin 130 gat tat tcg cgc igg aat Asp Tyr Ser Arg Trp Asn 120 gac gtc tgg Asp Val Trp caa aat cct Gin Asn Pro 140 cia Leu 125 tat ggt Tyr Gay gcg Al1a ege agc acg ttg Arg Ser Thr Leu 135 gec gat ccc gaa Ala Asp Pro Glu a gi Ser 145 tet gtg at; tat Ser Val Met Tyr gt Val 150 gcc geg ceg Ala Ala Pro att atg Ile met 155 gac ggc teg c9g Asp Gay Ser Arg ct Leu 160 att ggc gtt t; le Gly Val Leu age Ser 165 gia ggc aaa cc; Val GJly Lys Pro aac geg gcg at; Asn Ala Ala Met 170 gct cc; gtc att aag cgt Ala Pro Val Ile Lys ALrg 175 a gc Ser 180 gag cgg cga. att Giu Arg Ar Ile tta Leu 185 tgg gcc age gee att. tig ttg Trp, Ala Ser Ala le Leu Leu ggg att gca ct; gtg att ge gca ggc Gly Ile Al1a Leu Vai Ile Gly Ala Gly atg gtt tgg Met Val Trp gat tee gtc Asp Ser Val 220 ate aac cgc tet Ile Asn Arg Scr ati Ile 210 gcc agg etc act Ala Arg Lieu ThX cgc tat get Arg Tyr Ala 215 cte ggt agt Leu Giy Ser 6*75 723 act gac aat aag Thr Asp Asn Lys ccc Pro 225 gtt cet etc ec Val Pro Leu Pro age gag Sex Glu -235 ttg egt aaa etc Leu Arg Lys Leu geg Ala 240 eag geg ctg gaa Gin Ala Leu Giu a gt Set 245 atg cge gtg aag Met Arg Val Lys ct g Leu 250 gag Giu gaa ggg aaa aac Giu Gly Lys Asn cta aaa agec ca Leu Lys Ser Pro 270 tat Tyr 255 att gag eag tat Ile Giu Gin T1yr gt Val 260 tat geg tta act Tyr Ala Leu Thx ctg geg geg att Leu Ala Ala Ile cgt Axrg 275 ggc geg geg gaa Gly Ala Al1a Glu att tia le Leu 280 Cge gaa ggt Arg Giu Giy ctg acg eaa Leu Thr Gin 300 ceg cog gaa gig Pro Pro Giu Val get cgt tit ace Ala Arg Phe Thr gac aac at Asp Asn Ile 295 ita eta cgc Leu Leu Arg aat geg ega aig Asr Ala Arg Met cag Gin 305 gca ctg gig gaa Ala Leu Val Giu acg Thr 310 cag qca Gin Ala 315 aga ctg gag aat Axg Leu Giu Asn o gt Arg 320 eag gaa gte gt Gin Glu Val Val ctg Leu 325 act get qtt gat Thr Ala Val Asp gtg Val 330 gcg gca tta tt Ala Al1a Leu Phe ege A.rg 335 cge gte age gaa Arg Vai Ser Giu geg Al a 340 ege ace gtg eag Arg Thr Val Gin 1011 1059 1107 1155 gea gaa aaa aae Ala Giu Lys Asn ate Ile 350 act ttg eat gtt Thr Leu His Val aig Met 355 cci act gag gtt Pro Thr Glu Val aac gt Asr Vai -360 ctg gat 1,eu Asp gct tet gaa Ala Ser Giu ceg Pro 365 geg tta ctg gag Ala Leu Leu Giu cag Gin 370 geg ctg ggg aat Ala Leu Giy Asn tta Leu 375 aae gee ate gat ttt act ccc Asn Ala Ile Asp Phe Thr Pro gag age ggt tge ata aeg eta age gee Glu Ser Gly Cys le Thr Leu Ser Ala 1203 385 390 gaa gig Glb Val 395 gat cag gaa tac Asp Gin Glu Tyr gic Val 400 ace ctt aag gig cig gat acec gt agt Thr Leu Lys Val Leu Asp Thr Gly Ser 405 1251 ggg Gb y 410 ati ci gac tac lie Pro Asp Tyr gcg Al a 415 ctg tea cgjt at Leu Ser Axg Ile iii Phe 420 gaa cgc ttt Glu Arg Phe tac tct Tyr Ser 425 gcg ttt Ala Phe 440 1299 1347 ttg ccg cgt gca Leu Pro Arg Ala ggg caa aaa agc Gly Gin Lys Ser 9gt ctg ggg ttg Gly Leu Gly Leu gtc agt gag Val Ser Glu gtg cag gaa Val Gin Glu 460 gtc Val 445 gcc cgt ttg tt Ala Arg Leu Phe aac Asn 450 ggc gaa gtc acg Gly Giu Val Thr ctg cgc aac Leu Arg A-sn 455 ccgt cac tic A.rg His Phe 1395 1443 ggt 9gc gig ctg Gly Giy Val Leu teg cii cga ct Ser Leu Arg Leu cac His 470 aca tag cticaaattc ttcccacata gteiicgta Thr 475 <210> <2i1> 474 <212> PRT <213> Escberichia coi 14768 <400> Met Axg Ile Gly Met Arg Leu Leu Leu Gly Tyr Phe Leo Leo Val Ala Vai Ala Ala Gly Val Arg Phe Val Leu Ala Ile Phe Val Lys Glu Val Lys Pro Al1a Thr Leu Arg Ala Thr Glu Gb y 40 Thr Leu Ile Asp Thr Leu Al1a Giu Leu Ala Arg Asp Leo Leu Ser Gi y Asp Pro Thr His Gb y Gin Leu Ala Gin Ala *70 Phe Asn GIn Leo Gin His 75 Arg Pro Phe Arg Ala Asn Ile Met Tkr Asp Val Gly Gin 115 Gly Gin Tyr Gly Gay Ile Asn Lys Val Arg Asn Giu Tyr His Val Tyr 90 pla Gin Giy Lys Val Leu Phe Asp Ser Ala Asn Lys Ala 100 Asp Tyr Ser Arq Trp 120 Thr Asp Val Trp Leo 125 Ala 110 Thr Leu Ar; Asp Pro Glu Gly Ala Ar; 130 Ser Ser Ser 135 Ala Leu Gin Asn Pro 140 Asp Val Met Tyr 145 Ile val 150 Val Ala Pro Ile Met 155 Ala Gly Se: Arg Leu 160 Gly Val Leu Gly Lys Pro Asn 170 Trp Ala Met Ala Pro Val 175 lie Lys Ar; Gly Ile Ala 195 Ser Ile Ala Ser 180 Leu Ar; Arg Ile Leo 185 Giy Ala Ser Ala Val Ile Gly Ala 200 Tyr Met Val Trp Trp 205 Thr Ile Leu Leu 190 le Asn Ar; Asp Asn Lys Ar; Leu Thr 210 Pro Val Ar; 215 Leo A.a Asp Ser Val 220 Leu Pro Leo Pro Asp 230 Met Gly Ser Ser Glu 235 Arg Lys Leo Ala 240 Ala Leu Glu Ser 245 Tyr Ar; Val Lys Leu 250 Giu Gu Giy Leo Lys Lys Asn Tyr Ile 255 Glu Gin Tyr Ala Ile Arg 275 Val Val Ala Val 260 Gby Ala Leo Thr His 265 Leu Ser Ala Ala Glu Ile 280 Arg Giu Gly Pro 285 pro Leu Ala 270 Pro Pro Glu Ala Ar; Met Ar; Phe Thr 290 Gin Ala 305 Gin Glu Asp Asn 295 Ile Leo Thr 3n Asn 300 Leo Vai Glu Thr Leo Leo Ar; Gin 310 Val Vai Leo Thr Ala Val Asp Val 325 330 A.1a 315 Ala Arg Leu Glu Asn Ar; 320 Ala Leo Phe Ar; Ar; 335 Val Ser Glu His Val Met 355 A.rg Tb: Val Gin Leu 345 Ala Gliu Lys Asn lie Th: Leu 350 Ala Leu Leu Pro Th: Giu Val Asn 360 Val Ala Sex Glu Giu Gin 3710 Ala 1,eu Gay Asn Leu 375 Leu Asp Asn Ala Asp Phe Tb: Pro Glu Ser Gly Cys Il~e Leu Ser Ala Glu Val 395 Asp Gln Glu Tyr Th: Le1u Lys Val Asp Thr Gay Se: Gly 410 Ile Pro Asp Tyr Ala Leu 415 Se: Arg Ile Lys Se: Ser 435 Glu Arg Phe Tyr Ser 425 Leu Pro Arg Ala Asn Gay Gin 430 Ala Arg Leu Gly Leu Gay Leu Al1 a 440 Phe Val Ser Giu Phe Asn 450 Gly Glu Val Tb: Arq Asn Val Gin Gly Gly Val 1,eu Ala Se: Leu Arg Leu 465 <210> 6 <211> 128 <212> DNA. <213> Escherichia ci <22 0> <221> CDs <222> (126) His 470 Arg His Phe Thzr 0 1i <400> 6 atg aaa Met Lys 1 git ggc Vai Giy ggt cgc ctg Gay Arg Leu 5 gea gog ct Ala Al1a Leu tta gat gct gtc Leu Asp Ala Val ceg Pro 10 ctc agi tcc cta acg ggc Leu Se: Se: Leu.Th: Gay agt aac aag Sex Asri Lys ctg Leu gcg aaa atc aac Ala Lys Ile Asn cat act 96 His Tb: gia cag gat tta tc tta cac cit ci ctg cg Val Gin Asp Leu Leu Leu His Leu Pro Leu <210> *7 <211> 42 <212> PRT <213> Escherichia coli <400> 7 Met Lys Gly Ar;q Leu 1 5 Leu Asp Ala Val Leu Ser Ser Leu Thr Gly Leu His Thr Val Gly Ala Val Gin A.sp Ala Leu Ser Asm Lys Leu 25 Ala Lys Ile Asn Leu Leu Leu His Leu Pro Leu <210> e <211> 1174 <212> DNA <213> Escherichia. coli <22 0> <221> CDS <222> (837) <400> 8 agatgcacga tcgagtaggc eggataaggc gtttacgccg catccagcat ggaaaacgcg cact.ttgtta tcaatctggg gccagcaaat gctggcctga tttgttcttg agggaagact 120 at; Met I aig cgc aaa at; ctg ct; Met Ar;g Lys Met Leu Leu 5 gc; gca 9ca ct Ala Ala. Ala Leu 10 t~c agc gtC aeg Cys Ser Val Thr ica gt; ac; gca at; 5cr Val Thr Ala Met acc gct cac Thr Al1a His gac tac cag Asp TIyr Gin ccg cgt gac gat gig 216 Pro Ar; Asp Asp Val att aic agc Ile Val Sex ccg caa acc gig cag gig aag ggc gaa aac ;gc aat ci; Pro Gin Thr Val Gin Val Lys Gay Glu ;Lsn Gly Asn Leu gig ktc acg cca gac ggc aac gig atg tat aac ggt aag caa tat icc Val Ile Thr Pro Asp Gly Asn Val Met Tyr Asn Gly Lys Gin Tyr Ser cig Leu cgt kr g aat gee gee cag Asn Ala Ala Gin cgc A.rg gag cag gcg aag Giiu Gin Ala Lys tat cag gct gaa Tyr Gin Ala Glu age ace cig Ser Thr Leu tgg att gat gga Tr-p Ile Asp Giy geg aaa age cgc Ala Lys Ser Arg gte gag Val Glu aaa get cgt Lys Ala Arg age agc aaa Ser Ser Lys 115 att Ile 100 geg etg gat aaa Ala Leu Asp Lys at le 105 ate git cag gag Ile Val Gln Giu aigq gge gaa Met Giy Glu 110 cag cig aaa Gin Leu Lys aig egc age cg. Met Arg 5cr Arg etgq Leu 120 aec aaa ett gat Thr Lys Leu Asp gag cag Giu Gin 130 aig aac egc at Met Asn Arg Ile ate Ile 135 gaa aeg cge age Giu Thz Arg Ser ggc ctg aeg ttt Gly Leu Thr Phe eac His 145 tat aaa gee att Tyr Lys Ala Ile gat Asp 150 cag gtt cgi gee gaa gge cag caa tta Gin Val Arg Ala Giu Gly Gin Gin Leu 155 aat, cag gca atg Asn Gin Ala Met gga att tta eag Gly Ile Leu Gin age att aat gaa Ser Ile Asn Glu aig ggc Met Gly 175 geg aaa geg Ala Lys Ala gga age ctg Gly 5cr Leu 195 gtg Val 180 ctg aaa age ggc Leu Lys Ser Gly ggt. Gly 185 aae eca tta cag Asn Pro Leu Gin aae gig etg Asn Vai Leu 2.90 igg aaa aag Trp Lys Lys ggc gge cig caa Giy Giy Leu Gin tee Ser 200 tea ate Caa &ce Ser Ile Gin Thr gag Giu 205 cag gaa Gin Giu 210 aaa gat tte eag Lys Asp Phe Gin ca g Gin 215 itt ggc aaa gat Phe GI y Lys Asp tgt age cge gt Cys Ser Arg Vai gig Val 225 act ctg gaa gat Thr Leu Giu Asp age Ser 230 egc aaa gee ctg ALrg Lys Ala Leu gte Val 235 ggg aat tia aaa Gly Asn Leu Lys taateeteta tttiaagacg geataatact tittatgce gtttaattci tcgttttgtt 897 acctgccict aactttgtaa gggcgaattc tgcagatatc caicacactg gcggccgctc 957 gagcatgcat ctagagggcc caaticgccc taiagtgagt cgtattacaa t-tcactggcc 101)7 gtcgttttac aaccg-tcgtg actgggaaaa ccct-ggcgtt acccaactta atcgccttgc 1077 agcacatccc cetttcgcca gctggcgtaa tagcgaaaag gcccgcaceg atcgcccttc 1137 caaCagttgC qcacctgatg gccaatggac gcgcctg 11"74 <210> 9 <211> 239 <212> PRT <2i3> Escherichia coli <400> 9 Met I Thr Met Arg Lys Ala His Ala Val Ser Pro Leu 1,eu Ala Ala Ala Leu Ser Val Thr Ala Met Tyr Gin Cys Ser 25 Val Val Thr Pro Arg Gin Thr Val Lys Gly Giu Val Ile Thr Asn Lys Asp Asp Vali Gly Asn Leu Gin Tyr Ser Pro Asp Gly Met Tyr Asn Leu Asfl Gi y Tyr Ala Ala Gin Arg Arg 70 Trp Gin Ala Lys Asp Al a Gin Al1a Giu Sex Thr Leu Ile Asp Gly Gly Ile Lys Sex Arg Val Giu Lys Ala Azg Ser Sex Lys 115 Glu Gin Met 130 Leu Asp Lys Ile 105 Thr Val Gin Giu Arg Ser Argj Leu 120 Gliu Lys Leu Asp Ala 125 Gi y Met Gly Glu Gin Leu Lys Leu Thr Phe Asn Arg Ile Ile 135 Thr Arg 5cr Asp 140 His Tyr Lys Ala Ile Asp Gin Val Arg Ala Glu Gly Gin Gin Leu Val 145 150 155 160 Asn GIn Ala Met Gly Ile Leu Gin Ala Lys A-la Gly Ser Leu 195 Gin Glu Lys Va~l Gi y Lys 5cr Gly Gly 185 Sex Asp 1,70 Asn Ile Ser Ile Asn Glu Met Gly 175 Pro Leu Gin Asn Val Leu 190 Gin Thx Glu Trp Lys Lys 205 Asp Val Cys Sex Axrg Val Gly Leu Gin Ser 200 Phe ALsp Pkie Gin Gin 215 Ar-g Gly Lys 220 Gly Leu Giu Asp Ser 230 Lys Ala Leu Asn Leu Lys <210> <211> 3406 <212> DNA <213> Escherichia co. <220> <221> CDS <222> (1007) (1276) <220> <221> CDS <222> (1280) (1792) <220> <221> CDS <222> (1798).. (2574) <220> <221> CDS <222> (2604).. (3398) <400> ii gaigatggig aaacggcacc ctttcgcgac acacccggaa agaagafaaa atggagcgta tttacggcai tccggtgtct gatgttgcga cgctggagaa aacatgaaat tgctggcgga acgcggcgtg caggtgttei tcactcaggt 120 agctttttcc atgctgaiat gcaccctggc aacatcttcg taagctatga 180 aacccgaaat atatcggcat tgattgcggg attgttggct cgctaaacaa 240 cgctatctgg cggaaaactt taicgcctte tttaaicgcg actatcgcaa 300 117 agtggcagag ctacacgicg attctggttg ggtgccacca gataccaacg tigaagagtt 360 cgaaiitgct aticgiaCgg tctgtgaacc gttt~ggaCat gccgcaactg ttatccgcaa tcaggicggt aaaaatgca gcatagtgtt cgcgttattt agccgacctg ttgtc-cggt gtactgtiaa gtgtta ctcC ctcgatitat attCCtgCgC gaactgcctg g gi a ga ttg tctcagaatt aatgggggct tggcgcaaaa atctgtttaa agaaaaccct ggaaaacgge tggtgagagc aaciggttia cccgcgagct ggcgctacgt gatgcCCggc iaictttgag tacggcgcgt gecttacgtC gaa gcCtttC atttaaagaa cgacagtttg tcagtcaaat tagtatttaa tggttaatgg aaaccgctgg cgcttcaata gaaggggiag ctggagtiogi aaagcgccgt cgccagggca catatacgtc gtggcacatt caggtggict ccgaaatttc iggaagtgca gacgccagct g gattaanga tctgggtr-ga agtatttaca agggacaati cttgtiggtc gatcgcctgg 420 480 540 600 660 "720 *78 0 840 900 960 1015 cacgctgatt ttttcaicgc tcaaggcggg ccqtgtaacg tataaigcgg ctttgtttaa tcatcaicia ccacagagga acaigt aig ggt ggi Met Gly Gly ate agt Ile Ser iii ggc Phe Gay att igg cag tia Ile Trp, Gin Leu tg Leu 10 att att gee gtc Ile Ile Ala Val acc aaa aag Thz Lys Lys gge icc atc ggt Gly Ser Ile Gly atc Ile ic 5cr 30 gat Asp aic git gin ctg ct le Val Val Leu 1,eu gat cii ggi gcg tcg Abp Leu Giy Ala Ser gaa oca aag cag gat Giu Pro Lys Gin Asp aaa ggc iii Lys Gly Phe aa Lys ga t Asp gca aig agc Ala Met Ser gat Asp 45 gcg Ala 1063 1111 1159 12 07 1255 1303 aaa acc age Lys Thr Sex cag gcg gat Gin Ala Asp gct gat ttt Ala Asp Phe act Thr aaa act atc Lys Thr Ile gcc gat aag Ala Asp Lys nat cag gaa Asn Gin Giu cag Gin 75 gct aaa ata gaa Ala Lys Ile Giu Asp Ala Lys Arg ggt itt agC gaa cac-gat aaa gag cag gig taa ict gig iii gat atc His Asp Lys Glu Gln Val Hi~sAsp ys Gu Gi ValVal Phe Asp Ile Gay Phe Ser Glu ggg cc; caa cga Gly Pro Gin Ar-g cig cia Leu Leu 100 tig gig tie atc Leu Val Phe Ile atc ggc Ile Giy 105 ctc gte gt Leu Val Val ctg Leu 110 cct gig gcg gia pro Val. Ala Val aaa Lys 120 acg gia go; ggc Thr Val Ala Gly ig; T rp 125 a-It cgc gcg tt; Ile Arg Ala Leu tea ci; go; aca Ser Leu Ala Thr gig ca; aac gaa Val Gin Asn Glu ci; Leu 140 acc ca; gag tia Thr Gin GlU Leu aaa c Lys Leu 145 14 47 eag gag ttt Gin Glu Phe aac ctg acg Asn Leu Thr 165 ca g Gin 150 gao agi ci;q aaa Asp Sex Leu Lys aag Lys 155 git gaa aag go; Val Glu Lys Ala ago etc act Ser Leu Thr 160 cgc cag got Arg Gin Ala 1495 1543 ccc gaa ct; aaa Pro Glu Leu Lys go; Ala 170 tog at; gat gaa Set Met Asp Glu tta Leu 17 go; gag Ala Giu 180 to; at; aaa egt Ser Met Lys Ar; tao gtt gca aac Tyr Val Ala Asn gat Asp 190 cot gaa aag go; Pro G2.u Lys Ala age Set 195 gat gaa go; cac Asp Giu Ala His ace Thr 200 ate cat aac ccg Ile His Asn Pro gtg Val 205 gig aaa gac aat Val. Lys Asp Asn gaa Giu 210 1591 1639 1687 act go; cat gaa Thr Ala His Giu 9gc Gi y 215 gia aeg cot got Val Thr Pro Ala got Al a 220 gca oaa aeg oag Ala GIn Thr Gin gee agi Ala Ser 225 teg cc; gaa Set Pro GiU get Cg gao Ala A.1a Asp 245 ca g Gin 230 aag eca gaa ace: Lys Pro Glu Thr ac; Thr 235 eca gag cogq gig Pro Giu Pro Val gia aaa cct Val Lys Pro 240 to; tog agt Ser Ser Set 1'735 1783 gct gaa cc; aaa Al1a Giu Pro Lys ace: Thr 250 got gca cot icc Al1a Ala Pro Set oct. Pro 255 gat aaa cog taaae at; tot gta gaa gat act caa cc; ctt ate ac; eat 1833 Asp Lys Pro Met Set Val Giu Asp Thr Gin Pro Leu Ile Thr His 260 265 270 ct; att gag ci; egi aag cgt ci; ct; aae tgo: ait ate teg gig ate 1881 Leu Ile Gin Leu Arg Lys Arg Leu Leu Asn Cys Ile Ile sex Val Ile .gt; at-a Val Ile 290 t-c ci; igi Phe Len Cys ctg gic tat tic gcc aat gac atc tat cac ctg 1.929 Leu Val Tyr Phe Ala Asn Asp 305 gt-a icc gc; oca Val Ser Ala Pro ctg Len 310 atc aag cag t-tg Ile Lys GIn Len cg Pro 315 caa ggt tca acg Gin Gly Ser Thr atg at-c Met Ile 320 1977 gCO aco gac Ala Thr Asp at-g gig tog Met Val Ser 340 gt-g Val 325 gee t-c; cc; tic Ala Ser Pro Phe acg cc; atc aag Thr Pro Ile Lys ctg acc ttt Len Thr Phe 335 cag gt-g tgg Gin Val Tr-p 2025 2 07 3 ctg att ct-g t-ca Len Ile Len Ser ccg gtg att ct-c Pro Val Ile Leu tat Tyr 350 gcg t-i Ala Phe 355 atc gcc cca gcg Ile Ala Pro Ala t-at aag cat gaa Tyr Lys Hi3 Gin cgc ctg gig gig Ar; Leu Val Val cc; pro 370 ctg ctg git- tee Leu Len Val Ser agc Ser 375 ict cig cig tt- Ser Len Leu Phe atc ggc aig ge; Ile Giy Met Al1a it-c Phe 385 2121 2169 221*7 gec tao itt gt-g Ala Tyr Phe Val gtc Val 390 it-t ccg cig goa Phe Pro Len Ala iii Phe 395 ggc t-t-c cit gcc Giy Phe Len Al1a aai acc Asf Thr 400 gcg cc; gaa Ala Pro Giu t-tc gt-t at; Phe Val Met 420 ggg Gi y 405 gia cag gia icc Val Gin Val Ser gac atc go; Asp Ile A-1a agc tat t-a agc Ser Tyr Len Ser 415 tit gaa gtg cog Phe Gin Val Pro 430 2265 2313 go; ci; t-i at-; Ala Len Phe Met 0; Ala 425 t-i ggt gic icc Phe Gly Val Ser qg ;ca Val Ala 435 at-i gig ct-g ci; Ile Val Leu Len t-gc t-gg Cys Trp 440 tat gig Tyr Val at-; ggg at-i ace tcg cca gaa gao Met Gly Ile Thr Ser Pro Gin Asp 445 ci; gt- ggi gca t-c git- gic ggg Len Vai Gly Ala Phe Vai Val Gly 460 465 2361 2409 ogo aaa aaa ogo Ar; Lys Lys Ar; cc; Pro 455 aig tig ctg ac; cc; cog gat gto it-c to; caa acg ci; go; atc 2457 Met Leu Leu Thr Pro Pro Asp Val Phe Ser Gln Thr Leu Leu Ala Ile cct atg tao pro Met Tyr a-It ggt aaa Val Gly Lys So0 tgc ci; Cys Leu 485 ttt gaa ate ggi gt tc tL-C ica cgc itt tac Phe Glu Ile Gly Val Phe Phe Ser Arg Phe Tyr 490 495 2505 ggg coa aac cgg Gly A-rg A-Sn Axg gaa gag gaa aac gao gct gaa gca gaa Giu Glu Giu Asn Asp Ala Glu Al1a Glu 505 510 2553 iaa attcaaCCgc ccgtc-agggc ggttgtcai age gaa Ser G1u 515 aaa act gaa gaa Lys Thr Glu Giu at; Met 2606 gag tac a;; Giu TYr A-rg gcg aaa gac Ala Lys ASP 540 at; Met 525 ttt gat ate ggc Phe Asp Ile Gly gtt aat t; ace Val Asn Leu Thr 530 go; ogc got tt Ala A r; Ala Phe agt tcog caa ttt 5cr Ser GIn Phe 535 2654 27 02 ogi gat gat gtt Arg Asp Asp Val gia. Vali 545 go; gga gt Ala Gly Va2. aat ggg Asn Giy 555 cta cic atc acc Leu Leu Ile Thr ggt Gi y 560 ace aat ctg cgt Thr Asn Leu Axg gaa ago cag cag go; Giu Ser Gin Gin Ala 565 ica acg go; ggc gta Se: Thr Ala Giy Val 2750 2798 2846 aag ctg go; cgi Lys Leu Ala Ar; ca 9 Gin 575 tat tog teo tgt Tyr Ser Ser Cys tgg Trp 580 cat oct caC gac His Pro His ASP age Ser 590 agc ca; ig; oaa Se: Gin Tzp Gin got Ala 595 gig act gaa gaa Val Tlhr Giu Giu go; at Ala Ile 600 att gag ci; Ile Giu Leu cto gao ttt Leu Asp Phe 620 go; ca; coa gaa Al1a Gin Pro Glu gig Val 610 gig go; att ggt Val Ala Ile Gly gaa tgt gg't Giu Cys Gly 615 gaa ogo got Giu Ar;j Ala 2894 2942 aao cgO aac ttt Asn Ar;g Asn Phe tog Ser 625 acg cog gaa gag Thr Pro Giu Giu oag Gin 630 itt gtt Phe Vai 635 goc cag ota ogo Ala Gin Leu Ar; gc gca gaa tia aao at; oo9 gta ttt Ala Al1a Giu Leu Asn Met Pro Val Phe 645 2990 at; *oac tgt ogo gat gcc cac gag gg itt at; aoa tig ci; gag cog 3038 Met Hi s *CyS Arg Asp Ala His Giu Ar; Phe Met Thr Leu 1.eu Gltu Pro tgg ci; gat aaa Trp, Leu Asp Lys cct ggt go; gt Pro Gly Ala Val cat igc itt acc His Cys Phe Tb: ggc aca Gly Tb: 680 3086 Coc gaa gag Arg Glu Glu at; Met 685 cag gcg i~c gig Gin Ala Cys Val igt gga att tat Cys Gly Ile Tyr aic ggc ati Ile Gly le 695 egg gaa t; Ar; Giu Leu 3134 ace ggi Tb: Gly t; cog Leu Pro tgg TrP 700 gt igc gat gaa Val Cys Asp GlU ogo ggg ci; gag -Ar; Gly Leu Glu ii; ait. cog gog Leu Ile Pro Ala gag Giu 720 aaa t; ci; atc Lys Leu Leu Ile act gat gog cog Thr Asp Ala Pro 3182 3230 3278 3326 tat Tyr 730 cig cio ct cgc Leu LeU Pro AX; ga t Asp 735 ciC acg eca aa; Leu Thr Pro Lys cca Pro 740 ica icc egg ogo Ser Se: Ar; Ar; aac Asn '745 gag eca gc cat GlU Pro Ala His ci; Leu 750 ccc cat att tig Pro His Ile Leui cgi ait geg cac Ar; Ile Ala His igg cgt Trp Ar; 760 gga gaa gat Gly Glu ASP aca ci;g ttt Tb: Leu Phe 18 0 gec Ala '765 gca ig; ci; got Ala Trp Leu Ala ace ac; gat 900 Thr Thr Asp Ala aat gic aaa Asn Vai Lys 7725 3374 3406 ggg ati, go; tt Gly Ile Ala Phe tag agtigcg <210> 11 <211> 89 <212> PRT <213> Escherick~ia ccli <400> 11 Met Gly Gly Ile Ser Ile Trp, Gib 1 5 Leu Leu Ile Ile Ala Val Ile Val 10 Val Leu Leu Pbe Gly Thr Lys Lys Leu Gly Se: Ile Gly Ser Asp Leu 25 Gly Ala Ser Ile Lys Gin Asp Lys Ala Asp Ala Lys Lys Gly Phe Lys Lys Ala Met Ser Asp Asp Giu Pro 40 Thzr Ser Gin Asp Ala Asp Phe Thr Ala Lys Thr Ile 55 Ala Asp Thz Asn Gin Giu Gin Ala Lys Ile Giu Asp 70 75 Asp Lys Giu Gin Val Lys Gin Arg His <210> 12 <211> 171 <212> PRT <213> Escherichia coi <400> 12 Val 1 Leu Phe Asp Ile Val Val Leu Giv Tr Ile Phe Ser Giu Leu Leu Val Phe Ile Ile Gly Pro Gin Ar; Leu 25 Ser Val Ala Val Ar; Ala Leu Giu Leu Th~r Ar; 40 Leu Leu Ala Thr Thr Asp Lys Thr Val Val Gin Asn Ser Leu Lys Gin Giu Leu Gin Glu Phe Lvs Val Gin Pro Giu Lys Ala Ser Ser 70 Thr Asn Leu Thr 75 S er Giu Leu Lys Ala Met Asp Giu Ar; Gin Ala Ala Giu Asp Met Lys Ar; Ser Tyr Vai Ala Asn Asn Pro Val 115 Ala Ala Ala 130 Asp 100 Val Giu Lys Ala Scr 105 Thr Glu Ala His Lys Asp Asn Giu 120 Ser Ala His Glu Gi y 125 Lys Thr Ile His 110 Val Thr Pro Pro Giu Thr Gin Thr Gin Al a 135 Ser Pro Giu Gin 140 Ala Thr Pro Giu Pro Vai Val Lys Pro Ala Ala 145- 150 Asp 155 Giu Pro Lys Ala Ala Pro Ser Pro Ser Ser Ser Asp Lys Pro 165 170 <210> 13 <211> 258 <212> PRT <213> Escherichia coli <400> 13 Met Sex Val I Arg Lys Arg Cys Leu Val Leu Ile Lys Ala Ser Pro Glu Leu Tyr Asp Leu Thr Gin Pro Leu Ile Thr His Leu lie Glu Leu Asn Cys Ile Ile 25 Ile Val Ile Val Phe Ala Asn Asp 40 Gly Tyr His Leu Val Ala Ile Phe Leu Ser Ala Pro Thr Asp Val Gin Leu Pro Phe Phe Thr 70 Ala Pro Val Gin 55 Pro Ser Thr Met Ile Phe Ile Lys Leu Ile Thr Val Met Val Ser Leu Se: Ile Leu Tyr Gin Leu Trp Ala Phe Ile Ala Pro Ala Leu Sex Ser Se: 115 Val Phe Pro Tyr 100 Leu His Giu Arg Arg 105 Gly Val Val Pro Leu Phe Tyr Ile 120 Phe Met Ala Phh Ala 125 Ala Leu Leu Val 110 Tyr Phe Val Pro Giu Gly Leu Ala Phe 130 Val Gln Gly 135 Ile Leu Ala Asn Thr 140 Se: Val Ser Thr Asp 150 Giy Ala Ser Tyr Phe Val Met Phe Met Ala Phe 165 Met Val Se: Phe Glu 170 Pro Pro Val Ala Ile Val 175 Lys Lys Leu Leu Cys Trp Gly Ile Thr Ser 185 Glu Asp Leu Arg 190 Arg P.ro Tyr Val Leu Val Gly Ala Phe Val Val Gly Met Leu Leu Thr 24 195 Pro Pro 210 Asp Val Phe Ser Gin 215 Thr Lou Leu Ala Ile Pro Met Tyr 220 Tyr Val Giy Lys Cys Giy Leu 225 Phe Giu Ile Gly Phe Phe Ser Arg Phe 235 240 Lys Thr 255 Arg Asn Arg Glu Glu 245 Glu Asn. Asp Ala Glu 250 Ala Giu Ser Glu Glu Glu <210> 14 <211> 264 <212> PRT <213> Escherichia coli <400> 14 Met Giu Tyr Arg Met Phe Asp Ile Giy Vai Asn Lou Thr Ser 1 5 in Ser Gin Phe Ala Lys Val Asn Giy Asp Arg Asp Asp Val Ala Arg Ala Phe Asp Ala Gly Ser Gin Gin Leu Leu Ile Thr Giy 40 Thr Asn Leu Arg Glu Ala Gin Lys Leu Ala A rg Gin Tyr Ser Se: Cys Se: Thr Ala Giy Val His Pro His Asp Ile Ile Giu Leu Ala Ser Gin Trp Gin Vhl Th: Glu Giu Ala Ala Gln Pro Glu Val 90 Val Ala Ile Gly Glu Cys Gly Leu Asp Ala Phe Val 115 Asn Axg Asn Phe Se: 105 Thr Pro Glu Glu Gin Giu Arg 110 Met Pro Val Ala Gin Lou Arg Ile Ala 120 Ala Giu Leu Asn 125 Phe Met 130 His Cys Ar; Asp Ala 135 His Gu Arg Phe Met 140 Thr Lou Leu Glu Pro.Trp Leu Asp Lys Leu Pro Gly Ala Val Lou His Cys Phe Thr Gly 145 Thr 150 Gln Arg Giu Glu Al1a Cys Val Al a 170 Arg Gly Ile Tyr Ile Gly 175 Ile Thz Gly Leu Leu Pro 195 Pro Tyr Leu Trp 180 Leu Cys Asp Giu Arg 185 Lys Gly Leu Giu Ile Pro Al1a Leu Leu Ile Glu 205 Ser Leu Arg Giu 190 Th.- Asp Ala Ser Arg Arg Leu Pro A-rg 210 Asn Glu Asp 215 Pro Thz Pro Lys Pro 220 Arg Pro Ala His 225 Azrg Lp-u 230 Al1 a His Ile Leu Ile Al1a His T rp 240 Val Gly Giu Asp Al1a 245 Gi y Trp Leu Ala Al1a 250 Thr Asp Ala Asn 255 Lys Thr Leu Phe 260 Ile Ala Phe <210> <211> 586 <212> DNA <213> Escherichia coli <220> <221> <222> (170)..(370) <400> tcttaaacaa ccgtcgcttt gcgccgccgc aattattatg tgattcacct tgttacagat tgctattgtg tgcgcgcgtc tggt-.tttaa ggcgcgttct gttgccggtt atatgtcaag atgttttttt actcggcgct gaa-tgaccgt taatattctc 120 aaggtatct atg ggt gag 178 Met Gly Glu 1 ctg gtc gtt ctg ctg 226 Leu Val Val Leu Leu gac ctt gga gcg gcc 274 ati agt att acc aaa ct9 ctg gia gjtt gcg gcg Ile Ser Ile Thr Lys Leu Leu Val Vai Ala Ala 10 ttt-ggg act aag aag tta cgt acg ctg ggc gga 26 Phe Gly Thr Lys Lys Leu A-rg Thr Leu Gly Gly Asp Leu Gly 25 30 att aaa ggg ttc aag aag gcg atg aat gat gac gat gct gcg Ile Lys Gly Phe Lys Lys A1a Met Asfl Asp Asp Asp Ala Al1a 45 aaa ggc gca gac gtt gat ctt cag gct gaa aag ctc tct cat Lys Gly Ala Asp Val Asp Leu Gin Ala Glu Lys Leu Ser His 60 tgacgtggcg agcaggacgc tcccicaata tcttgttcga tacaaaaac agcgggtttt ttatcagaca gatgtaagta attattacag gattacttaa tttcgcctgc aaatcggcgt ggtaagaaga gcggacaaac ggaccgcatg aaagcccatc gccagcgctt cgctttcatt tcgtcg A-la Ala gcg aaa 322 Ala Lys aaa gag 370 Lys Glu cgcttcaaaa 430 cttccatccc 490 cagcatgggt 550 586 <210> 16 <211> 67 <212> PRT <2 13> Eschericklia ci <400> 16 Met Gly Glu 1 Val. Leu Lau Gly Ala Ala Ala Ala Lys His Lys Giu Ile Ser Ile Thr Lys Leu Leu Val. 5 10 Phe Gly Thr Lys Lys Leu Arg Thr 25 Ile Lys Gly Phe Lys Lys Ala Met 40 Lys Gly Ala Asp Val. Asp Leu Gin 55 Val. Ala Ala Leu Val. Leu Gly Gly Asp Leu Asn Asp Asp Asp Al1a Ala Glu Lys Leu Ser <210> 17 <211> 4200 <212> DNA <213> Salmonella typbhimuriumf <220> <221> CDS <222> (947) (1444) <220> <221> CDS <222> (1450).. (1722) <400> 17 cgc-aagtcaa tgtcgtcccg ctaacaaaga ggoagogtga atcacagagg aacatgtatg tcgtcgtact gctgttcggc ctatcaaagg ctttaaaaag aggacgc-tga ttttaccgot acgCt.aaaag cc-aagataaa tgctgttagt gttcgttatc taaaaaoggt agcgggCtgg aactgactca ggaactgaaa cgagcctgga aaatctgact cggagtcgat gaaacgcacC ataccatcca taatccggtc, ccgccgctga aacacaggc, tgcctgagtc gacggaaac cgcctgttgt cgaatcttc gtcgtatgta aggataatgt ggtggtatca accaaaaaac gccaigagcg aaatctatcg gagcaggtat ggcctcattg *attcgcgcgt *cttcaggagt cccgaactga *tacagcgcta ;gtaaaaggga ;agcgcgcCg( C gcttccgtai c ccctcgtcg aaagtlatgtg gtataatgeg gtatttggca tcggttccat atgatgatgc cggataagca aatccgtgtt tgttggggcc tgcggtccct tccaggacac aagcatctal Lacgatcccg; iacgaaacgc; ;aacaaaagc ;ccacgatag a gtgataaac aataggggg gccctaataa gttgttgati cggttCCgat c a aaca gg at aggcgaagcg tgatatcggt gcaacgattg tgcgacaacg tctgaaaaaa ggatgaacti i acaagcgagc a gcatgagggc ggagcccgt' a cgccgagaa gtaaac at Me gcgaaagcgg ttcatcatct 120 gttgccgtta 180 cttggcgcgt 240 aaaaccagtC 300 aaaaaggaag 360 ttagcgaac 420 ccagtagcgg 480 gttcagaatg 540 *gtcgaaaagg 600 cgtcaggcgg 660 *gatgaagCgC 720 -gtcacccctg 780 t aaagctaaCg 840 g aaatCcgCtg 900 g gct gta 955 t Ala Val gaa gat act caa ccg ctt atc acg Cat ctg atc gag ttg cg- aag cgc 1003 Giu Asp Thr Gin Pro Leu Ile Thr His Leu ie Glu Leu Arg Lys Arg 10 ctg-cta aac tgc aic gtc gca gta ctt ctg att ttt cig gcg tta att 1051 Leu Leu A-sr Cys Ile Val. A-la Val Leu Leu Ile Phe Leu Al1a Leu Ile tat t-c gcc aat gat Tyr Phe Ala Asn Asp att tat cat Ile Tyr His tia gtc gee gca ccg ctg ait aaa 1099 Leu Vai Ala 45 Ala Pro Leu cag atg ceg Gin Met Pro -ttt tit acg Phe Phe Thr ggg gcg aca atg Gly Ala Th~r Met Ile 60 gcg acg gat gig Al1a Thr Asp Val gc; tog cog Ala Ser Pro ate tta too Ile Leu Ser 1147 12.95 cot ate aaa cic pro Ile Lys Leu ttc at; gig tot Phe Met Vai Ser geg cot Ala Pro gtc att ttg tac Val Ile Leu Tyr ca g Gin git tgg gcc tt Vai Trp Ala Phe goc cog gcg ci; Ala Pro Ala Leu tar- Tyr 100 aag cat gag cgt Lys His Giu Ar; Arg 105 ctg gtc gta oct Leu Val Vai Pro ctg Leu 110 ci; gta too ago Leu Val Ser Ser tog Ser 115 1243 1291 1339 1387 ci; cit tic tat Leu Leu Phe Tyr ggt at; gcc tic Gly Met A1a, Phe tat itt gic gia Tyr Phe Val Val tic cci Phe Pro 130 itg gee iii Leu Ala Phe tog aca gat Ser Thr As5P 150 ggt Gi y 135 tic ct; acg oat aog Phe Leu Thz His Thr 140 gcg cog gaa ggg gta cag gtt Ala Pro Glu Gly 145 ato gee ago tat cit ago tti gtc atg gcg cit ttt aig Ile Ala Ser Tyr Leu Ser Phe Val Met Ala Leu Phe Met 155 160 1435 goc tt Ala Phe 165 atg ggc Met Gly 180 go; tagoc itt gaa gig ccg gig go; ait gtg tt; ot; igo tgg 1485 Al1a Phe Giu Val Pro Val Ala Ile Val Leu Leu Cys Trp ato acc ac; ca gaa gat ttg cgt aaa aaa cgg cot tat ate Ile Thr Thr Pro Giu Asp Leu Ar; Lys Lys Arg Pro Tyr Ile 185 190 1533 ci; Leu 195 gtc ggg gca ttc Val Gly Al1a Phe gig gga at; ct; Val Gly Met Leu ac; cog oca gat Thr Pro Pro ASP gt Val 210 1581 tic. tog caa ac; ti; ci; go; ata cc; at; tao igo ci; ttt gaa ati 1629 Phe Ser Gin Thr Leu Leu Ala Ile Pro Met Tyr Cys 21.5 220 ggc gtt ttC tgc tca cgc ttt tat gtc ggt aag cga Gly Vai Phe Cys Ser Arg Phe Tyr Val Gly Lys Arg 230 235 gaa gat aac gag gcc gaa acc gaa aag gcc gag cac Glu Asp Asn Giu Ala Giu Thz Giu Lys Ala Glu His 245 250 taaacacaac cgcccgccag ggcggttgtc atatgggggC aag ttaatttaac cagtagccag tttgcaaaag atcgtgatga tgt cggcgggagt aaaaggtatg ctactgaccg gaacgaacat cca taaaactggc gcggcgctac ccccatttt ggtcgacggc tg gcagtcagtg gtcaCcccgg tctgaagacg ccattattgc gcl tcgtcgctat cggtgagic gggctggatt tcaatcgcaa tt aggagogtgc ctttcaggcg cagctacaaa ttgccgccga at tgcactgcCg ggacgcgcat gagcgatttc tggtattgct tg ttcctggtgc aatactgcac tgctttacCg gttcacgcca gc atagagggct ciatatoggt attaccgggt, gggtttgcga cg tacgtgaact cttaccgttt attccagcgg aaaagctact ga atctgttgcc tcgcgatctt acgccgaaac caacgtcacg ac tgccicacat cctggagcgc atagcgctat ggcgtggtga ac egatgacaga tgccaacgcc agaaccttat ttgaggttgt a 1 cttgcgaaaa ccggtgtttt ttacgct-ctg cttcacttct tf taacatcgaa cgcgttt~cgc catccggttc ggtaaaaatc g gccttccgtg atgatgacgc tatcgccggg atagggggtt t. gggcttgtag atagaaagct gatgaataac gctggaaggc a aa~cgcacaa aatggctgac gccgcgcgtg gcgttgaitg t Leu Phe Giu Ile 225 cgg acg cgc gac Ar-g Thr Arg Asp ga0 1677 1722 act gaa Thr Giu 255 catgtt *ggtcgc Ltgaaagt ;cgtccat :ggcgaac tttccacg tgcagata atccctgg aaatgcac raacgacgc Ltagaaact :gcaacgai ;atzCgCa. ttctgaac tattgagt, ctttcagc caggat~cq *cgatcgca ~agtggtal Asp gatattggcg 1782 cgtgcgtttg 1842 cagcaggcgt 1902 ccccatgaca 1962 cagccggaag 2022 ccgcaggagc 2082 ccaatct.tta 2142 ciggatagic 2202 gccigtgtgg 2262 gggctigagc 2322 gacgcgccgt 2382 ;cccgcgtatc 2442 a tggttagcgg 2502 g atcgctaaat. 2562 a aattaagCag 2622 c cttcaaatgc 2682 ra caacgcCttc 2142 Lg gatgccgcca 2802 q tatcacttcc 2862 ggatcaaatt ccgcgtacca aggtttcet ataatgaCtc attatacact -aatttaac~a ggctacaatg gcagggggaa cgctgaccgc cgccatgccg geaggatgat tgagccgccc gaatatgeCtc tgatgtcgal gatta-ctl9 ttatcgtca' cggcgCgct cgtcgcatt ctgtcggag ttctacgat c-ggagacgt ac-agcgtac Ctcgtctat caacgaacag tttttccag gagcacgctg ttatccgCtt icatcct'tta aaaiacagca gacgccatga ctaaaacgca acgctgcgtg gtgctgtgca gtttccgcct aaagcgtttc Sacgaaacggt ttaacgcgtc ;ggactgacgC g cagttgatat g gattttc-agi g ggcgccgat ,t atgcctttg tggagtgct a tgcgatcat Ta tgcatctat ,c tcaaagtc ataattagga ggtgatcatc aagttgc~cg gttCggggCg agccgiatc-t tcccgatgat aatatcacga tcacgctacc ccggtggac acctttttgg tacgggaagt gcgatctgjtt tacgCggCgc ttcctgtcal taacgcgtgl ;gtaaaaata. ;agtggttag cggcacgai gggcctgct g cagcgcgag a cggcatata *a tcactatac aagagcggt ggtgtcaggc cgtttgcagt caagcatagc ggattagcgt ga acg ccgt-a tttacgcgac tgtggatcct ggcgiigctg cacgccaaaa gggtaaatta tgacaagctc gccttgccac gacctgttg ;tccgcacaa igctgattat cgcgcgtcc a cttggcgcc g cgcggcacg 'a tatcttgaa Lt gagtgatac :g cgcgcatgi cgctgacgga gg aacttaccgc tt acagtaaata cc aaaagccatg c~ tggttlgccag a~ taatgatgcg c ttcctgacgc t catctggaaa t tttgaaaatc c cgcgtggr-ga t ccgcagttta cagaaaatcg ;ccggacgacg a gagcggcaaa g cgctggctgt g ggtgaacgtt g tgactcctgt a aaactgaagt .g tacatgagcg Tc tcgtcttacg kg ctcgtatagg 'tacgtttt 2922 ~gtctttcg 2982 :aggattgc 3042 lcgaagt-ta 3102 gttcacgct 3162 taccaaga 3222 acttgagca 3282 cacggaaat 3342 :taaaggtia 3402 .gggcatggg 3462 ~taaagaaCC 3522 kgcaagjtgc-t 3582 cgtctggcga 3642 :cgcgccgct 3702 acctgggcat 3762 ctcacCgcgg 3822 tcccggictc 3882 tccegatact 3942 ggttaatgct.4002 gagagatgCg 4062 tcacgcaata 4122 tgcctcatat 4182 4200 <210> 16 <211> 166 <212> PRT <213) Salmonella typhimuzium <400> 18 Met 1 Arg Ala Val Glu Asp Thr Gin Pro Leu 5 lie 10 Ala Thr His Leu le Lys Arg Leu Leu Asn Cys Ile Val 25 Ile Val Leu Leu Ile Ala Glu Leu Phe Leu Ala Pro Ala Leu Ile Leu Ile Lys Tyr Phe Ala Asn Tyr His Leu Gln Met Pro Ser Gin Pro Ala Thr Met Thr Asp Val Pro Phe Phe Ile Lys Leu Thr Val Met Val Ser Leu Ser Ala Pro Lys Ile Leu Tyr Gin 90 Leu Trp Ala Ph. Ile Ala Pro -Ala Leu Ser Ser Ser 115 Val Phe Pro Tyr 100 Leu His Glu Arg Arg 105 Giy Val Val Pro Leu Phe Tyr Met Ala Ph. Ala 125 Ala Leu Leu Val 110 Tyr Ph. Val Pro Giu Gly Leu Ala Phe 130 Val Gin Gly 135 Ile Leu Thr His Thr 140 Ser Val Ser Thr 145 Leu Asp 150 Ala Ala Sez Tyr Ph. Val Met Ph. Met Ala <210> 19 <211> 91 <212> PRT <213> Salmonella typhimurium <400> 19 Ph. Giu Val Pro Val Ala Ile Val Leu Leu Cys Trp Met Gly Ile Thr 1. 5 10 Thr Pro Glu Asp Phe Ile Val. Gly Leu Leu Al1a Ile Ser AMg Phe Tyr Leu Arg Lys Lys Ar-g Pro Tyr Ile Leu Val Gly Al1a 25 Met Leu Leu Thr Pro Pro Asp Val Phe Ser Gin Thr 40 Pro Met Tyr Cys Leu Phe Glu Ile Gly Val Phe Cys 55 Val Gly Lys Azg AMr Thr Azg Asp Glu Asp Asn Glu 70 75 Lys Ala Giu His Thr Glu Asp 65 Ala Glu Thr Glu <210> <211> 2601 <212> DNA <213> Neisseria meninigitidis <220> <221> CDS <222> (1572)..(2339) <400> agacaaaatc ctaaaaaaag tgattgaaga caaaaacccg icccacctgg tttacgaagt tcigacacac cacgacctga aggcggaaga tttgtcgggc ttggccgaaa aagccgctcg cactiCoCa cattcaatcC gtctgaccgC aactgtaitt tctgcaaaat cgccgccaaa ggcgaaatgg tttgtttcaa agacatcaac cccaaagtcc atttcgattc gttggcacac aaaatgatgc tgaaagttcc cgaaatcgcc accctgatca acaccggaaa aggcggcgga ggcgggcgaa tgccgactta cgtattggac cacagaatct tgttcagacg gacattccgg cccgctgctc gccgcgcog aaagcggcag caagaggtct gtgttgatgg tggtttcaca gaacttgcgc tgaatttata gcatcggagc cgcaaaccgt cggtteatct aac-atcagc gactggcaga iccacctgca catccaaaga ccatgattat 120 gccgccaagg 180 ttaaaatccg 240 cgttatggac 300 ctatgaagac 360 g.ctgctgatt 420 cct-.-tggga 480 cggcttcaaa 540 tatacacatc 600 atgggcacac catcatgggc ccgtataaac agtttttctc cgttatttca tgacgcactg caatcaacca gatiatcgta ctaatactta ctgattatcg cttaaggata tcgttttgat 660 720 attcgcacc aaaaaactgc gcaacgt.Cgg caaagacctc ggcggtgcgg ttcatgactt 78~0 caaacagggg ctgaacgaag gtacagacgg acacaaaaaa ttttgtcggC caccgccgga tgaca cgcaa tgctcaggtt catttogac cggtgtogat ttccgacgtt gacgaacaca attatcgCc cggctcatcg atcgaactgg ogagacagc ggtcigaagc gaaaacggca atgccgtCcg aagcgtaatt tgattgtcct gcaggctgca ,aagaactaag tcaaagaaac cttgggaaaa aacgttccta caaagaagcc tatgtttgat cggccccgaa acgetttgtc gaaggcaaag cggtacggat actgcccgaa cgatgcggca cgcttccgc aaccgaccaa acagaccgic ttcgctgcgt caaaaagacg ttcggtttgg cgcctgcccg ggcagcgtca caggaatttg atggagggta cagcgcacgc aacaccctat gaaacccttg gaccgtgcat *gaagtcagct *aaacaggcaa atgtaatcga gcgagctggt. aggccgcccg aacaggaatt aagctgcc atctgcaega ctgoigattt tagacggcat gggacagcgg ggcgggaata atatcgatac taagccgcaa 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 gcaaaccggc agiacageog aacccgcgga cctgactgct, cgctgttgaa acgcgatttg agggcaatcc gic gag ca Val Glu H!. ggt atc tti Glv Ile Le ictgccgcCg caccogiogi acccctgttc cgcataccac cgtcctaaat cccgcgccaa g gtg tcc gaa aca caa Vai Ser Glu Thr Gin 1 5 acctaaattg cgcgtccgta aatcataaag 1560 aac gaa caa tcc gtc caa cog ctt. 1610 Asn Glu Gin Pro Val. GIn Pro Leu cgc cgc ctg atg tgg acg gtt gic 1658 A.rg Axg Leu Met Trp Thr Val. Val. cta atg cog itt goc caa caa ctc 1706 Leu Met Pro Phe Ala Gin Gin Leu 40 t ctc atc gag s Leu Ile Giu ctg cgc Leu Arg 20 ttc ggc Phe Gly a gic tgc Val. Cys tat Tyr act tit aic gcc Thr Phe Ile Al1a s0 ttt Phe 35 gac Asp 1754 cog ctg atg gca aac ctg ccc aaa gao acc Pro Leu Met Ala Asn Leu Pro Lys Asp Thr 55 agC atg att gcc ace gat gtc atc gca cca tii tic gtg ccg gtc aaa 1802 Ser Met Ile A.la Thr Asp Val Ile A-1a Pro Phe Phe Val Pro Val Lvs gtt acc cig atg Val Thr Leu Met so gcg gca tt Ala Ala Phe tta ati tcg Leu Ile Scr 85 cig ccg cat Leu Pro His acg cic tac Thz Leu Tyr 1850 caa atc Gin Ile t gg Trp, gca tic gic Ala Phe Val gcc Al. a 100 ccc gca ctc tac Pro Ala Leu Tyr aac gaa aaa cgc Asn Giu Lys Arg ati acg ccg cic Ile Thr Pro Leu ctc tcc age gtc Leu Ser Ser Val cig ttt tic atc Leu Phe Phe le 1898 1946 1994 aig gca ttt gcc Met Ala Phe Ala tac Tyr 130 tit ttg gtt tic Ph. Leu Val Phe ccc Pro 135 gic ait tic aaa Val Ile Phe Lys tic ci: Phe Leu 140 gcc agC gt Ala Ser Val a ce Thr 145 cct gtC ggt gtc Pro Val Gly Val aat Asn 150 aig gcg aca gac Met Ala Thr Asp ate gac aaa. Ile Asp Lys 155 aca acg tti Thr Thr Phe 2042 tac ctc Tyr Leu gaa gtc Giu Val 175 tee Ser 160 tic ate ttg ggg Phe Ile Leu Gly atg Met 165 ttt gic gca tic Phe Val Ala Phe ggt Gi y 170 CCC ati gqic gt Pro Ile Val Val ate Ile 180 ctg tta. ace aaa. Leu Leu Thr Lys at Ile 185 ait Ile ggi gig gta aca Gly Val Val Thr acec Thr 190 gaa cag cic aaa Glu Gin Leu Lys cgc Arg 195 gcc cgC ccc tat Ala Arg Pro Tyr gig Val 200 gic ggc gcq Val Gly Al1a 2090 2138 2186 2234 2282 gic ati gcc gcc Val Ile Ala Ala atc Ile 210 atc acg ccg cc Ile Thr Pro Pro gig ati tca caa Val Ile Ser Gin ace ctg Thr Leu 220 tic gga Phe Giy cii gcc at Leu Ala Ile ccg Pro 225 cig ati ctc Leu Ile Leu ita tac Leu Tyr .230 gaa gca ggi ati Giu Ala Gly Ile tgg T rp 235 cgc tt Arg Phe tic Phe 240 acg cca cgt ica Thr Pro Arg Se: gaa. Glu 245 cag gat Gin Asp ggc gac Gly Asp ata Ile 250 cag ccg cci Gin Pro Pro 2330 2379 gca aca acC igacactaig ccgtcCgaac ctccgcctca taccgccaca Ala Th~r Thr 255 gattaaggaa tacctttgaa taccctctat ttaggttcaa acagcCgcg atcctgacac agttgggcta tcaggtcgtc aagctlgcctg ccaacatcga agacagaaCg aagaccctgc ccgttacgtt caaaggatgg cagaagaaaa gccCtgaccc tcttttgcga aaccaacggc acaatgc~cc at cagaatggaa 2439 cgaaacggtc 2499 aaaccgaacc 2559 2601 <210> 21 <211> 256 <212> PRT <213> Neisseria <400> 21 Val Ser Giu Thr meningitidis Gin Asn Giu Gin Pro Val Gln Pro Lou Vai Glu His Lou Ile Giu Leu Val cvs Phe Phe Arg Arg Arg Lou Met Trp Thr Val Val Gly Ile Lau Tyr Thr Phe Ser Met Ile Giy Leu Met Phe Ala Gin Gin Ile Ala Asp Lou Thr Pro Leu Met Al1 a Pro Lou Pro Lys Asp Vai Ala Thr Met Ala Ala Phe Asp Vai Ile Ala Phe Lou Val Al1a Pro Ala 70 Ile Phe Phe Vai Pro 75 Thr Lys Val Thr Lou Ser Lou Pro His 90 Lou Tyr Gin Ile Trp, Ala Lou Tyr 100 105 Giu Lys Ar-g Phe Ile Giy 110 Met Ala Phe Pro Lou Vai Lou 115 Ala Tyr Phe Lou 130 Ser Ser Vai Vai Phe Pro 135 120 Val Ile Phe Lys Phe Lou Ala Ser Vai 140 Thr pro Val Gly Val Asn 145 '150 Met Ala Thr Asp Ile Asp Lys Tyr Lou Ser 155 160 Phe Ile Leu Gly Met 165 Phe Val Ala Phe Gly Thr Thr Phe GlU Val. Pro Ile Val Val Leu Lys Arg 195 Ile 180 Leu Leu Thr Lys Ile 185 Gly Val Val Thr Thr Glu Gin 190 Val Ile Ala Ala Arg Pro Tyr Ile Val Gly ALla Ala Ile 210 Ile Thr Pro Pro Asp 215 Val. Ile Ser Gin Leu Leu Ala Ile Leu le Leu Leu Tyr 230 Giu Ala Gly Ile Trp 235 Phe Giy Arg Phe Phe 240 Thr Pro Arg Ser Gi u 245 Gin Asp Gly Asp .le Gin Pro Pro Ala Th: Thr 250 255 <210> <211.> <212> <213> 22 4604 DrNk Escherichla coi. <220> <223.> Cns <222> (2982).. (4082) <220> <221> CDS <222> (1534) .(2637) <220> <221> <222> <220> <221> <222> <400> ggcta CDs ('749) (1531) CDs (746) 22 gtt gat gat aat ttg aaa ggt caa ggt gca gga aaa aat ttt tta Vai Asp Asp Asn Leu Lys Gly Gin Gly Ala Giy Lys Asn Phe Leu 1 5 10 tCg ctg ata aag tac agc gag aca gat tat aca. att tat tgt gac caa 98 Leu Ile Lys Tyr Ser Giu Thr A-sp Tyr Thr Ile Tyr Cys Asp Gin tat gca Tyr Ala gat gat att tgg Asp A-sp Ile Trp tta gaa aac aaa ata ttt gaa tta gta Leu Giu Asn Lys Ile Phe Giu Leu Val. 40 aag Lys 146 aat gaa ait aaa ttg Asn Giu Iie-Lys Leu aat gia tea Asn Val Ser gat gcg cct tcg Asp Al1a Pro Ser git tat get Val. Tyr Ala gat ggc Asp Gly tat gct Tyr Ala tat atg gat Tyr Met Asp ggt gag ggt aca Gly Giu Gly Thr gat ttt tct ggg Asp Phe Ser Gly tct aac aat cat Ser Asn Asfl His get gat caa tta aag Ala Asp Gin Leu Lys tgt tct att atg ttc Cys Se Ile Met Phe 105 Phe Leu Phe Phe aai Asn 242 290 338 ggt gga tac caa Gly Gly Tyr Gin gga Gly 100 aat cgt gca atg Asri Arg Al1a Met ace aaa Thr Lys 110 ttt ctt ctg Phe Leu Leu aca tta gct Thr Leu Ala 130 tat cga gga ttt Tyr Arg Gly Phe gta Val 120 tat eta cat gac Tyr Leu His Asp gat ate aca Asp Ile Thr 125 ccg aaa tac Pro Lys Tyr 386 434 gca tac gct ctt Ala Tyr Ala Leu aaa gtt tat ttt Lys Val Tyr Phe ctc Leu 140 ctt atg Leu Met 145 tia tat aga cag Leu Tyr Arg Gin acg aat gcg gia Thr Asn Ala Val ggt ate aaa aca Gly Ile Lys Thr 482 530 ttc ?he 160 cgc aat gga ttg A.rg Asn Gly Leu tct aaa ttt aaa Ser Lys Phe Lys tca Ser 170 cca gta aac tat Pro Va]. Asn Tyr ctt Leti 175 tta tea cga aaa Leu Ser Arg Lys tat cag gta aaa aaa tct ttt ttt gaa Tyr Gin Val Lys Lys 5cr Phe Phe Glu 185 tgt aac Cys Asn 190 agc tct ate Ser Se: Ile tca gag acg aat Ser Giu Thr Asn aaa Lys 200 aaa git ttt ttg Lys Val Phe Leu gat ttt att Asp Phe Ile 205 aag tta tgg tea ttt tgt gaa tca aat aat aaa ttt aca gat ttt ttt Phe Cys Giu Se~r Asn Asn Lys Prie Thr Asp Phe Phe Lys Leu Trp 210 215 220 ega A.rg tic Phe 240 ggt Gi y 225 ggg ttt aga Gly Phe Arg tia aat Leu Asfl 230 aae agi aga act Asn Sex Arg Thr aaa tta tta tta aaa Lys Leu Leu Leu Lys 235 tia ata egg aga Leu Ile Arg A-rg aaa Lys 245 ttt agc ga atg att Phe Ser Met Ile tea at'a cit aca act Set le Leu Thr- Pro 250 act Th~r 255 tit aai cgg caa Phe Asfl Arg Gin caa act gat aaa Gin Thr A-sp Lys 275 act ita ica agg Thr Leu Set Azrg eta Leu 265 tic aai tct eti Phe Asn Set Leu ita Lau gat itt gag tgg Asp Phe Giu Trp ata ati gat gat Ile Ile Asp A-Sp ggt agt Gly Set 285 ata gat gea Ile Asp Ala ttt gac tig Phe Asp Leu 305 a ca Thr 290 gag gta cit gta Ala Val Leu Val gaa Glu 295 gat ttt aga aaa Asp Phe Arg Lys aaa tgt gat Lys Cys Asp 300 ccc atg get Pro Met Ala att tat tgc tat Ile Tyr Cys Tyr gaa aat aat ggt Glu Asn Asn Gly aag Lys 315 ita aae Leu Asfl 320 get ggt git aaa Ala Gly Val Lys igi aga ggc gat cys Arg Giy Asp tat Tyr 330 ate tii ait gt Ile Phe Ile Vai gac Asp 335 tea Set agt gat gat ga Ser Asp Asp Al1a ata eat gat tge Ile His Asp Cys 355 eta Leu 340 act CCC gat gee Thr Pro Asp, Ala ata Ile 345 aaa ita ati aaa Lys Leu Ile Lys gaa Giu 350 1009 1057

1105- tia tat gag aag Leu Set Giu Lys agi ttc age gga. Set Phe Set Giy gte ggt Val Giy 365 iii aga aaa Phe Azrg Lys aat tat tea Asn Set Set 385 gea Ala 370 tat ata aaa ggg Tyr Ile Lys Gly ggg GI y 375 att ati ggt aat Ile Ile Gly Asn gat tia aat Asp .Leu Asn 380 ait age aat Ile Set Asn 1153 1201 gaa eat ata tae Giu His Ile Tyr tia aat geg Leu Asn Ala act gag Thr Giu 395 tia ata aat ggt gat gtt gca tat tgt tit aaa aaa gaa agi tig gta 1249 Leu Ile As Gly Asp Val Ala Tyr Cys Phe Lys Lys Glu Ser Leu Val 400 405 410 aaa Lys 415 aat cca tic ccc Asn Pro Phe Pro cgt Arg 420 ata gaa gat gaa Ile Giu Asp Glu aaa Lys 425 itt git cca gaa Phe Val Pro Glu tta Leu 430 tat ait igg aat Tyr Ile Trp Asn aaa ata act gac aag gcg aag ait cga ttt Lys Ile Arg Phe Lys 435 Ile Thr Asp Lys aac ata Asn lle 445 tat aaa Ser Lys 1297 1345 1393 agc aaa gtt Ser Lys Val aat tic cat Asn Phe His 465 ata Ile 450 tat ctt tgt gag tat Tyr Leu Cys Glu-Tyr 455 ctt gat gat ggi Leu Asp AsP Giy cti Leu 460 aac cag ctt aaa Asn Gin Leu Lys aaa tac Lys Tyr 470 cca aag ggg Pro Lys Giy aag ait tat Lys Ile Tyr 1441 tac aaa Tyr Lys 480 gat caa aga aaa Asp Gin Arg Lys cga Arg 485 gag aaa act tat Glu Lys Thr Tyr ata le 490 aaa aaa aca aag Lys Lys Thr Lys atg Met 495 aaa Lys 510 cta att aga tat Leu Ile Arg Tyr ata cia ttt gic Ile Leu Phe Val tig Lau 500 att Ile 515 caa tgt tgt tat Gin Cys Cys Tyr aca ggt tia ggc Thr Gly Leu Gly tat Tyr 505 ct Leu 520 gag aaa ata aa atg Glu Lys Ile Met gga ggt gct gag aa Gly Giy Ala Giu Ly 52 1489 1536 1584 1632 cag gt tgt ctt Gin Val Cys Leu tta Leu 530 get gat aaa ita Ala Asp Lys Leu ita agc ggg cac Leu Ser Giy His cat gta His Vai 540 aag at ati Lys Ile Ile gaa aat aat Giu Asn Asn 560 ctt gga cat atg Leu Giy His Met tct Ser 550 aat aat aaa gic A-sn Asn Lys Val ttt cci agc Phe Pro Se: 555 aac att tct Asn Ile Se: 1680 1728 gtt aai gtc att Val Asn Val Ile gta aat atg tca Vai Asn Met Se: aaa Lys 570 gga gtt Gly Val 575 ata aaa ggt tgi Ile Lys Gly Cys aga ait aga gat Arg Ile Arg Asp gtt Val 585 ata get aat tic Ile Ala Asn Phe 1776 aaa cca gac att gia cac agt cat aig ttt cat gca aaC att atc act 1824 Lys pro Asp Ile 590 aga ttg tot gta Arg Leu Ser Val Val. His Ser His Met Phe His Al1a Asn Ile Ile Thr 595 gga aic aaa aac Gly Ile Lys Asn 600 cct ggt ati ata Pro Gly Ile Ile aga Arg 615 tca act Ser Thr 620 1872 gca cat aat Ala His Asn ata acc gat Ile Thr Asp 640 aat gaa ggt ggg Asn Giu Gly Giy tat Tyr 630 ttc aga atg ctc Phe Arg Met Leu aca tat aga Thr Tyr Arg 635 aaa gaa gca Lys Giu Al1a 1920 1968 tgt tta agt gat Cys Leu Ser Asp tgt tgt Cys Cys 645 aca aat gtt Thr Asn Val agc Ser 650 gtg gat Val) Asp 655 gag ttt tta cgg Glu Ph. Leu Arg aaa goc ttt aat Lys Ala Ph. Asn ccc Pro 665 got aaa gca att A1a Lys Ala Ile act Thr 670 atg tat aat ggg Met Tyr Asn Gly gat acc aat aaa Asp Th~r Asn Lys ttt Phe 680 aa ttt gat tta Lys Ph. Asp Leu 2016 2064 2112 gca agg agg ga Ala Arg Arg Glu cga gac ggt att Arg Asp Gly Ile sat Asn 695 ata aaa sat gat Ile Lys Asn Asp gat ata Asp Ile 700 tta tia ott Leu Leu Leu tta ttg aat Leu Leu Asn 720 got Ala 705 gca ggt cgt ita Ala Gly Axrg Leu acg Thr 710 tta gct asa gat Leu Al1a Lys Asp tat cct aat Tyr Pro Asn 715 ctt stt att Lau Ile Ile 2160 2208 gas atg act cig Ala met Thx Leu ott Lau 725 cot gaa ca0 ttt Pro Glu His Ph. aa Lys 730 att ggt Ile Gly 735 gat ggt gaa ttg cgt, Asp Giy Glu Leu Arg 740 gac gaa att aat Asp Giu Ile Asn atg Met 745 ott ata ass aaa Leu Ile Lys Lys ttg Leu 750 caa tta tot aat Gin Leu Ser Asn gtg too ttg ttg Val Ser Lau Leu gtt aaa aaa aat Vai Lys Lys Asn att Ile 765 2256 2304 2352 got coo tat ttt Ala Pro Tyr Phe gca tgjt gat att Ala Cys Asp Ile ttt Ph. 775 gtt cic tot tot Val Leu Ser Se: ogt tgg Arg Trp 780 gsa *gga ttt gga tta gtc gtg gos gas gct atg tcs tgt gag cga att 2400 Glu Gly Phe Gly Leu Val Val Ala Giu Ala Met Ser Cys Giu Arg Ile git git ggc Val. Val Gly 800 gat ttt ctt Asp Phe Leu acg Thr gat ica ggg Asp Ser Gly gia aga gaa gt Val. Arg Giu Val. gac gat Asp Asp gta ccc ata Val Pro Ile 815 aaa Lys tct Ser 820 cag Gin ica aca caa Ser Thr Gin ctt Leu 825 at Ile agc aaa at Sexr Lys Ile 2448 2496 2544 2592 ga a Giu 830 cgi A~rg ttg tct ttg Leu Ser Leu ata cgi gat Ile Arg Asp cac His 840 gat Asp ggt itt cgg Giy Phe Arg aat As n 845 ca g Gin gag cgt att GiU Arg Ile tta Leu 850 tat Tyr aat tic tca Asn Phe Sex act att ati Thr le Ile atg Met 860 igg caa gaa ctc Trp GIn Giu Leu gga act ata att Giy Thr Ile Ile tagattiata tgtatttcaa aiaaatatat ctgttitgag ttaattaiii atattaatta tttggaacgt, aaatacca tc t gacgttttt aatgaagagt ataataaatc tgagtggtac gicttigt atagctaacg aatgcgccga tttgagaig aagatiiaat gtttggtaaa 87 0 tgaaiit atgattc aacgati tttatg giiaait cggtaa 1 tca aaa cat gaa agg 2637 Ser Lys His Giu Arg 875 .aat tcaaictcaa ttgagaittt 2697 ;gta tttattttaa gatgctttct 2757 :ggg ctgggaacag agaagtaaaa 2817 ;ata ttaaaaattg atccagtgaa 2877 iaat gaiaatcti tctgacactc 2937 acta itat atg aca gct aga 2993 Met Thr Al1a Arg 880 cca ctc tia agt ggc git 3041 Pro Leu Leu Ser Giy Val 895 tia tat act gat tat gat 3089 Leu Tyr Thr Asp Tyr Asp 910 cia aca aaa gca ttg cig 3137 Leu Thr Lys Ala Leu Leu 925 aca act aaa git tig cac tta Thr Thz Lys Val Leu His Leu 885 caa agg gta aca tta aac gaa Gin Arg Vai Thr Leu Asn Giu 900 tat aca cta git tgc ica aaa Tyr Thr Leu Val Cys Se: Lys 915 caa tta cic Gin Leu Leu 890 att agi gcg Ile Ser Ala 905 aaa ggt cca Lys Gly Pro 920 42 gaa tat Glu Tyr 930 gat gtc gat tgt Asp Val Asp Cys cat His 935 tgt aic ccc gaa Cys Ile Pro Glu ctt Leu 940 acg aga gaa att Thr A-rg Giu Ile acc Thr 945 aaa Lys gta aag aat gat Vai Lys Asn Asp aaa gaa aaa ttt Lys Giu Lys Phe 965 aaa gca ttg ttc Lys Aa Leu Phe ctt tat aag ttc Leu Tyr Lys Phe 3185 3233 3281 gac att gtg cat Asp Ile Val His cat tct tca aaa His Sex Ser Lys aca ggt Thr Gly 975 att ttg ggg Ile Leu Gly cac act gta His Thr Val 995 cga Arg 980 gtt gct gcc aaa Val Ala Ala Lys tta Leu 985 gca cgt gtt gga Ala Arg Val Gly aag gtg atc Lys Val Ile 990 aaa aaa agt Lys Lys Ser 3329 3377 cat ggt ttt tc ttt His Giy Phe Se: Phe 1000 cca gcc gca Pro M-a Ala tct agi Se: Ser 1005 tat tac Tyr Tyr 1010 aag tta Lys Leu 1025 ctt tat ttt ttc atg Leu Tyr Phe Phe Met 1015 gaa tgg ata gca aag Glu Trp Ile Ala Lys 1020 ttc ttt acg gat Phe Phe Thr Asp 3425 3473 atc gtc ttg aat Ile Val Lau Asn 1030 gta gat gat gaa tat Val Asp Asp Giu Tyr 1035 ata gca ata aac aaa Ile Ala Ile Asn Lys 1040 tta aaa ttc aag cgg Leu Lys Phe Lys Azg 1045 gat aaa gtt ttt tta att cct aat gga gta gac Asp Lys Val Phe Leu Ile Pro Asn Giy Val Asp 1050 1055 3521 act gat aag Thr Asp Lys aat cta gta Asn Lau Val 1075 ttt Phe 1060 tct cct tta gaa aat Se: Pro Leu Giu Asn 1065 aaa att tat agt Lys Ile Tyr Sex agc acc ttg Se: Thr Leu 1070 cat gag aca Pro Giu Thr 3569 3617 atg git ggt Met Val Gly aga tta Arg Leu 1080 tcc aag caa aaa Se: Lys Gin Lys gat Asp 1085 tta ttg ctt gct gtt Leu Leu Leu Aa Vai 1090 gaa aaa Glu Lys 1095 ctg ctg aat gaa aat Leu Leu Asn Glu Asn 1100 gtt aat gtt aag Val Asn Val Lys 3665 ctg aca ctt gta gga gat ggi gaa cta aaa gaa cag tta gaa agc agg Leu Thr Leu Val Gly Asp Gly Giu Leu Lys Giu Gin Leu Glu Ser Arg 3713 1105. 1110 1115 1120 ttc aaa cgg caa gat Phe Lys Axrg Gin Asp 1125 att git aat att tta Ile Val Asn Ile Leu 1140 gga cgt ata att tt Gly Arg Ile Ile Phe 1130 aaa gtt aat gat ct Lys Val Asn Asp Leu cat gga tgg tea gat aac His Gly Trp Ser Asp A-sn 1135 ttt ata tia cct ict ctt Phe Ile Leu Pro Ser Leu 1150 gca ttg age tgt gga ct Ai1a Leu Ser Cys Giy Leu tgg gag ggt Trp Giu Gly 1155 aig Met c ca Pro 1145 tta gca ati tta Leu Ala Ile Leu 1160 gaa Giu cca igt Pro Cys 1170 ggc tat Gly Tyr 1185 caa aaa Gin Lys ata Ile gtc act eat Val Thr As~n att cca ggt Ile Pro Giy 1175 aat aat agc Asn Asn Se: 1180 1165 ita Leu eta gee get Ile Giu Asp 3761 3809 3857 3905 3953 4001 4049 aat ggi tgt Asn Gly Cye tig Lau 1190 tat Tyr ttt Phe gt Val ate atg Ile Met tea Sez 12 05 cga Arg gae att age gat Giu Ile Arg Asp 1195 ggt, aag eca gaa Gly Lye Pro Giu 1210 ati ctg aaa aat Ile Lau Lye Asn 1225 cta tat gat eat Leu Tyr Asp Asn tgt Cys cag tie tt Gin Leu Letu tet. Ser 1200 tct ace eat gea Se: Thr Asn Ala 1220 aga eat eat aag Arg Asn Asn Lys tea tt Se: Phe ci; ait gca Leu Ile Ala tat gga tta Tyr Gly Leu 123C taaatgaaac *cag eaa Gin Gin 1215 gtt aa iVal. Lys gte age Cag Val Arg Gin egaagtta 4102 1.235 1240 aaaaagaa cgtaacatet aaacaatgtc egceeacat eggaegaagt egtgttga ggcacqgatg gatgggtggg ggtttttcae gcettecatt aaagcaacag cgaaagccgi tatigcegaa atctcttgaa ctgctattge taatacettc agtgaaaata eaagccgec etcggcgtcg ggttataecg aiceaggca acgcetcgtc ttcctgeaaa ticeggace 44 aatacagt aaccccgcgg tcggtatggc tetetatti agaatggt geaicctqjti ceatatcteg ecetegteg ttitttatt tgeecaccce agtgatggga caaccgttce tcattactet aatgggttaa ataaaggcga taaccgcgag caaigattaa igacaggagt cgcaacctcg cgtgaaaaga acggtgaeeg agcaggtgca tatcateett Ctttctgcac 4162 4222 4282 4342 4402 4462 4522 4582 4604 aaggCtttac ttcatcggia cc <210> 23 <211> 247 <212> PRT <213> Escherichia coli <400> 23 Val Asp Asp 1 Leu Ile Lys Asp Ile Trp Glu Ile Lys Asn Leu Lys Giy Gin Gly Ala Gly Lys Asn Phe Leu Ser Tyr Leu Ser Glu Glu Asn Thr Asp Tyr 25 Lys Ile Phe Thr Ile Tyr Cys Glu Leu Vai Lys Val Asp Gin Asp Tyr Ala Asn Tyr Ala Asp Leu Asn Val Ser Gly Ala Pro Ser Leu Asp Giy Ser Ala Tyr Met Glu Gly Thr Ile Phe Phe Ser Gly Asn Asn His Ala Cys Gin Leu Lys Asp 90 Asn Leu Phe Phe Asn Gly Gly Tyr Gln Leu Leu Asn 115 Leu Ala Ala Giy 100 Tyr Ser Ile Met Phe 105 Tyr Arg Ala Met Arg Giy Phe Leu His Asp Asp 125 Tvr Phe Leu Pro Thr Lys Phe 110 Ile Thr Thr Lys Tyr Leu Tyr Ala Leu 130 Met Leu Giy 135 Thr Val 140 Giy Tyr Arg Gln 145 Arg His 150 Ser Asn Ala Val Th: 155 Pro Ile Lys Thr Phe 160 Asn Giy Leu Thr 165 Tyr Lys Phe Lys Ser 170 Ser Val Asn Tyr Leu Leu 175 Ser Arg Lys Ser le Leu 195 His 180 Ser Gin Val Lys Lys 185 Lys Phe Phe Glu Cys Asn Ser 190 Phe Ile Se: Giu Thr Asn Val Phe Leu Asp 205 Phe Cys Glu 210 Gly Gly Phe 225 Ser Asn Asn Arg Leu Asn 230 Lys 215 Phe Thr Asp Phe Phe Lys Leu Trp Arg 220 Lys Leu Leu Leu Lys Phe 235 240 Asn Se: Arg Thr Leu Ile Arg Arg Lys Phe Ser 245 <210> 24 <211> 261 <212> PRT <213> Escherichia coi4 <400> 24 Met Ile Ser Ile 1 Arg Leu Phe Asn le Ile Ile Asp Leu Thr Pro Thr Phe Asn Arg Gln His Thx Leu Ser Ser Leu Ile Leu Gin 25 Thr Asp Lys Asp Phe Giu Trp Leu Val Giu Asp Gly Se: Ile 40 Asp Ala Thr Ala Val Asp Phe A.rg Lys Lys Cys Asp 55 Phe Asp Leu Ile Tyr Cys Tyr Gin Glu Val Lys Ala Cys Arg Asn Gly Asn Gly Lys Pro Asp Tyr Ile Phe Met 70 Ala Leu Asn Ala Gly le Val Asp Ser Asp Ala Leu Thr Pro Asp Ala Ile Lys Glu Ser Phe 115 Leu 100 Ile Lys Giu Ser Ile 105 His Asp Cys Leu Ser Giu Lys 110 Lys Giy Gly Ser Giy Val Gly Arg Lys Ala Tyr Ile 125 lie Ile 130 Gly Asn Asp Leu Asn Ser Ser Giu His Ile Tyr Tyr Leu 140 Asn Ala Thr Giu Ile 145 Ser 150 Asn Lou le Asn Gly 155 Asp Vai Ala Tyr Cys 160 Phe.Lys Lys Giu Ser Lou Val Lys Asn Pro Phe Pro Arg Ile Giu Asp Glu Lys Phe Val 180 Ala Lys Ile Arg 195 Pro Giu Leu Tyr Ile 185 Trp Asn Lys Ile Thr Asp Lys 190 cys Glu Tyr Phe Asn Ile Ser 200 Lys Val Ile Tyr Leu 205 Leu Asp 210 Asp Gly Leu Ser Lys 215 Asn Phe His Asn Gin 220 Leu Lys Lys Tyr Pro 225 Thr Lys Gly Phe Lys Tyr Ile Lys Lys 245 Ile 230 Tyr Tyr Lys Asp Gin 235 Arg Lys Arg Glu Lys 240 Thr Lys Met Leu Ile 250 AIrg Tyr Leu Gin Cys Cys 255 Tyr Tyr Glu Lys Ile 260 <210> <211> 368 <212> PRT <213> Escherchia coli <400> Met Lys Ile Leu Phe 1 5 Val Ile Thr Gly Leu 10 Gly Leu Gly Gly Aa Glu Lys Gin Val Val Lys Ile Cys Leu Leu Ala Asp Lys 25 Leu Se: Leu Ser Gly His His Val Phe Pro Ile Ser Leu Gly His Met Ser Asn Asn Ser Glu Asn Asn Val Asn Ile Asn Val Asn Met Ser Lys Asn Ile Ser Gly Val Ile Lys Giy 70 Cys Val Arg Ile Arg 75 Asp Val Ile Ala Asn Phe Lys Pro Asp Val His Se:r His Met Phe His Ala Asn Ile Ile Thr Arg Leu Val Ile Gly Ile Lys 105 Asn Arg Pro Giy Ile Ile Ser 110 Thr Ala His Asn Lys Asn 115 Glu Gly Gly 120 Tyr Phe Arg Met Lau Thr Tyr 125 Arg lie Thr 130 Asp Cys Leu Ser Asp 135 Cys Cys Thr Asn Val Ser Lys Giu 140 Ala 145 Val Asp Glu Phe Leu 150 Arg Ile Lys Ala Phe 155 Asn Pro Ala Lys Ile Thr Met Tyr Asn 165 Gly Ile Asp Th: Asn 170 Lys Phe Lys Phe Asp Leu 175 Leu Ala Arg Ile Leu Leu 195 Glu Ile Arg Asp Ile Asn Ile Lys Asn Asp Asp Asp Tyr Pro Leu Ala Ala Gly Lau Thr Leu Ala Lys 205 Asn Leu 210 Leu Asn Ala Met Thr 215 Leu Leu Pro Glu His 220 Phe Lys Leu Ile Ile Gly Asp Gly Leu Arg Asp Glu Ile 235 Asn Met Leu Ile Lys Leu Gin Lau 5cr Asn Arg Val Ser 245 Lou 250 Leu Giy Val Lys Lys Asn 255 lie Ala Pro Trp Glu Gly 275 Phe Ser Ala Cys Asp 265 Ile Phe Val Leu Ser Se: Arg 270 Cys Giu Arg Phe Gy Lau Val Ala Glu Ala Met Ser 285 Ile Val 290 Val Gly Thr Asp Ser 295 Gly Gly Val Arg Val Ile Gly Asp Asp 305 Asp Phe Leu Vai Pro 310 Ile Ser Asp Ser Gin Lou Ala Ser Lys 320 Ile Glu Lys Lou Ser 325 Lou Se: Gin Ile Asp His Ile Gly Phe Arg 335 Asn Arg Glu Gin Trp Gin 355 Ar; 340 Ile Lou Lys Asn Phe 345 Ser Ile Asp Thr Ile Ile Met 350 Lys His Giu Ar; 365 Glu LOu Tyr Gly Thr 360 Ie Ile Cys Ser <210> 26 <211> 367 <212> PRT <213> Escherichia coli <400> 26 Met Thr Ala Arg Thr Thr Lys Val Leu His Leu Gin Leu Leu Pro Leu Leu Ser Gly Thr Asp Tyr Val Gin Arg Val Thr Asn Giu Ile Ser Ala Leu Tyr Pro Leu Th: Asp Tyr Thr Leu Vai Cys Ser Lys Lys Lys Ala Leu Leu Glu Tyr Asp 55 Val Asp Cys His Cys Ile Pro Glu Leu Thr Arg Glu Ile Thr Tyr Lys Phe Ile Lys Val 70 Lys Asn Asp Phe Lys Ala Leu Phe Lys Lys Glu Lys Phe Asp 90 Ile Val His Thr His Ser Ser Lys Thr Giy Lys Val 115 Gly 100 Ile Leu Gly Arg Val 105 Ala Ala Lys Leu Ala Arg Val 110 Ala Ala Ser Ile His Thr Val Gly Phe Ser Phe Lys 130 Lys Ser Tyr Tyr Leu 135 Tyr Phe Phe Met Glu 140 Trp lie Ala Lys Phe Thr Asp Lys Ile Va Leu Asn Val 155 Asp Asp Glu Tyr Ala Ile Asn Lys Leu 165 Lys Phe Lys Arg Lys Val Phe Leu Ile Pro 175 Asn Gly Val Ser Ser Thr 195 Asp Pro Glu 210 Asp 180 Thr Asp Lys Phe Ser 185 Pro Leu Glu Asn Lys.I1e Tyr 190 Lys Gin Lys Leu Asn Leu Val Met 200 Val Gly Arg Leu Ser 205 Thr Leu Leu Leu 215 Ala Va] Glu Lys Leu 220 Leu Asn Giu Asn Val 225 Leu Asr Val. Lys Leu Giu Ser Arg Phe 245 Thr 230 Leu Val. Giy Asp Gi y 235 Giu Leu Lys G2.u Lys Azg Gin Asp Gi y 250 Azg Ile Ile Phe His Gly 255 Trp Ser Asp Leu Pro Ser 275 Asn 260 Ile Val. Asn Ile Leu 265 Lys Val. Asn Asp Leu Phe Ile 270 Glu Aia Leu Leu Trp Giu Gly Pro Leu Ala Ile Leu 285 Ser Cys 290 Giy Leu Pro Cys Ile 295 Val. Thr Asn Ile Gly Asn Asn Ile Giu Asp Gly Tyr 310 Asn Giy Cys Leu Giu Ile Arg Asp Gin Leu Leu Se: Gin 325 Lys Ile Met 5cr Tyr 330 Val. Gly Lys Pro Glu Leu 335 Ile Ala Gin Gly Leu Va]. 355 Ser Thr Asn Ala Se: Phe Ile Leu Lys Asn Tyr 350 Lys Arg Asn Asri Val Ar; Gin Leu Tyr Asp Asn 365 <210> <21i> <212> <213> <220> <221> <222> <220> <221> <222> 27 272 Escherichia coli CDs (319) (1269) CDs .(215) <400> 27 cc ggg aag cac tcg gcg ctg att gtt gca cat cgt ctg acc acc gcg Giy Lys His Sex Ala Leu Ile Va]. Ala His Arg Leu Thr Thr Ala 1 5 10 eaa cge tgc gat Gin Arg Cys Asp tac gga ace cac Tyr Gly Thr His att gee gtt att gat aag ggg lie Ala Val Ile Asp Lys Giy ita ctt gcg gaa Leu Leu Ala Glu gaa cag ctg Glu Gin Leu tia tct gcg ggc ggc Leu Ser Ala Gly Gly 40 agt act get etc cat Ser Thr Ala Leu His 55 cte tat Leu Tyr ace cge Thr Azg tta tgg cat Leu Trp His gac age gte age Asp Se~r Val Sex ege Azrg eag cac aac Gin His Asn atg aag Met Lys gag gaa ace ccg gga Giu Giu Thr Pro Gly tag- ttactggaca cgtaatgtat taaaaacaca 245 gteagaagCg geggtaccgt gaa tagcege tttaattatt tataetgaea tccttaattt 305 ttaaagagta tga atg etg aac atg caa eaa cat etc tet get ate gee 354 Met Leu Asn Met Gin Gin His Leu Ser Ala Ile Ala age ctg. Se: Leu as cge aac caa etg Arg Asn Gin Leu gcg gge eac att Ala Gly His Ile aac ctt act gac Asn Leu Thr Asp 402 450 tc Phe 2.00 tgg ege gaa get Trp Arg Glu Ala gag Glu 105 teg ctg aat gt Se: Leu Asn Val cct Pro 110 cit gig aeg eca gtc Leu Val Thr Pro Val 2.15 gaa gga geg gaa Giu Gly Ala Glu gat Asp 2.20 gag cga gaa gtg Glu Arg Giu Val ace Tbhr 1.25 itt etg tgg ege Phe Leu Trp Arg gee ega Ala Arg 2.30 eat oct ctg His Pro Leu gag eac gta Giu His Val. 150 gge git tat etg Gly Val Tyr Leu cgCt Arg 140 ctg aac egg gig Leu Asn Arg Vai aeg gat aaa Thr Asp Lys 145 aeg gat ate Thr Asp Ile gaa aaa gga aig Giu Lys Gly Met age gce ett ccc Sex Ala Leu Pro gaa Giu 160 igg aca Trp Thr 1.65 ctg aca ctg egi Leu Thr Leu AXrg tta Leu 170 cdc gea agt tac Pro Al1a Ser Tyr ige Cys 175 ggc tee tat teg Giy Ser Tyr Ser cig etg gaa ate ceec ec ggc act aeg get Leu* Leu Glu Ile Pro Pro Gly Thr Th: Ala gag acg att gca cig tcc G2.u Thr Ile Ala Leu Ser 180 185 ttt gee acc ctt gce gga aag gcc gat ccg eta aac aaa 738 gga ggc cegi Gly Gly Ar-g atg ccg gag Met Pro Giu Lys Ala Asp Pro Phe Ala Thr Leu Al1a Gly 200 205 gca aag gaa tea Ala Lys Giu Ser aac gtt egg gga Asn Val Ar-g Gly aac Asn 220 210 gtg ctg aca Val Leu Thr 225 ttc cac ace Phe His Thr 786 ctt, gat aaa Leu Asp Lys 230 get ccc gee ctg Ala Pro Al1a Leu tcg Ser 235 gaa tgg aac ggc Giu Trp Asn Gly gga caa Gly Gin 245 ctg ctt ace icc Leu Leu Thr Ser atig Met 250 cge att atc gee Arg Ile Ile Ala ggg aaa ict egC Gly Lys Ser Arg 255 cag ccc etc ggg Gin Pro Leu Gly cag Gin ctg Leu 275 882 930 978 gt Val 260 cgg ctc tat att Arg Leu Tyr Ile ccg Pro 265 gat git gat at Asp Val. Asp Ile gte gig cig CCC Val Val Leu Pro ggt gaa ace igg Giy Giu Tbh: Trp, iii Phe 285 gat eac ctt gge Asp His Lou Giy gia, tge Val Cys 290 gcg gca ati Al1a Ala Ile gta ctg ggc Val Leu Gly 310 gac Asp, 295 goc gee ata aai Ala Ala Ile Asn aat As n 300 ggg cge ate gig Gly r; Ile Val ccc gig gct Pro Val Ala 305 gag ata etc Giu Ile Leu 1026 10714 ait gac aac att Ile Asp Asn Ile aai 315 gaa cat gaa cgc Giu Hi3 Giu Ar; act Thr 320 gge ggg Gly Gly 325 ege age aaa eig9 A.rg Ser Lys Leu aag gat ate gc Lys Asp Ile Ala cat ci; cig cog His Leu Leu Pro aig at cgc get gaa met Ile Ar; Ala Giu 340 caa cog cag egi, ca; Gin Pro Gin Ar; Gin 345 cag agc etc ggc ggg Gin Ser Leu Giy Gly 365 tgg T rp 350 gca gac cgt ic; Ala Asp Arg Ser cgc Ax g 355 1122 1170 1.218 aca gig ci; gcc Thr Vai Leu Ala ate agt gcg cia atg ggg Ile Ser Ala Leu Met Giy 370 get cgi. tac gca ccg gaa acg tic Al1a- Arg Tyr Al1a Pro Giu Thr Phe ggt cig gig cic agc cac tci cct. Gly Leu Val Leu Ser His Ser Pro 1266 375 caa tgc Gin <210> 28 <211> <212> PRT <213> Escherichia cci. 38038 385 1272 <400> 28 Gly Lys I His Ser Ala Leu Ile Val Ala His Arg Leu Thr Thr Ala Gin A.rg Cys Asp Gly Th~r His Leu Ile Ala Val Ile Asp 25 Lys Gly Leu Leu Ala Giu Tyr Thr Arg Leu Giu Gin Leu Leu Ser 40 Ala Gly Gly Leu Tyr Trp His Asp Ser Val. Ser Se: Thr Ala Leu His Gin His Asn Met Glu Giu Thr Pro G1 y <210> 29 <211> 317 <212> PRT <213> Escherichia coli <400> 29 Met Leu Asn Met Gin Gin His Leu Ser 1 5 A-la 10 Ile Al1a Ser Leu Arg Asn Gin Leu Ala Ala Glu Ser Gly His Ile Ala Asn Lau Thr Asp ?he Trp Arg Giu Gly Ala Giu Leu Asn Val Pro Val, Th~r Pro Val GlU Asp Glu Arg Giu Val Thr Phe Leu Trp Ar; Ala His Pro Leu Gin Gi y Val Tyr Leu Arg Asn ArgVal Thr Asp 75 Lys Giu His Val Glu Lys Gay Met Met Ser Ala Leu Pro Giu Thr Asp lie Trp Thr Leu Thr Leu Arg Leu Pro Pro Gly 115 1a Thr Leu Ser Tyr Cys Ser Tyr Ala Leu Ser Leu Leu Glu Ile 210 Ser Gay Giy Arg Phe Thr Ala Glu 225 Met Ala Gay Lys 130 Asn Val Ala 135 Lys Pro Leu Asn Lys 140 Thr Pro Giu Ile Arg Gly Asn Ala 150 Trp Glu Ser Val Leu 155 His Leu Asp Lys Ala 160 Ala Leu Ser Asn Gly Gly Phe 170 Ser Thr Gly Gin Leu Leu 175 Thr Ser Met Ile Pro Asp 195 Asp Gv Glu Arg 280 Val Ile Ala Gly Lys 185 Pro Arg Gin Vai Asp le Ser Gin 200 His Leu Giy Leu Val 205 Ala Ar; Leu Tyr 190 Vai Leu Pro Ala Ile Asp Thr Trp Phe 210 Ala Ala Asp 215 Arg Leu Gly Val Cys 220 Ala Ile Asn Asn 225 Asp Gly 230 His Ile Val Pro Val 235 Val Leu Gly Asn Ile Asn Glu Ar; Thr Glu 250 Leu Ile Leu Leu Pro Lys Leu Ile Glu Gin Pro 275 Gly Gin Ser 290 Lys 260 Gin Ile Ala Gly His 265 Asp Gly Gly Ar; Ser 255 Met lie Ar; Ala 270 Thr Val Leu Ala 285 Ala Ar; Tyr Ala Ar; Gin Trp Ala 280 Ser Ar; Se: Arg Leu Gay Gly Ile 295 Ala Leu Met Gly 300 Glu Thr Phe Gly Val Leu Ser His Se: Pro Gin 315 <210> 2 11 <212> <2i3> 4039 Escherichia cold <220> <221> CDs <222> (285) <220> <221> <222> CDs (370) .(1326) <400> co-t tca aig tgg Pro Ser Met Trp I acg cca gaa aga Tb: Pro Giu .Axg ace agt cga cca ggc tig ttO Thr Se: Axg Pro Gly Leu Phe agc gaa ace Ser Giu Th: &cc tca tgg gtg Thr Ser Tzp Val a gi Ser gag cat ctg ott Giu His Leu Leu tot gco oca Se: Ala Pro cog cag ggc Pro Gin Gay gta cgt ato age Val Arg Ile Se: tgc gtg gga tog ctg gaa ggt tog Cys Val Gly Sex Leu G2.u Gly Se: aca gtg Tb: Val ct cac gtt cag Pro His Val Gin ca g Gin 55 ctt cac cag cgg Leu His Gin Arg oig Leu att aoo got ggo Ile Tb: Ala Gly cat tao goa tgg Asp Tyr Ala Trp s0 1.92 240 285 gaa ago oat tgo G2A2 Ser His Cys gea Ala ate tao ace ggt Ile Tyr Tb: Giy ggt oao Gly His tgg ogo ggt go-a Trp Arg Gly Ala ctg att Leu Ile gao ggg att Asp Gly Ile ggt tta Giy Leu 90 eta eag ggt tga Leu Gin Gly gttgacecae aaacaotttc aggaaacggt acagaettoo tgaataaato aaatagtoac 345 ctgeggaaaa ggaataatca toag atg tat gee ego gag tat ego tea aca 396 Met Tyr Ala Arg Glu Tyr Arg Se: Thr 100 ego cog oat aaa gcg att ttc ttt cat ott tot igo etc aoc cit ate 444 ALrg Pro His Lys Ala Ile Phe Phe His LeU Se: Cys Leu Tb: Leu Ile 105 110 115 120 igit agt gcg caa git tat gc; aag ccg gat at; eg; cea ctg ggg cc9 cys Ser A2.a Gin Val Tyr AlIa Lys pro Asp Met A-r; Pro Leu Gly Pro aat at~a gc Asn lie Ala tc aac tot Phe ALsp Ser 155 gat Asp 140 aaa ;;c Lys G.1y tee gig itt tac cat tic agc gtc ace tot Ser Val Phe Tyr His Phe Ser 145 150 acg gcc gig Thr Ala Val gic gat ggo aca Val Asp Gly Thr cgc Ar; 160 cat tat cgg gta His Tyr Arg Val g Trp 165 cc; aai Pro Asn 2170 aca aco gca ccg Thr Thr AlIa Pro gca AlI a 1175 icg ggi iac cc; Ser Gly Tyr Pro ait ita tat at; ctt Ile Leu Tyr Met Leu 180 gaa ctg cto aaa caa Glau Leu Leu Lys Gin 636 684 732 gao Asp 185 ii; Leu ggi aaO gca gtt Gly Asn Ala Vali tca gaa a& aca Ser Glu Lys Thr 205 at; Met 190 gat cgc ci.; gat Asp Ar; Leu Asp gao Asp 195 cc; cca. gig ate Pro Pro Vali Ile gig Val 21.0 got gic ggg tat Ala Val Gly Tyr cag ace Gin Thr 215 aac etc ct Asn Leu Pro goa gaa agc Ala Giu Ser 235 ite Phe 220 gat cic a&o age Asp Leu Asrz Sex ag; Ar; 22.5 got tao gac tat Ala Tyr A-sp Tyr ac; oca gca Thr Pro Ala 230 agc cgt aag Ser Ar; Lys 780 828 aga aaa aca gat Ar; Lys Thr Asp cic Leu 240 cac ica. ggg cgt His Se: Giy Ar; ttt Phe 245 agt 9gt Se: Giy 250 gc ago aao aac Giy Se: Asn Asn tic Phe 255 cgc ca; tia ct; Arg Gin Leu Leu gaa Giu 260 aeg cgt at. ;cC Thr Ar; Ile Ala aaa gig gaa cag Lys Val Giu Gin ct; aat ate gat 1,eu Asn Ile Asp Cg; Ar; 275 caa cgc ogc ggc Gin Axrg Ar;g Gly tia Leu 280 8'76 924 972 igg cac icc Trp Giy His Ser ggc cic tic Gly Giy Leu Phe gig Val 290 ct; gat tee igci; icc Leu Asp Ser Trp Leu Ser 295 tcc tot tac Ser Ser Tyr tc Phe 300 ogg ic; iac tao Ar; Se: Tyr Tyr agc S er 305 goc ago cc; to; Ala Ser Pro Ser t; ggc aga Leu Gly Ar; 310 1020 ggt tat gat get tig cta agc cgc git acg gcg gtt gag ect ctg caa Gly Tyr Asp Ala Leu Leu Set Arg Val Thr Ala Val Glu Pro Leu Gln 1068 tic igc Phe Cys 330 gat aac Asp Asn aaa cac ctg Lys His Leu atgq gaa ggc Met Glu Gly teg Ser 340 teg Set aca cag ggt Thr Gin Gly eog gaa acg Axg Glu Thr gte ggg gig Val Gly Val 345 ace Thi ctg Leu 355 aat Asn aaa att cat Lys lie His ace Thr 360 etc act ata Leu Thr le gat aaa ggc Asp Lys Gly gte Val 37 0 tie Phe gee gia ttt Ala Val Phe iog gat Trp A-Sp 37 11.16 1164 1212 1260 2.308 tie eec aac Phe Pro Asn cig Leu 380 eac ggg ceg His Gly Pro agi ggt gaa Ser Gly Glu aat gee tee Asn Ala Ser iii cgc cag Phe Arg Gin 390 gea ggt tgt Ala Gly Cys gca ci~g tia gat aic Ala Leu Leu Asp Ile 395 cat gag tia age cac His Glu Leu Ser His gca aat tac aca Ala Asn Tyr Thr taa acactgceg ettttacgcg ggeagtacge 1356 cigaaaeaet tiataggiat ccgacatiaa taagegeeca gta egeggtt atggtceagt gtgtctti itecaccagig igccactiga atcttatict acgatcagaa tegceette gacgcagatt getetttacc tgicigc iaagcgagtt geteegaagt ggaaagacat, ggataiatgc ggtaatcatt igatgeggta agaagategg tttattaata taacagaccg atataacgtc attgatagta gateatecat act ggei'tcg gectgaagcg gcggaagtag acteeggeat aagatctgtt tegtaattga ecagiattt cagttgacgc tatttcggga giggcatigg aiaccgtcca gtigcega gtcacacttg agtaagcccg tattgaggat 4ritcgteee Cctgcgggt tggcagaaaa tgaeegaeag tattceagit ccagagetit taacgttatc cgtggtaatc gcigqcteg 1416 attaetgaeg 1476 eaccagtgaa 1536 ttegcatga 1596 cgeeigggtg 1656 aggataceg 1716 cagaegatet 17176 ccgecatte 1836 cceggccacg 1896 ttcccaggtg 1956 aactccagcc caatttctit attgacgctg attt~ceggat Cgagatcttt attaccgatc 2016 aggtagcacc cgcctgatgt aatatctttt ggacagccat tgcctttcga gtagagcaga 2076 taaccttcac actttgaaat tggattgata aatcgcccaa caggt-,tggg ttcctgcgaa gctttaaaag agattcagac ttcgggcaac tgggctgaa gagtcgctga gataatcaaa gcqcaggccg ggaatgatat tcacccag atgltatctt gcagaaccag ca ata taca g aaataccgct cgcactgatt gatatcactg tgaaaatgat tcatteaccg tcaicgagct tatcgcggtt ccacictgca ccaac-ggtca ttcaaagga ttttca ccc tia ttggtt, tagcgtaatgi gctttt eggi gcggctatat gccgttaata agaattaata aagagcatta atcgctactt acgt-tggta agggccgcgg gcgggiatca accatcaatt tattaagctc ctaaaatacg tetcg-taata cataattctg aactgcactg ccggcttcga tcitigitac tcccaactgt cgCCactggtt ccettca cca aacaccaaag tcggtacagg gaagaactgt aatcgagaat gtaccccttc cagcatccgt cgccaogaac ccgccggata cga ctttgtc cggctcgtct tttgcgtatc cigct gcgga atgcccggct tttatteaga ttttactgc'. tcaggctggt gcgtttgatc icaggcgatt atecttCait cccagtceca cttgtgccgg gccgeataga tttaatttcc gcgtttttcg ttaccataca gcgcgacgcg :cgtgccagt gaaccgtagc gcacccagi ttacgtgacg Ccctgcitttg 22.36 gttcccgccg 2196 aaccggctca 2256 gcgatccgca 2316 agaggaagga 2376 aaccatcaca 2436 qgtcgtaaac 2496 catgcgggta 2556 gataccatta 2616 attttccag 2676 tattcccctg 2736 acgagacaac 2796 taccgaccgg 2856 aacgcgtggt 2916 tagcgccctc 2976 :gttggtggg 3036 ;cgccgccgc 3096 -ggtgtcacc 3156 caccggtac 3216 tctggcggtt 3276 ccagccagag gcccactaag gctgaaattg tccggctga-, atgatgttca atcacttcaa cgcictceac aaaattaagg tggtgtataa ccaccccccc ta cgctcaac gcca gcta ta tgttttctgg cgacagcgaa ggctgccccc Ctgttccggt acgcacggag ccccatacca cgaatatcga gttaccgcgt gtgcccgagg cgctattgcc ggiaagattg acgccaggca ttttacgaat 3336 aaiatctgaa aggtcgttta ccggaggggt Ctttttaata tcctcgctgg taataaccga 3396 cacgcccggc attaicatcg agttagcgac aaaatgtttg tiaiaiaaga aataiatcga tacticagic actcatccg ggtgcgcttg ttictaa cct gictttctgc tgctgtttta tcggaggatt cagaggattt atcgtiaagc atgataatia ttittIcataa a aa iaa att gcaaagtcag icgatcatcg gcaiittcag aacactactg ataccigetc tggciactga tgttaattct tcacatcctt atatcatia atatcaaati ctgaagcact taccgttcai ggaatltigt acacgggcgc ctttcaacaa agcggtggct tacctggcia catacctatt gccagatatt gcaaaagaaa gataiataac gcta gtagig cttttgtact cacaatttct tgctia igia ggtcaggcat iccaccacca ttcaacccaa ccciaataaa itttacigcc aagcaatccc atatgitt-tt ccagttcAgc gatgtigcca aacggatagt tataagatca ttc gagtctcgtc ccaggagcac togcctaacti attatigtt tcacaagata tatttcattg itcttig ctggaaaatc gttcacattg gcatcactag 3456 3516 3576 3636 3696 3756 3816 3876 3936 3996 4039 <210> 31 <211> 94 <212> PRT <213> Escherichia ccli <400> 31 Pro Ser Met Trp Trp Th: 1 5 Ser Giu Thr Asn Thr Se~ r Pro Giu Arg Thr 10 Glu Ser Arg Pro Gly Leu Phe rTrp Val His Ijeu Leu Val Pro Gin Gly Thr Val Pro Arg Ile Ser Leu Leu Val Gay Ser Ser Ala Pro Glu Giy Ser Thr Ala Giy His Val Gin Vai Giu Gin 55 Ile His Gin Arg Leu His Ser His Cys Trp Aila 70 Ile Tyr Thr Giy Asp Tyr Ala Trp, Axg Gly Ala Leu Asp Gly Ile Giy Leu Gin Gly <210> 32 <211> 318 <212> PRT <213> Escherichia coli <400> 32 Met Tyr Ala Arg 1 Glu Cys Tyr Arg Ser Thr Arg Pro His Lys Ala Ile Phe Phe His Leu Lys Pro Asp Val Phe Tyr Ara His Tyr Ser Met Leu Thr Leu Ile 25 Pro Leu G1V Pro Arg Cys Ser Ala Gin Asn Ile Ala Asp Phe Asp Ser Val Val Tyr Ala Lys Gly Sex Asp Gly Thr 40 Thr His Phe Ser Arg Val Trp Pro Ile Leu Ser Ala Val Pro Gly Tyr Tyr Met Leu Arg Leu Asp Val Ile Val 115 Ser Arg Ala Asp 100 Ala Glu Asp 90 Leu Asn Thr Thr 75 Gly Asn Ala Ser Glu Lys Val Ala Pro Met Asp Leu Lou Lys GIn 105 Thr Val Gly Tyr Ala Gin 120 Pro Asn Lou Pro Phe 125 Arg Thr Pro Pro 110 Asp Leu Asn Lys Thr Asp 130 His Ser Gin Leu Tyr Asp Tyr Giy Arg Phe 150 Leu Glu Thr Thr 135 Ser Ala Ala Glu Se: 140 Gly Arg Lys Ser Ser Asn Asn Arg Ile Ala 165 Gin Pro 170 T rp Val Gu GIn Asn Ile Asp Leu Phe Val 195 Arg 180 Leu Arg Arg Gly Leu 185 Ser Gly His Ser Tyr 190 Arg Gly Leu 175 Gly Gly Se: Tyr Asp Ser Trp Leu 200 Giy Se: Se: Tyr Phe 205 Ala Tyr Ser 210 Ala Ser Pro Sex Leu 215 Arg Gly Tyr Asp 220 Leu Leu Se: A-rg Val Thr Ala 225 Ile Met Glu Gly Val Ser 245 Glu Pro Leu Gin 230 Ala hr Gin Gly Phe Cys Ala Lys His Leu Ala 235 Asn Arg Giu Thr 240 pis Ala 255 Vai Gly Val Lys Gly Vai 27 5 Leu 260 Ser Lys Ile His Thr 265 Thr Leu Thr Ile Leu Lys Asp 270 Gly His Gly Asn Al1a Val Phe Trp 280 Asp Phe Pro Asn Leu 285 Pro Met 290 Phe Asn Ala Ser Ala Asn Tyr Thr 32.0 Arg Gin Ala Leu Asp Ile Ser Gly Asn A-1a Gly Cys His Giu 315 Leu Ser His <210> 33 <211> 3292 <212> DNA <213> Escherichia Cai <400> 33 ccgctgcggt attcaataaa aggcagait tttttcagga tagcocacgc cccOccgttt taaggttgCt ccgttgagga gatgtciggi ccaggatgcc tcacatttac ccttcccatg ccttccggac tccagtct gaggtgcgCg ccacgagtgc taacgccat gcaatggctt ttttggaigt cgccattcgg ttctgcggct tagc~ctgat tgattgccgg ttgcagcgtt cagcgatagc tctccatata cgatagagtc gcattactgt gaaicaggac agtagtgctc ccacaccatc ccgccagat-c gcggttggat tagaaccttt cgttatcaga iatacagatt ccggagagct cgtaatagag attccatcca cctgttcacc attcagaacg tatacatatc gcga ciectt cgigeagcaa atacggcgtg ctgtaggctg gccggctiag cgcgtgcatt gctttCCtgC gccggtgaat gtgatacttg ggccttacgg gataaa ggig caccgccgta catgcctttc cgcaccgcgg ggtgaacaca ggcgaagata acccgcatat gaagaaaggc gcgttgatcc gccgcgcacg agccgggctc ggacaccgag gttttccccc ct~gcggcagc aacgcctiat gataagatgc tca gatttaa tcggtctgta ggatcggtgt cca ccctgat aactcatcca ttagactgac gttttcggta gggaagagat cagtaaacga aacggegtgc atcagcgtgt tcgttcatct tt-ggcgt6tcg ttatcactct aggtctteca gcaigaacgt agggcgactt ttaaagccgc atatgccatt gtggttaacc ccggcctaca gtcagcatcg tctgcgcgCg qcggtacacc acaggtiaaa atccgctctg tacgcacagc catttgttCC ct-aaaticgc ccoccagatc aggitggcac gaccgigcgg tatcaagctg ccaccatgca ggiagttatc tcgccatctt tatatit-cgg catctttgct ccgggttgac ggaaatcaic tcccgatagc cttgcagacc atcatigcaa catccggcaa 120 tggjtggatat 180 catcggaata 240 caccgac-gat 300 ggtataageg 360 agaaagttta 420 caggaagaaa 480 tactt-tcgcc 540 gacaatgccg 600 acgaacgccg 660 cggaacttcg 720 accgtttttc 780 gtcgccgtaa 840 gaagigacag 900 gtcgaggaac 960 cataatgtcg 1020 gaacggcagt 1080 atgaacatca 1140 aaagccaacg 1200 cigggtgacg 1260 gcccggttgc 1320 ccgacatig gcgcgggttg gcaacggcgt aegtccatec tttttctcaa accgatca tcgtatccgg atgagaggaa atgcaaaatg agatccctct ttatccagaa gatattgt~a ggcattaata aattgtgcgC cagaaitatc aacgagtaga gacocagagC ac-accaigga gcctgctccg gcctccgggt cgcgacoCat atgcgtaatc cctgccattC cgcccacgtt gttttcagac atcaatcata igccacctoc caaaccttca ticcageatt atccagcagc ttccggatgg ttcattacgg9 ggccagctcc gcggCatCag gggaagaact cgatatcgg agcccacaic gttccgccag tgttgtcggC caaagcctt gagctgcggc ctccggtttc ccctcacagg atgaatigaa ggcggtgatg iatatgtiat aggagaaata icataacaag tgctcattcc cgtttaeggt cacaacgttg taataagagc gagaaagagc cgctgcgget gtaggcgtc tccgtgtttc tttgatctgt gccggggatc atttgctggg aaggccacct ciaccgttat gcacqatgtt gaactcatg cgtggcgtaa gccagttgca gctgcgcgtt aatgecgtgg cggttgagaa tgta gggita a tccagcaag tticgctgg aatagtggtc gcgtgcggtg gacaccaaca atgtcgtcaa atgattgcat aaatcaggag tiatatcgcg taaitgaatg ttcactcagg tgttaaggga getta tcgic agtgaagcac aggcgttttt tactgiggcg tcttccggct ggacgttgtt atcagcgact tggcgcagca ggcagcagca cagtatcatg gatgacgcgt eggcacgcgc ctteatcacc caccagtgcg ctt6ccagcag gacgtacacg ccagatgttg tggatggagt tacgccgaag cccaccgcca aaaacaacca gtt tctiigt gccoggtttaa gcggttgacg a ca agaa gtt aatgatgacg aaataatagt agcattitea ttgatta'tg acttttatta a agtta ttac tg-tatttc ticgccttag cactgacaga ccacttgttg ttataiatca ggitgttctg tgtgcagtct icagcgctgc gacccagtgt ctttttccaa ggccgaateg atcgtcacac tttccggctt ctgaiccatc aacatgggct gatatacgcc cttatccacg ggtgatttct gttggcgcgjt attgtccggt ttaaaatcag cgccgCcgCC cgttcggttt cttgtgcagg ccagatacig gggtatctgc tgggtogaaaa taaitaagca gaiaaaaata atcctacct-c atgctgttlt ttcattatat tcaggaagca cggttctctg tgcctcataa tgtcgcttat tcatacagac gaaaggcccc caacgttaac gtccagcgcg geggaaggcg getccac-aac gctgttCccg tcatactggc tcaataagat iggtttttcc aggccaatc ttcgccattg tgttccgcca ccgtgacgtg accggaatgg gjcttcag cat gagaatcgig 1380 cccctggctg 1440 gmtaaagcca 1500 cttaccggtt 1560 atgctgcatc 1620 gtttgggtga 1680 tgcgctggct 1740 cgaaaattcc 1800 itgataatig 1860 aattatttat 1920 tggcgcaggt 1980 -attaac 2040 aiaigtgtag 2100 aagaggatta 2160 tggcataata 2220 actccggaat 2280 gcctcatcaq 2340 ctgttttaac 2400 ggaggtgctt. 2460 atcaaaccgt 2520 tcggcaagcc 2580 agcgatgctt 2640 agcgggcgat 2700 ggttaattgg 2760 gtticaggcc 2820 gjttccgccat 2880 accagttacg 2940 atgcctgttg 3000 aigggatgat 3060 gacgiaatac 3120 ctgcaiggtt 3180 tgtcattgcc 3240 cc 3292 <210> 34 <211> 11165 <212> DNA <213> Escherichia coli <220> <221> CDS <222> (3791)..(4834) <220> <221> CDS <222> (10459).. (107"76) <220> <221> <222> CDs (10134) .(10427) <220D> <221> CDs <222> (9836) (10081) <220> <221> Cns <222> (7816) .(9480) <220> <221> <222> <220> <221> <222> <220> <221> <222> CDS (4 87 8) 0 8 (702) CDs (3460) (3702) CDs (3054).. (3407) <220> <221> CDs <222> (2613). (3041) <220> <221> <222> <220> <221> <222> <220> <221> <222> <220> <221> <222> <220> <221> <222> CDs (2198) (2530) CDs (1939) (2196) CDs (1573) (1893) CDs (1102) (1485) CDs (1099) 400> 34 c a~cgat aig cag cgc ggt ate cag get gea acg get gca ctt cag ggc 49 Ser Asp Met Gin Ar; Gly Ile Gin A2.a Ala Thr Al.a Ala Leu Gin Gly ctg gtg ggc Leu Val Gly gag cig go; Giu Leu Ala aat aig gca Asn Met Ala gge gcg Gly Ala etg gca ggt get Leu Ala Gly Ala tca gcg cog Ser Ala Pro gac aat aca Asp Asn Th~r 97 145 aac atc ate ggt Asn Ile Ile Gly cat His cac gcg ggt att His Ala Gly Ile go; gca Ala Ala so aaa gee att gcc cat gee att ctc ggt Lys Al1a Ile Ala His Ala Ile Leu Gly 55 ggt Gi y gtg aca gca gcc Val Thr Ala Ala cag ggc aae agt Gln Gly Asn Ser gcg Ala gca gea ggc gca Ala Ala Gly Ala ggt, geg ggt act Gly Ala Gly Thr 241 289 gaa gtg atc gc9 Glu Val Ile Ala tea Ser gcc ait gcg aaa Ala Ile Ala Lys age Ser 90 etc tac cog ggc Leu Tyr Pro Gly gta gat Val Asp cc; tog aaa Pro Ser Lys acg ctg tea Thr Leu Ser 115 etg Leu 100 aca gaa gat cag Thr Giu Asp GIn aag Lys 105 eaa act gta GIn Thr Vali gcg ggt at; gee Ala Gly Met Ala ggC Gi y 120 ggc att goc agt Gly Ile Ala Ser age aeg ctg gca Ser Thr Leu Ala 110 ggc gat gt; get Gly Asp Val Ala 125 gtt gag aat aat Val Giu Asn Asn 337 385 gge geg Gly Ala 130 gct get gga get Ala Ala Gly Ala 9gt Gi y 135 gee ggg aag aae Ala Giy Lys Asn gtt Val 140 geg Al1a 145 ct; agt et; gtt Leu Se: Leu Val gcc Ala 150 aga ggc tgt go; Arg Gly Cys Ala gca gca cot tge Ala Ala Pro Cys agg A.rg 160 433 481 529 act aaa gtt gca Thr Lys Val Ala cag ttg eta gaa GIn 1.eu ILeu Giu ate Ile 1,70 ggg gcg aaa go; Giy Ala Lys Al1a ggc aig Giy Met 175 gee ggg ctt Ala Gly Leu ggg gc; goa gtc Gly Al1a Ala Val aag Lys 185 gat at; gcc gac Asp Met Al1a Asp agg aig ace Ar; Met Thr 190 577 tec gat gaa Ser Asp Giu 195 ctg gag cat cig Leu Glu His Leu att Ile 200 ae cig caa Thr Leu Gin aig atg Met Met 205 ggt aat gat Gly Asn Asp gag atc Giu Ile 210 act act aag tat Thr Thr Lys Tyr agi tcg ttg cat Ser Ser Leu His aag tac ggt icc Lys Tyr Gly Ser get gcc icg aat Ala Ala Ser Asn ccg Pro 230 aat ate ggt aaa Asn Ile Gly Lys gat A.sp 235 cig ace gat gcg Leu Thr Asp Ala 67 3 '721 '769 617 aaa gta gaa cig Lys Val Glu Leu 9gC Gly 245 ggt tec ggc tea Gly Ser Gly Ser ae ggt aca eca Thr Gly Thr Pro cca eca Pro Pro 255 aag cti Lys Leu tcg gaa aat Se: Glu Asn aat cag aag Asn Gln Lys 275 gat Asp 260 cci aag cag caa Pro Lys Gin GIn gaa aaa act gia G2.u Lys Thr Val caa ga~a agt geg Gin Glu Sc: Ala aag aag ate gat Lys Lys Ile Asp aac Asn 285 act aia aaa Thr Ile Lys aat gct Asn Ala 290 cig aaa gat cat Leu Lys Asp His gat Asp 295 att att gga act Ile Ile Gly Thr etc Leu 300 aag gat aig gat Lys Asp Met Asp gat cat atg cag Asp His Met Gin 320 ggt Gi y 305 aag cea gtt cct Lys Pro Val Pro aaa Lys 310 gag aai gga gga Giu Asn Gly Gly tat igg Tyr Trp 315 913 961 1009 gaa aig caa aat Giu Met Gin Asn acg Thr 325 cic aga gga tta Leu Arg Gly Lcu aga Arg 330 aat cat gcg gat Asn His Ala Asp acg tig Thr Leu 335 aaa aac gic Lys Asn Val gat gct at Azp Ala Ile 355 ait ace tia Ile Thr Leu 370 aac Asn 340 aat cct gaa get Asn Pro Giu Ala get geg tat Ala Al1a Tyr aat aaa ata gaa Asn Lys Ile Glu. egt aaa ttg att Arg Lys Leu Ile tca Ser 360 gga Gi y 375 gee iig aaa gga Al-a Leu Lys Gly aac aic. aat aig Asn Ile Asn Met ggc aga gca aca Giy Arg Ala Thr 350 tat gga. at aig Tyr Gly Met 365 aca, aaa gag Cc Thr Lys Giu Pro 380 1057 1104 1152 gag caa G2.u Gin 385 caa tca ccg ct Gin Ser Pro Leu ctc tgg tic gaa Leu Trp Phe Giu cgt aic Arg Ile 395 ata gat gig Ile Asp Val cct Pro 400 ctt gaa aag tta Leu Glu L.ys Leu gig gaa gat cii Val Glu Asp Leu cgc gei aie cga Arg Aia Ile Arg 1200 1248 1296 aai tia tgt at Asn Leu Cys Ile cag tig aig cca Gin Leu Met Pro gig ttg gaa gt Val Leu Giu Val cia act Leu Thr 430 gag ccg Lys GIU Pro tta tca acg Leu Ser Th~r 450 iia Leu 435 gcg ggt gaa tat Al.a Gly Glu Tyr tac Tyr 440 gat ggt. gaa cia Asp Gly Giu Leu att. gca gei Ile Aia Ala 445 agi ace i~tt, Sex Tki: Phe 1344 ata aaa gga gaa gat cta aaa gat cag le Lys Gly Glu Asp Leu Lys Asp Gin 455 aaa Lys 460 1392 ae caa Thr Gin 465 ata agg caa ct Ile Arg Gin Leu ata Ile 470 aac cag eta gaa Asn Gin Leu Giu ccg Pro 475 tca gat ait aac Sex Asp Ile Asn 1440 gat tia aga aaa Asp Leu Arg Lys gat aia Asp Ile 485 ta aaa Leu Lys aic aat le Asn 490 cag ata at gta Gin Ile Ile Vai 1485 taaciaaicc cggccaciga gccgagatct ictgigig ccgggcaigi icagcagcii 1545 gggggiaaaa gicccctgte cagccig aig gig gcg aag gcg ttc geg tac gca 1599 Met Vai Ala Lys .Ala Phe Ala Tyr Ala cii aac Leu Asn 505 cag igg ccg gca Gin Trp Pro Ala ctg Leu 510 acg iac tat gcg Thr Tyr Tyr A-1a aac Asn 515 gat ggc tgg gig Asp Gly Trp Val ga a Glu 520 g gt Gly ate gac aac aac Ile Asp Asn Asn cqi. aaa aac iic A.rg Lys Asn Phe 540 atic Ile 525 gct gaa aat gcc Ala Glu Asn Ala cig Leu 530 cgg gcg gic agt- Arg Ala Val Ser 1647 1695 1743 ci.g itc tic ggc Leu Phe Phe Gly tct Ser 545 gac cai ggt. ggi Asp His Gly Gly gag egg Giu Arg 550 gga gcg cta cig iac agc cig atc ggg acg igc aaa cig aai gac gig 19 1791 Gly Ala 1,eu Leu Tyr Sex Leu lie Gly Thr Cys Lys Leu Asn Asp Val. 555 560 565 g at oca gaa age tac ctt cgc cat gig cit goc gic at& gca gac tg; 1839 Asp Pro GlU Ser Tyr Leu Ar;9 His Val Leu Ala Val Ile Ala Asp Tro 570 575 580 ccg gtc aao cgg gic agc gaa cig cit ccg tgg cgO aia gca cig cca 1887 Pro Val Asn Arg Val Ser Giu Leu Leu Pro Trp Arg Ile Ala Leu Pro 585 590 595 g ct gaa Ala Giu 600 aig tct Met 5cr 605 iaacacatcc ccgicaaiac ggccctcgct giacgctiac agaaa aig ct; 1944 met Leu gia cag aaa gaa Val Gin Lys Giu aaO gic gca gag Asn Val Ala Glu gig gia tot gaa Val Val Ser Giu 1992 2040 acg Thr 620 cat aoc ggc gao His Thr Gly Asp ago Ser 625 gia tat got Vai Tyr Ala too cig ttt gaa aaa ait aac Ser Leu 630 Phe Glu Lys Ile cig aat cc; gia Leu Asn Pro Vai ici Ser 640 goc ctg agi gca Ala Leu Ser Ala Cig Leu 645 gat aac cot tic Asp Asn Pro Phe egg iea A-rg Ser 650 2088 goa gat aac Alja Asp Asn cag igo gca Gin cys Ala 670 go; Al1a 655 act ggo aga at Thz Gly Arg Ile arc Thr 660 icc ago ata caa Ser Se Ile Gin oct go; qgg Pro Al1a Val 665 cgg caa icc A~rg Gin Ser 2136 2184 got got goa gca Ala Ala Al1a Ala act Thr 675 gag ggt tot tgt Giu Gly Ser Cy's ccc Pro 680 cc; tgt Pro Cys 685 tca gga a at; gig gat aac ig; cag aag agi gia agg agi cgt 2233 Ser Gay Met Vai Asp Asn Trp Gin Lys Ser Val Ar; Ser Arg g cg Ala 700 cic cog gaa Leu Pro Giu gag go; Giu Al1a 705 got gag Al1a Giu 720 at; ac; ggc igg aao gaa ggo at; atc cgc 2281 Met Thr Gly Trp, Asn Glu Gly Met Ile Ar; 710 '715 tia cag cag t; Leu Ginl Gin Leu ogo ci; Ar; Leu aac cgm cag gat gaa cag egg gga Asn Ar; Gin Asp Giu Gin Ar; Gly 725 730 2329 aaa tac at; acg gtc agi gaa ci; aaa ac; gag gig itt ggc atc at; 2377 Lys Tyr Met Thr Val Ser GiU Leu Lys Thr Giu Val Phe 735 aac egg cat ate Asn Arg His Ile 740 geg gaa gag cag Ala Giu Giu Gin Gly Ile Met egi cgc tac Arg Arg Tyr cag get ttt Gin Ala Phe 750 cog Pro 755 2425 ggt gaa Gay Giu 765 gte call aac cag Val Arg Asn Gin ggc agt gaa cag Gly Ser Giu Gin caa aaa cag get Gin Lys GIn Ala 2413 2521 gaa Gi u *78 0 atg gcg eta aat Met Ala Leu Asn ca g Gin 785 tta att aac cgt Leu Ile Asn Arg tat 790 eag atg ata cgt Gin Met Ile Arg gea Ala 795 ggc aaa caa Gly Lys Gin tagtggtagc eataatgeag gageaaagc tgaateagga 2570 2624 agattattc tgactgagtt tggttttctg gcgattttg tg atg gtg Met Vai Boo gga tgt Giy Cys get tgg tta Ala Tr-p Leu 805 get gaa cag gee Ala Glu GIn Mla tec gac cat geg Ser As;> His Mla ctt Leu 815 tea eca cac 5cr Pro His 2672 agt get Ser Mla 820 tgg ceg tac agt Trp Pro Tyr Sex teg cgc gat gee Se: Arg Asp Aia ggg Gay 830 ctg gee gat aeg Leu Ala Asp Thr gee gac gac ace Mla Asp Asp Thr 850 g ge Gi y 835 geg ggc gge tat Ala Gay Gay Tyr act tgt aaa cag Thr Cys Lys Gin egg tgg Arg Trp 845 2720 27 68 2816 gtt ggg ctg aaa Val Gly Lieu Lys gee Ala 855 egt eta ctg eaa Arg Leu Leu Gin ctt Leu 860 cot gee eta gat Pro Ala Leu Asp ate tgg Ile Trp 865 aeg gcg ttt Thr Mla Phe gtg ctg ego Val Leu Arg 885 aaa ate gac eag Lys Ile Asp Gin teg Sex 875 eag gta gtg tat Gin Val. Vai Tyr gaa gag gee Giu Giu Ala 880 teg eag aat Ser Gin Asn 2864 2912 tog egg gte agt 5cr Axg Vai Se: gaa Glu 890 ega aat atg eag Arg Asn Met Gin gta Val 895 ggc Gay ggg ego gtt tat eca ago tat ggc ggt aae gtt gat Gay Arg Val Tyr Pro Ser Tyr Gly Giy Asn Vai Asp ace gte gee Thr Vai Ala 2960 905 910 aat gce gcc ace egg ttg gca tec ggc gct Ala Ser Gly Ala As n 915 Ala Ala Thr Axg a ga Arg 925 aat ate etc qg agc Asn Ile Leu Gly Ser 930 3008 ata gcg gca igt Ile Ala Ala Cys acg gca Thr Ala 935 tie gac age Phe Asp Ser gig Val 940 cgt taggeactac cg atg gia 3059 Arg Met Val eag gcg Gin Ala 945 cag ctg caa ata GIn Leu GIn Ile 9gg Ala 950 etg gig ate tgt att ceg etg ata acg Leu Val Ile Cys Ile Pro Leu Ile Thr 955 etc Leu 960 tgt tog gcg tgg Cys Ser Ala Trp ga t Asp 965 gtg aaa gia gig Val Lys Val Val aeg Ctg acg tt Thr Leu Thr Phe g Val 975 315 3203 cag ttt gca eta Gin Phe Ala Leu ttt Phe 980 tic etc ace ttt Phe Leu Thr Phe tgg 'rrp 985 tgg gaa cig gca Trp Glu Leu Ala egg tgg Arg Trp 990 cit gat age Leu Asp Sex age tgg aat -Ser Trp Asn 1010 g Trp 995 cig etg gat gig etc Leu Leu Asp Val Leu 1000 tac aac age gat Tyr Asn Ser As; ace cac agi Thr His Se: 1005 gig att ate Val Ile Ile 3251 3299 tia gee ggg Leu Ala Gly ate cag Ile Gin 1015 aat aeg cag gat Asn Thr GIn Asp gac Asp 1 020C aat ctg gig Asn Leu Vai 1025 ggg geg atg Giy Ala Met 1040 atg agg Met Arg ttg aig Leu Met 1030 itt cig gig ttg ceg Phe Leu Val Leu Pro 103~5 aca tic tgg ctg Thr Phe T-p, Leu 3347 3395 aeg igg get gga gig agg Thr Trp Ala Gly Val Arg 1045 gt-t gge gig geg ctg aat gga Vai Giy Val Ala Leu Asn Gly 1050 1055 gcg Ctg geg gga Ala Leu Ala Gly igattgggag gtgatt.cgcc aatctcactt teetatacac 3447 3498 ataiaaaatg ta aig aaa tat etc ttt tti gag aat ata eat tct ata ttt Met Lys Tyr Leu Phe Phe Giu ALsn Ile His Se: Ile Phe 1060 1065 1070 tia aca tie agi etc tie ega aca ict gig tog cct gat tic eca aig 3546 Leu Thr Phe Sex Leu Phe Arg Thr Ser Val Ser Pro Asp Phe Pro Met 1075 1090 1085 att ttt gca tig ccc tca atc att tta ggrt caa itt acg ace aac caa Ile Phe Ala Leu Pro Ser Ile Ile Leu Gly GIn Phe Thr Thr Asn Gln 1090 1095 1100 tta act aac ttt gtg ata igt aig ggt aac ace gtt gaa ogi cgg ctg Leu Thr Asn Phe Val Ile Cys Met Gly Asn Thr Val Glu ALrg Arg Leu 1105 1110 2.115 1120 ggt gtt gtt cat aat ccc tti aaa agg tot ggg gat ggc cat gac ctc Gay Val Val His Asn Pro Phe Lys Arg Se: Gly Asp Gly His Asp Leu 1125 1130 1135 agrg gog gia gog tgaccaaagt tcataicoat accaatiati. tattiaaa Arg Ala Val Ala 1140 atatcaaoit aticgagttg tttiatttag ttcaaagaag gtaicaaa ttg ata gt Leu Ile Val 3594 3642 3690 3 7 42 3*79 9 3847 ata gat tti ttt le Asp Phe Phe 1145 igt ggc tgi Cys Gly Cys S1150 ggt 99a gec agt gaa ggg cia ogi cag Gly Gly Ala Se: Glu Gly Leu Arg Gin 1155 gct ggc Ala Gly 1160 iii gat Phe Asp aic gag Ile Glu 1165 ott gga ita Leu Gay Leu gat ait gac Asp Ile Asp 1170 caa caa gca tea GIn Gin Ala Ser 11.75 3895 gaa aca iiit Giu Thr Phe aaa got Lys Ala 1180 aai tic cot Asn Phe Pro gat gca Asp Ala 1185 aaa tic atc Lys Phe Ile caa gat gat Gin Asp Asp 1190 3943 att agg aaa ate Ile Arg Lys Ile 1195 gaa cci caa Giu Pro Gin gat atc Asp Ile 1200 too gac atv at igat Se: Asp le Ile Asp 1205 att aaa le Lys 3991 gct aaa cgg cci tig ita cig agt Ala Lys Arg 1.210 tog caa cag Ser Gin Gin 1225 cia. aat gaa Leu Asn Giu 1240 Pro Leu Leu Leu Ser 2.215 gca igi gca oca igt Al1a Cys Ala Pro Cys 1220 caa cca ttt Gin Pro Phe 4039 aat aaa Asn Lys aat aaa Asn Lys 1230 act agt gao gao ica agg aga aat cia Thr Ser Asp Asp Ser ALrg ALrg Asn Leu 1.235 4087 aot oat ogi, iii ait aga Thr IHis Arg Phe Ile Arg 1245 gaa ciit cit cot Glu Leu Leu Pro 1250 gaa tat at Glu Tyr Ile 1.255 4135 atg ctt gaa aat gtt Met Leu Glu Asn Val 1260 cet gga atg caa aaa Pro Gly Met GIn Lys 1265 att gat gaa gaa aaa gaa Ile Asp Giu Giu Lys Giu 127 0 4183 g9c eca ttt cag Gly Pro Phe Gln 1275 gag ttt att Giu Phe Ile aag cta Lys Leu 1280 Ctt aaa gag Leu Lys Giu tta gag tat aac Leu Glu Tyr Asn 1285 4231 tat ata tct ttt ata gce aat get Tyr Ile Ser 1290 Phe Ile Ala Asn Ala 1295 gag aac tat ggg att Giu Asn Tyr Gly Ile 1300 ccc caa aga Pro Gin Arg 4279 aga aaa Arg Lys 1305 cca gag Pro Giu 1320 gat tat Asp Tyr aga Ctc gtg Arg Leu Val ctc tia Leu Leu 1310 gct agt cga gia ggt Ala Ser Axg Val Gly 1315 aaa gtt ace eta Lys.Val Thr Leu 4327 ata ace cat ggt aaa aat le Thr His Giy Lys Asn 1325 aaa ate cca ttc aaa act gta cga 4375 Lys Ile Pro 1330 Phe Lys Thr Val Arg 1335 ate cag gac Ile Gin Asp 1340 tic aca aag Phe Thr Lys ita tgt Leu Cys 1345 tea gga gaa ace gac ccc Ser Giy Giu Thr Asp Pro 1350 4423 aaa gat Lys Asp cet tia Pro Leu 1355 eat agg gct His Arg Ala gga aca Giy Thr 1360 etg age cci. Leu Ser Pro cit aac Leu Asn 1365 eta aaa Leu Lys 4471 451.9 aga att atg cac act cea. gaa gga ggg gat aga aga aat tgg cca gaa Arg Ile Met His Thr Pro Giu Gly Giy Asp Arg Arg Asn Trp Pro Giu 1370 1375 1380 gag tta Giu Leu 1385 tat gga Tyr Gay 1400 git eat aaa Val Asn Lys tge cat Cys His 1390 aaa aat tat Lys Asn Tyr gat ggc Asp Giy 1395 eac aca gat act His Thr Asp Thr 4567 4615 aga atg agt tgg gat aag Arg Met Ser Trp Asp Lys 1405 cci gcg ect, Pro Al1a Pro 1410 aca ett aeg Thr Leu Thr aeg aaa Thr Lys 1415 tgt aat agt Cys Asn Ser tac ice aat ggt Tyr Ser Asn Gay .1420 egt tit ggg cat Arg Phe Giy His 1425 gaa gca tea age Giu Ala 5cr Arg 1440 cci. gae ccc act caa Pro Asp Pro Thr Gin 1430 tie. caa aca ttt cet Leu Gin Thr Phe Pro 1445 4663 cat aga gca ait age ate aga His Arg Ala Ile Sex Ile Arg 1435 4711 tta agc tat gtt ttt aaa og tcg cig aat tea atg gca aag caa atc Leu Ser Tyr Val. Phe Lys Gly Ser Leu Asn Ser Met Ala Lys Gin Ile 1450 1455 1460 4 75 9 ggc aat gct gia ci tgc gaa cic gct aga cta ttt ggg cta cat ctc 4 807 Gly Asn Ala Val Pro Cys Glu Leu Ala Arg Leu Phe Gly Leu His Leu 1465 1470 1475 ata gaa aat tgt act aat aag gat ica tagatataig gctaaaataa Ile Glu Asn Cys Thr Asn Lys Asp Ser 1480 1485 4854 gaacaaaggc tcgagctttg gac atg ctt ggc aga caa caa ait gca ggi ata 4901 Met Leu Gly Arg Gin Gin le Ala Gly Ile 1490 1495 ect act Pro Thr 1500 gat aat Asp Asn 1515 gee tig agt gag ita Ala Leu Ser Glu Leu 1505 gic gaa gtt gat ttt Val Glu Val Asp Phe 1520 itt aaa Phe Lys itt agg Phe Arg aat act cat Asn Ala His 3.51.0 gat gee tat get Asp Ala Tyr Ala 4955 aaa gaa Lys Glu 1525 aat cit cii Asn Leu Leu atc tig Ile Leu 1530 5003 aga gat gat Arg Asp Asp gga tta Gly Leu 1535 ggt atg aca Gay Met Thr ace gat Thr Asp 1540 gaa ttt. gaa Glu Phe Glu ttg act ait 99a acc tce agc aaa tta atc gac gat gat Leu Thr Ile Gly Thr Ser Ser Lys Leu Ile Asp Asp Asp gag agg tgg Glu Arg Trp 1545 gca ati aat Ala Ile Asn 1560 atg gga gag Met Gly Glu 5052 5099 1550 1555 aaa cca gca Lys Pro Ala 1565 aaa gga ata Lys Gly Ile 1580 gtt cit act Val Leu Thr 1595 gtg gat agt Val Asp Ser aat aaa Asn Lys 1.570 gee tit cgc ca~ atc Ala Phe Arg Pro Ile 1575 5147 5195 ggc cgt tia tci Gly Arg Leu Ser 1585 atc gca gca att gga Ile Ala Ala Ile Gly 1590 cca cag gig ctg Pro Gin Val Leu agg gcc aaa aga gac aat Arg Ala Lys Arg Asp Asn 1600 gag eti Giu Leu 1605 aag cca tta gtt get Lys Pro Leu Val Ala 1610 5243 gca itt gtt aat tgg agt ita Ala Phe Val Asn Trp Ser Leu 1615 iii gct ata cca tca cit gat cit gat Phe Ala Ile Pro Ser Leu Asp Leu Asp 5291 .1620 1625 gat ata gaa ata Asp Ile Giu Ile 1630 eca att aga act ati Pro Ile Arg Thr Ile 1635 ate aac gac gaa tac ttc act Ile Asn Asp Glu Cys Phe Thr 1640 5339 aaa aaa act Lys Lys Thr 1645 ctt gat gag Leu Asp Giu aig att Met Ile 1650 gag caa gca aga aat Giu Gin A.la Arg Asn 1655 aat tta gac Asn Leu Asp 53867 tet tt~a Ser Leu 1660 caa tia Gin Leu 16*75 tca cac aaa ata tea Ser His Lys Ile Ser 1665 aaa tca aaa gta tea Lys Ser Lys Val Ser 16'70 caa ata aat aca Gin Ile Asn Thr tea tct ttt Ser Ser Phe gaa ttt gat cct Giu Phe Asp Pro L680 tct gga gat qg Ser Gly Asp Giy att cia le Leu 1685 tgg gaa aaa Trp Giu Lys *aaa tta Lys Leu 1690 *ata ata Sle Ile 1705 5435 5483 5531 ggt ggg cia Gly Giy Leu aga cta Arg Leu 1695 cat His 1700 gga act cac tic Giy Thr His Phe atg cci ae gaa Met Pro Thr Giu 1710 gaa ata tia ata gat Giu Ile Leu Ile Asp 1715 gac att tce aec Asp le Ser Thi fagc gat age Ser Asp Ser 1720 tta tta ggt Leu Leu Giy 55'79 56277 aat aaa. aca Asn Lys Thr 1725 tea gag cag Ser Giu Gin ict it Ser Ser 1730 cgc ita gaa A.rg Leu Giu aaa get Lys Ala 1735 ttt aca Phe Thr 1740 tt aga Phe Ar-g 1755 aac aea atg Asn Thr Met tac agt Tyr Ser 1745 gat tea aac cci cci Asp Ser Asn Pro Pro 1750 ait ata gct cgt Ile Ile Ala Arg 56*75 gac tat Asp Tyr cig gaa Leu Giu 1*760 gat ggt gag tge ati Asp Giy Giu Cys Ile 1,765 gic aga ait age gaa Asp Arg Ile Ser Giu 1770 5723 tea ait tt Ser Ile Phe ttt aca Phe Thr 1775 ccg caa gaa tic aat Pro Gin Glu Phe Asn 178 0 cit gca cat cac cac ait Leu Ala Asp His His Ile 1785 5771 gaa gga tgg tic aat gaa iii Giu Giy Trp Phe Asn Giu Phe 1790 ggt caa Giy GIn .1795 te agt gga act Phe Ser Gly Thi *git tet gt Vai Ser Val 1800 5819 tat ggi gaa gag eca ait cat eat qtc gig act igg aaa aai aat aat Tyr Giy Giu Giu Pro Ile His His Vai Val Thr Trp Lys Asn Asn Asn 5867 1810 1815 caa tia Gln Leu 1820 ggt cgg Gly A-rg 1835 ace caa tgc ggt cca Tkir Gln Cys Gly Pro 1825 tit aaa ata aaa tta Phe Lys Ile Lys Leu 1830 gog tat att cat Ala Tyr Ile His 5915 cit cat gat ica Leu Arg Asp Ser 1840 ogO tta CCC Axrg Leu Pro atg gag Met Glu 1845 tig 1gg cc Leu Tr-p Ala cct cig Pro LCel 1850 aag gag aaa aca gat Lys Glu Lys Thr Asp 1855 aga tat ggt ggt tta tat Axrg Tyr Gly Gly Leu Tyr 1860 ate tat cga gat gga Ile Tyr A-rg Asp Gly 1865 5963 6011 6059 tia aga att tig Leu Arg Ile Leu 1870 coo tat gga Pro Tryr Gly gat tca Asp Sex 18*75 gat acg gat Asp Thr Asp itt cta Phe Leu 1880 aaa ata Lys Ile gaa aag aga Giu Lys Arg 1885 aga acg tia tee got Arg Thr Leu Sex Ala 1890 tot gaa tat Ser Giu Tyr itt to Phe Phe 1895 toa tat Cga Ser Tyr Axrg 6107 cgt ttg Axg Leu 1900 itt gga gca ata gaa Phe Gly Ala Ile Giu 1905 tta aca aaa gaa aao aat got ica tia Leu Thr Lys Glu Asn Asn Ala Ser Leu 1910 6155 qit gaa aaa Val Giu Lys 1915 get ggg oga Al1a Gly Arg 1920 gaa gga to Giu Gly Phe ait gaa Ile Glu 1925 aat aag oca Asn Lys Pro tat aaa Tyr Lys 1930 6203 cag ttt aaa gaa aig Gin Phe Lys Giu Met 1935 ctt gaa aat tic tic aie Leu Giu Asn Phe Phe le 1940 gaa atc gca aga cat Giu Ile Ala Arg Asp 1945 6251 tt ttt aag gao Phe Phe Lys Asp 1950 gat ggc gat atg tot Asp Gly Asp Met Ser 1955 gaa tia tA-t Giu Leu Phe gtt gag aca aag Val Giu Thr Lys 1960 6299 caa ogt Gin Arg act aaa Thr Lys 1980 a ga Arg L 965 aat gaa gaa cat gat Asn Giu Glu His Asp i970 ttg tia tot aaa aga 1,eu Leu Ser Lys Arg 19,75 tot aaa caa 5cr Lys Gin got aaa aaa gat aga Ala Lys Lys Asp Arg 1985 tta aag aaa gat cig tat gat tt ttt Leu Lys Lys Asp Leu Tyr Asp Phe Phe 1990 6395 gat aag ita Asp Lys Leu 1995 gat aat gat tao tgg Asp Asn Asp Tyr Trp 2000 aat att gaa ata aat aag ota aic Asn Ile Giu Ile Asn Lys Leu Ile 6443 2005 2010 aat aaa aac gag gaa Asn Lys Asn Glu Giu 2015 a ta gat tat gi-a tac Ile Asp Tyr Val Ayr 2030 tat tic tce agt aca gaa ata aca gac acc aat Tyr Phe Ser Ser Thr Glu Ile Thr Asp Thr Asn 2020 2025 6491 aat aaa att aaa Asn Lys Ile Lys 2035 gaa caa aat gat get ate att Giu GIn Asn Asp Ala Ile Ile 2040 6539 aaa aat cia Lys A sn Leu 2045 cgt aat tct Arg Asn Ser gig gat Val Asp 2050 ata aag aaa Ile Lys Lys ccc ict Pro Se: 2055 gga gtt oga Gly Val Gly 6587 tta aca Leu Thr 2060 caa aaa Gin Lys 2075 aaa gag tta Lys Giu Leu tct aat Ser Asn 2065 ita .igg gat Leu Trp Asp aat gag cta Asn Glu Leu aga tat Ar-g Tyr 2070 caa ata gaa aga Gin Il.e Glu A-rg ata ctg tia tca cta Ile Leu Leu Ser Leu 2080 aaa. Lys 2085 gat aac gjtt gat aga Asp Asn Val Asp Arg 2090 6635 6683 6731 aag ctt ata gaa ctg Lys Leu Ile Giu Leu 2095 gat aat aaa aat aat Asp Asn Lys Asn Asri 2100 gat itt etc aac tta cgg Asp Phe Leu Asn Leu Arg 2105 aag aga cit gaa Lys Arg Leu Giu 2120 gat ict tig aat cia. Asp Ser Leu Asn Leu 2115 caa caa agi Gln Gin Se-- tac tat gaa aaa Tyr Tyr Giu Lys 2120 6779 gaa cta aca Glu Leu Thr 2125 caa ict aaa Gin Ser Lys 2140 aag tia tat aat gac gct Lys Leu Tyr Asn Asp Ala 2130 aaa. aat got ttg aaa gat gig Lys Asn Ala Leu Lys Asp Val 2135 6827 oca aat agg tia Ala Asn Arg Leu 2145 ati tct gat Ile 5cr Asp aat aag aaa Asn Lys Lys 2150 aaa cat aag Lys His Lys 6875 agi gaa Ser Giu 2155 ggc aaa Gly Lys cta aaa aac ati Leu Lys Asn Ile 2160 gai act gcg tat Asp Thr Ala Tyr 2175 tct tat gaa, tic caa Ser Tyr Giu Phe Gin 2165 ata ttg gat gta aaa, Ile Leu Asp Val Lys 2180 ica act aat Ser Thr Asn ctc &at Leu Asn 2170 6923 6971 aga aat cta gaa, agi ALg Asn Leu Giu Ser 2185 aaa ati gag aat act tca aac gaa Lys Ile Giu Asn Thr Ser Asn Giu 2190 gig atti aat gaa. ata aga aaa cta Val Ile Asn Giu Ile Ar-g Lys Leu 7019 2195 2200 acc gac cag Thr Asp G2.n 2205 att gca at~a att agt Ile Ala Ile Ile Ser 2210 gat agt acc act ict Asp Ser Th: Th: Se: 2215 gaa aat tta Glu Asn Leu '70V7 tca tcg Ser Se: 2220 cga gac Arg Asp 2235 gct caa gta Ala Gin Val act gaa Th: Giu 2225 gca atc gaa Ala Ile Glu act gaa Thr Giu 2230 ctt gaa cat tta Leu Glu His Leu 71115 7163 caa caa gca aat Gin Gin Ala Asn 2240 aac gca gag Asn Ala Giti tia ata Leu Ile 2245 cia ctt. ggc 1.eu Leu Gly aig gct Met Al1a 2250 cti tct gia Let Ser Vali agt gcg cia Ser A .la Leu gat at ata Asp Ile Ile 2285 gia cat Val His 2255 cat gaa tt His Glu Phe aat ggt Asn Gly 2260 aat at agg Asn Ile Arg agg Arg 2270 gaa tia aaa Giu Leu Lys gca tgg Ala Trp 2275 gct gac aga aat Ala Asp Arg Asn gea at aga Ala Ile A.rg 2265 cct aag ctt Pro Lys Leu 2280 ita gat ggt Leu Asp Giy 7211 7259 7307 tac caa aaa aic aga Tyr Gin Lys Ile Arg 2290 act agi ttt cat Th: 5cr Phe Asp ca c His 2295 tat tia Tyr Leu 2300 acc aat Tb: Asn 2315 aaa acc tt Lys Thr Phe ata act gga Ile Th: Gly aca cca Thr Pro 2305 ttg aca aga cgt ita Leu Th: Arg Axrg Leu 2310 agi cgc ict aaa Ser Axg Se: Lys -act Thr 2320 gcc at tia Ala Ile Leu gaa iii Giu Phe 2325 atc aga gat gta tic Il.e Arg Asp Vai Phe 2330 7355 7403 7451 gat gat cgt ct gag Asp Asp Arg Leu Giu 2335 aaa gaa gga att gaa Lys Giu Gly Ile Giu 2340 tia itc act acc ica aag Leu Phe Th: Th: 5cr Lys 2345 iii gt aat caa gaa at gia act tac Phe Val Asn Gin Glu Ile Vai Tb: Tyr 2350 2355 aca ica ace Thr Ser Thr att iac cci, gic Ile Tyr Pro Val 2360 ggg aaa aca act Gly Lys Thr Th: 2375 '7499 iii ata aat Phe Ile Asn 2365 cia ati. gat Leu Ile Asp aac gca As n Al a 2370 ata tac igg ctt Ile Tyr Trp Leu '75 47 gga gaa aaa aga ctt aia cti gat gct act gaa aca gga ttt git at Gly Giu Lys Arg Leu Il.e Leu Asp Ala Th: Giu Thr Giy Phe Val Ile 7595 2380 2385 2390 ggt gat act ggt ccc ggt Gly Asp Thr Gly Pro Gly 2395 2400 gat at; gga ttt aca cga Asp Met Gly Phe Thr Arg 2415 gtt tea act aga gat Val Ser Thr Ar; Asp 2405 aaa aca gga agg cgt Lys Thr Gay Gly Ar-g 2420 cga gat ata ata tt Arg Asp Ile Ile Phe 2410 gga at; gga tta tic Gly Met Gay Leu Phe 2425 17643 "76 91 att icc aaa gag tgt Ile 3cr Lys Giu Cys 2430 tta tct ega. gat ;ga ttt act ata aga ttg gat Leu Ser Arg Asp Gly Phe Thr Ile Axg Leu Asp 2435 2440 *7 73 9 gat tac act cct Asp Tyr Thr Pro 2445 gaa aca agt gaa Giu Thr Ser Giu 2460 gaa cag ggt get tic tt Giu Gin Gay Ala Phe Phe 2450 att att gag eca tea gaa Ile le Giu Pro 3cr Glu 2455 7787 tag cggatataaa taa atg aca age tet act cat ttt Met Thr Ser Ser Thr Asp Phe 2465 2 47 0 cat aaa ct His Lys Leu tet gaa Ser Giu 2475 gac tgc gtt egc cgt Asp Cys Vai Ar; Ar; 2480 ttt tta eat tet gta gt Phe Leu His Sc: Val Val 2485 18 84 get gta. gat gac Ala. Val Asp Asp 2490 aca gac gaa gat Thr Asp Giu Asp 2505 aat at; t Asn Met Ser tit gga. Phe Gay 2495 get ggt agi Ala Gay Ser gat act te cet Asp Thr Phe Pro 2500 '7932 "7980 att aat get tta Ile Asn Ala Leu 2510 gtt gat ccc Val Asp Pro gac gat Asp Asp 2515 gat cct aca Asp Pro Thr eca ata Pro Ile 2520 aaa ;ea Lys Ala 2535 ata aca gca Ile Thr Ala tea gca 3cr Ala 2525 tee eca ata gaa. 3cr Pro Ar; le Giu 2530 tea act aaa tea Sc: Thr Lys Ser get cta. gca gaa Ala Leu Ala Giu 2550 8028 aag gta aaa, aae Lys Val Lys Asn 2540 cat cci ttt His Pro Phe gat tac eaa, Asp Tyr Gin 2545 8 07 6 8124 get ttc gee aaa gat Ala Phe Ala Lys Asp 2555 ggt att get tgt tgc Gay Ile Ala Cys Cys .2560 gga tta tta Gay Leu Leu get aag agt Ala Lys 3cr 2565 ttt aat gtt gaa gaa aga. gat ata att aca gca tea tcc cac aag gca Phe Asn Val Giu Giu Ar; Asp Ile Ile Thr Ala Ser Ser His Lys Ala 8172 2570 2575 2580 gat ata sa Asp Ile Thr 2585 ais ctt gac tgg gat Ile Leu Asp Trp Asp 2590 atg caa agc gat agt Met Gin 5cr Asp Ser 2595 ggg caa ttt Gly Gin Phe 8220 gct at Ala Ile 2600 gga cgt Gay Arg 2615 gaa. ata ata Giu le Ile aaa teg Lys Ser 2605 ata atc gtt le Ile Val tea gat Ser Asp 2610 ata aat tct gga Ile Asn 5cr Gly 8268 8316 tta cat ctt ctt Leu Arg Leu Leu 2620 tet ait tat Ser Ile Tyr act ggt Thr GI y 2625 gas cat gt Giu His Val act get Thr Ala 2630 gtt ais act Val Ile Thr ata ass sat Ile Lys Asn aag tig Lys Leu 2635 aac sat gag Asn Asn Glu tia sag 1,eu Lys 2640 as sea tac Lys Thr Tyr egt agc gia Arg 5cr Val 2645 gca etc gas Ala. Leu Glu 2660 8364 8 412 gat Asp 2650 gat agi att ttt att Asp Ser Ile Phe Ile 2655 gaa. gat aac tat Giu Asp Asn Tyr ca tg Gin Trp, cca aai Pro Asn 2680 tee aac Ser Asn 2695 igat Cys 665 aia git git sit agt Ile Vai Val Ile Ser 2670 aaa, gac gtt tat gaa Lys Asp Val Tyr Glu 2675 ass gat ct Lys Asp ILeu gig tta aia. aaa ass Vai Leu Ile Lys Lys 2685 tic act sac ctt saa Phe Thr Asn Leu Thr 2690 get ggg tig eta, Ala Gly Leu Leu 8460 8508 8556 gee gca cic ici Ala Al1a Leu Ser 2700 ige att ict ga aia Cys Ile 5cr Giu Ile 2705 aga gaa. aaa ace cat Axg Glu Lys Thr His 2710 ggg ata ts sea ass Giy Ile Leu Thr Lys 2715 tat s~at aat aaa ita Tyr Asn Asn Lys Leu 2720 gac act ges Asp Thr Ala tea. agg gca Ser, Arg Al1a cac ate tsa sat His Ile Leu Asn 2730 ts ata asa tee sag gag Leu Ile Lys Ser Lys Glu 2735 tat git tee Tyr Val Ser 2'725 tat get tat Tyr Ala Tyr 2740 gsa ata aga Glu le Arg 8604 8652 8700 gaa aat get Giu Asn Ala 2745 cat gat tat ges gt. His Asp Tyr Ala Vai 2750 gat tia, sit tet gaa Asp Leu Ile Ser Giiu 2755 tea. ais tig caas ata, agt gas. sac ts sag ass ict eta age aaa, aac Ser Ile Leu Gin Ile Ser Giu Asn Leu Lys Lys Ser Leu Ser Lys Asn 8748 2760 2765 2770 icc t-a Ser lieu 2'77 5 icc cat tgg eci Ser His Trp Pro 27 80 ait ttt cac tat gca Ile Phe His Tyr Ala 2785 aaa aat ggt igi aag Lys Asn Giy Cys Lys 2 79 0 879 6 aat itt cta Asn Phe Lieu it-a act lieu Thr 2*795 aga aaa aaa Giy Lys Lys caa aaa Gin Lys 2800 gac t-a ica Asp Lieu Ser gta gaa cat Val Giu His 2805 8844 8892 cta agg aai ata Lieu Arg Asn Ile 2810 CtC ict gct Lieu Ser Ala gat it Asp Ser 2815 it-a gaa gaa Lieu Glu Glu ait caa cac gct le Gin His Ala 2820 at-i gaa cac Ile Giu His 2825 gca tct t-a Ala Ser Lieu ggi aaa .aag Giy Lys Lys 2830 gaa tac it-a agc caa Giu TIyr Leu Ser Gin 2835c gat ggt Asp Giy 8940 gaa gaa Giu Giu 2840 agg agi Ar; Ser 2855 gat aaa aag it-a aig Asp Lys Lys lieu Met 2845 caa it-a t-gc Gin Lieu Cys ici Ct-; Ser Lieu 2850 gaa atc acg cgc Giu Ile Thr Arg 8988 9036 t-a aga t-at cat Lieu Ar; Tyr His 2860 ici cat ata Ser His Ile gat aat Asp Asn 2865 gig t-ce ita Val Ser leu aaa caa Lys Gin 2870 gga act tta cit ita Giy Thr lieu leu lieu 28,75 gal, gca t-at Asp Ala Tyr aat t-i Asn Phe 2890 gic tat cta Vai Tyr leu t-gc ata caa Cys Ile Gin 2885 cca t-a t-gt Pro leu Cys 2 ctc agg gga leu Arg Gly 2905 gat Asp ~890 age gic aga tig cat Ser Val Arg leu His 2895 gaa aaa gcc Giu Lys Ala gat iii it-a it-c Asp Phe leu Phe 2900 9084 9132 9180 9228 aca ci; gac gat aai Th: leu Asp Asp Asn 2910 aai tac aai Asn Tyr Asn aaa at-; ccg Lys Met Pro itg it-a leu leu 2915 atc gaa gat Ile Giu Asp gaa t-at Glu Tyr 2920 at-i att Ile Ile 2935 qgc ggt t-i Giy Gly Phe tat aaa at-i Tyr Lys Ile 2925 g ca Al a 2930 aaa gct ict aat Liys Ala Ser Asn ica tii t-ca t-i gga Ser Phe Ser Phe Giy 2940 gic gaa aat gga Val Giu Asn Gly 2945 aac ggt gic Asn Gly Val ate ata Ile Ile 2950 ggg aaa aag aac aai cta gt- aat act gac tat atc ica t-c git cct Giy Lys Lys Asn Asn lieu Val Asn Thr Asp Tyr Ile Ser Phe Vai Pro 9324 2955 2960 2965 tta etc gtt gaa Leu Leu Val Giu 2970 aaa ata tet act cca aaa gia ttg aaa tgg Lys le Ser Thr Pro Lys Val Leu Lys Tr-p 2975 2980 atc Ogg Ilec Gly 9 37 2 gaa ata aaa Giu Ile Lys 2985 aca acg tac Thr Thz Tyr geg caa aaa A-1a Gin Lys 2990 ata aca act gat Ile Thr Thr A-sp 2995 att t e 12le Val Ala 9420 aat Ctg Asn Leu 3000 tea aga ata Ser Arg Ile ggt tia gat Gly Leu Asp 3005 caa cat gag tgg tta Gin His Giu Trp Leu 3010 caa ata aaa Arg Ile Lys 9468 tea aaa cat ata Ser Lys Asp Ile 3015 taaatgatta tatatgecgt egttttataa aaaetggcgg 9520 catgtatatc tagttagiee atcatagaag tcaagaaatt tagtttgeec tatatettat 9580 agaaaatata ttttatatgc ttaaaaaaca ceatctttct aagatggeat ttatgtgett 9640 tgtttcgatc aattacaact gatatattac catattgatt aattttatgt tatttaeeaa 9700 agtaacggea tcttaatata tcgteataat atagtgegeg ttctgaect aatactgaaa 9760 aatttattig ttctatttta caettactge aaatageatc cagtttatea tatagtgtc; 9820 catcaattgg egcag atg tea tea cgo met Ser Ser Arg 3020 caa ate ett gag cat tat aat get Gin Ile Leu Giu His Tyr Asn Ala 9871 3025 3030 eta aca tat c eta Leu Tkir Tyr Pro Leu 3035 cat caa tea His Gin Ser ate ttg ttg Ile Leu Leu 3040 eag Gin ata atg act teg Ile Met Thr Ser 3045 gag gat ate tee Giu Asp Ile Ser 3060 9919 9 967 aat ttg tta tea Asn Leu Leu Ser 3050 gtt tge act Val Cys Thr gga aaa Giy Lys 3055 tee att tac Sex Ile Tyr ggc ag-t tet Giy Sex Ser 3065 aga geg aga Axg A.1a ALrg 3080 tgg aat ate Trp Asn Ile ata cac tic Ile His Phe 3070 aat ate cet etc ecc Asn Ile Pro Leu Pro 3075 ate tet Ile Ser 10015 cttcte ata ttt iet tat Leu Se Ile Phe Sex Tyr 3085 tgt gte aga att Cys Val Arg Ile 3090 aaa. ect tgg Lys Pro Trp 10063 aig agt atg gat Met Sex met Asp tac atg taaceggetc atttaaaeeg tetggtetgt Tyr Met 10111 3095 3100 ttecccggt ttiacaaaaa ta atg ice ate att ttt aat gga cac tat cgt met Ser Ile Ile Phe Asn Gly His Tyr A-rg 3105 31.2.0 2.0163 atg aaa cac egg act Met Lys His Arg Thr 31125 tgg ate act gaa gct tta cgt ctt cac ttt gaa Trp Ile Thr Giu Ala Leu Arg Leu His Phe Giu

10212. 32120 32.25 gaa cat tia ccc Giu His Leu Pro 32130 cag gtt gig Gin Val Vai gte ggg Val Gly 32.35 cgt ege ctg Axrg Axg Leu gge gta cca aaa Gly Val Pro Lys 3140 2.025 9 ica aca get Ser Thr Ala 3145 igt ggt atg Cys Gay Met tic gig Phe Vai 32.50 cge itt cgc aaa get ggC itt tea Arg Phe Arg Lys Al1a Gay Phe Ser 32.55 10307 tgg eci Trp, Pro 32.60 cig ccc gca ggt aig Leu Pro Al1a Gay Met 32.65 teg gag egg Ser Glu Arg gag ct Glu Leu 32.70 gat gge egi ct Asp Gly Arg Leu 1.035 tac ggg agt ace tee aca Tyr Gay Ser Thr Ser Thr 31.75 3180 gia cct gtc gia eti igi agi gga tcg gia 1.04 03 Vai Pro Val Val Leu Cys 32.85 Ser Gly Sex Val2 32.90 ait cag gac ace Ile Gin Asp Thi :teg aaa tee 7Ser Lys Ser 3195 igt taaigttaaa aeagi.gaaaa igaggigaig cys 1.0457 c aig ate aaa act cgt egg act aaa egi ace itt tee ceg gag tie aag 2.0506 Met Ile Lys Thr Azg Arg Thr Lys Arg Thr Phe Ser Pro Glu Phe Lys 3200 3205 3210 cit gaa Leu Giu 322.5 get tic gag cag Ala Phe Giu Gin 3220 gaa gte geg cag gca etc Giu Vai Ala Gin Ala Leu 3235 ata egg tig tat aag cag Ile Arg Leu Tyr Lys Gin 3250 gig gig git aaa tac Val Val Val Lys Tyr 3225 gag etc aac cci gac Giu Leu Asn Pro Asp 3240 gaa cit cag ggi at Gilu Leu Gin Gay Ile 3255 cag egi gat gte aga Gin Arg Asp Val Arg 3230 cat ttg egi aaa tgg His Leu Arg Lys Trp 3245 gag cca get ggt aat Giu Pro Ala Gay Asn 3260 1.0554 1.0 602 1.0650 get ait accecci gaa caa ege gaa ait cag cag cit aaa geg cag ata Ala .Ile Thr Pro Giu Gin Arg Giu Ile Gin Gin Leu Lys Ala Gin Ile 1.0698 3265 aag cgc gtt Lys Arg Val 3280 aig agc gaa Met Ser Giiu 3295 aagtggccag caggtgaagc catccica tggcgttgat tcaacagccg tttactgaaC ttttattcg 32'70 32"75 gag aig gaa aaa gaa ata cta aag cag gct gcc gig ctg Glu. Met Glu Lys Glu Ile Leu Lys Gin Al1a Ala Val Leu 3285 3290 atc ccc ggg aag cig tc-g cgc taaicacaca gctgaaagca le Pro Gly Lys Leu Ser Arg 3300 tgtgggttat ttgicaitta ttcggiatta accgtagcgt ttattacg gtcctgttaa tgtgcaaaga attgaattac gaagc-cgggjt gagggctt gtcgtggcgc agccgggiag ccgggcaatc agtcagatgt tgcgccag gcaggccggt ggctggcatg acgactgatg cgggaatgag ggctgaca gttaaacaic acaaccgggt aaacgaagac aaaagtccgc cattgcca cggcaatittc accccgccgc accaaactgc gtctggtgeg gcgacatc cg ag ag *aa ag 10*746 10'796 10856 10916 10976 11036 11096 11156 11165 <210> <211> 366 <212> PRT <213> Escherichia coi <400> Ser Asp Met Gin Arg Gly Ile Gin Al1a Ala Leu Tbx Ala Ala Gly Leu Val Giy Glu Leu Ala Al1a Ala Lys Giy Asn Asn Met Al1a Gly Ala 25 F.is Ala Leu Gin Gly is Ala Ser Ala Pro Asp Asp Asn Thr Ile le Gly His 40 Ala Ala Gly Ile Vali Ala Ile Ala Leu Gin Hlis 55 Ala Ile Leu Gay Gi y Gi y Thr Ala Ala Gly Asn Ser Ala Gly Ala Glu Ile Leu Ala Gly Thr Val Ile Ala Ile Ala Lys Ser Tyr Pro Gly Val Pro Ser Lys Leu Thr Giu Asp Gin Lys Gin Thr Val Ser Thr Leu Ala 100 Thr Leu Ser Ala 115 Gly Ala Ala Ala Gay Met Ala Giy 120 Ala Gly Ile Ala Ser Gly Ala 130 Ala Leu Giy 135 Arg Gly Lys Asn Gly Asp Val Ala 125 Val Glu Asn Asn Ala Pro Cys Arg 160 Sex Leu Val Gly Cys Ala Val 155 G1y Lys Val Ala Glu 165 Giy Leu Leu Glu Ala Lys Ala Gly Met 175 Ala Gly Leu Ser Asp Glu 195 Giu Ile Thr Ala 180 Leu Ala Ala Val Lys 185 Thr Met Ala Asp Glu His Leu Ile 200 Ser Leu Gin Met Met 205 Lys Arg Met Thr 190 Gly Asn Asp Tyr Giy Ser Thr Lys Tyr 210 Giy Ala Leu 215 Asn Ser Leu His Ala Ser Asn 225 Lys Pro 230 Gly Ile Gly Lys Asp 235 Th: Thr Asp Ala Val Glu Leu Gly 245 Pro Ser Gay Ser Giy 250 Gly Thr Pro Pro Pro 255 Ser Glu Asn Asn Gin Lys 275 Asn Ala Leu Asp 260 Gin Lys GIn Gln Asn 265 Lys Giu Lys Thr Vai Lys Ile Asp Asn Glu Sex Ala Asp Lys Leu 270 Thr Ile Lys Asp Met Asp 285 Lys Lvs Asn, His 290 Gly Lys Pro Val Pro Lys Asp 295 Glu Ile Gly Thr Leu 300 Trp Asn Giy Giy 305 Tyr 315 Asn Asp His Met GIn 320 Leu Glu Met Gin Asn Lys Asn Val Asn 340 Thr 325 Leu Arg Giy Leu Arg 330 His Ala Asp Thr 335 Asn Pro Glu Ala Gin 345 Ala Ala Tyr Gly Arg Ala Th: 350 Asp Ala Ile Asn Lys Ile Giu. Ser Ala Leu Lys Gly Tyr Gly 355 360 365 <210> 36 <211> 128 <212> PRT <213> Escherichia coli <400> 36 Met Ile Thr 1 Leu Axrg Lys Leu Ile Gly Asn Ile Asn Met Thr Lys Glu Pro Giu Gin Gin Ser Pro Leu Giu Trp Ph. Giu Arg Ile Ile Asp Al1a Ile Arg Vai Pro Leu Giu Lys Leu Thr Val 40 Glu Asp ILeu Cys Arg Gin Asn Leu Cys Ile Asp Gin 55 Leu Met Pro Arg Val Leu Giu Val Leu Thr Lys GiU Pro Leu Ala 70 Giy Giu Tyr Tyr Gly Giu Leu Ile Ala s0 Ala Leu Ser Thr Ile Lys Gly Giu Asp Lys Asp Gain Lys Ser Thr Pb. Thr Gin Asn Asp ASP 115 ALrg Gin 'Leu Ile Asn 105 Gin Leu Giu Pro Ser Asp Ile 110 Ile Ile Val Leu ALrg Lys Asp Ile 120 Leu Lys Ile A~n Gin 125 <210> 37 <211> 107 <212> PRT <213> Escherichia coli <400> 37 Met Val Ala Lys Ala Phe Ala 1 5 Tyr Ala Leu Asn Gin Trp Pro 10 Al1a Leu Thr Tyr Tyr Ala Asn A-sp Gly Trp Val 25 Glu Ile Asp A.n Ansn le Al1a Glu Asn Ala Phe Gly Ser Leu Arg Ala Val Ser Leu Gly Arg Lys Asn Phe Leu Phe 40 Asp His G2y Gly Glu Arg Gly Ala Leu Leu Tyr Ser Leu Ile Gly Thr Cys Lys Leu 70 Asn Asp Val Asp Pro Glu Ser Tyr 75 Leu Arg Ser Glu His Val Leu Ala Ile Ala Asp TrP Val Asn Arg Val Leu Leu Pro Trp 100 Arg Ile Ala Leu Pro Ala Glu 105 <210> 38 <211> 86 <212> PRT <213> Escherichia ccli <400> 38 Met Leu Met Ser Val Gin Lys Glu Lys 1 5 Val Ala Gu Ser Val Val Ser Glu Thr Ile Asn Leu Thr Gly Asp Ser Val Tyr Ala Ser Leu Phe Glu Lys Asn Pro Phe Asn Pro Val Ser Ala Leu Se: Ala Leu Arg Ser Ala Asp Asn Ala Gin Cys Ala Ala 70 Thr 55 Gly Arg Ile Thr Se: 0E0 Ser Ile Gin Pro Ala Val Ala Ala Ala Thr Glu 175 Gly Ser Cys Pro Arg Gin Ser Pro Cys Ser Gly <210> 39 <211> Ill <212> PRT <213> Escherichia coii <400> 39 Met Val Asp Asn Trp Gin Lys Ser Val Arg Ser Arg Ala Leu Pro Glu 1 Glu Ala Met Ala Glu Arg Thr Gly Trp Asn Glu Gly Met 25 Ile Arg Leu Gin Gin Leu Leu Asn Arg Gin Glu Gin Arg Gly Tyr Met Thr Val Ser Giu Leu Lys Thr Giu Val Phe Gly lie Met Gin Ala Phe Asn Arg His Ile Pro Ala Glu 70 Giu Gin Leu Arg Arg .75 Tyr Gly Giu Val Arg Asn Gin Asn Gly Glu Gin Gin Gin Lys Gin Ala Giu Met Ala Leu Asn Gin Leu Ile 100 Asn Arg Tyr Gin Met 105 Ile Arg Ala Gly Lys Gin 110 <210> <211> 143 <212> PRT <213> Escherichia coli <400> Met Val Gly Cys Ala 1 5 Trp Leu Ala Giu Gin 10 Ala Pke Se: Asp His Ala Leu Ser Pro Leu Ala Asp His Ser Ala Trp Pro Tyr 25 Ser Ala Sex Arg Asp Ala Gly Gin Arg Trp Thr Gly Ala Gly Gly 40 Tyr Pro Tkr Cys Lys Ala Asp Asp ThX: Val Gly Leu Lys Ala Arg Leu 55 Leu Gin Leu Pro Ala Leu Asp Ile Trp Thr Ala 70 Phe Lys Lys Ile Asp '75 Gin Ser Gin Vai Val Tyr Giu Giu Ala Leu Arg Ser Arg Val Ser Glu Arg Asn Met Gin Val Ser Gin Asn 100 Gly Arg Val Tyr Pro 105 Ser Tyr Gly Gly Asn Val Asp 110 Gly Thr Val Ala Asn Ala 115 Ile Leu Gly Ser Ile Ala 130 <210> 41 <211> 118 <212> PRT <213> Escherichia coli Ala Thr Arg Leu Ala 120 Ala Cys Thr Ala Phe 135 Ser Gly Ala Ar; Asn 125 Asp Ser Val Ar; 140 <400> 41 Met Val Gin Ala 1 Gin Leu Gin Ile Ala 5 Val le Cys lie Pro Leu le Thr Leu Phe Val Gin ser Ala Trp Asp Val Lys Val Val Met Thr Leu Thr Glu Leu Ala Phe Ala Leu Phe Leu Thr Phe Trp Trp Arg Trp Leu Asp Ser Trp Leu 55 Leu Asp Val Leu Tyr Asn Ser Asp Thr His Ser Ser Trp Asn Leu 70 Ala Gly Ie Gin Asn 75 Thr Gin Asp Asp Val Ile Ile Asn Leu Val Met Arg Leu Met Leu Val Leu Pro Thr Phe Trp Leu Gly Ala 100 Met Thr Trp Ala Gly 105 Vai Arg Val Gly Val Ala Leu 110 Asn Gly Ala Leu Aa Gly 115 <210> 42 <211> 81 <212> PR? <213> Escherichia coli <400> 42 Met Lys Tyr Leu Phe Phe Glu Asn Ile His Ser Ile Phe Leu Thr Phe Ser Leu Phe Ar; Thr Ser Val Ser Pro Asp Phe Pro Met Ile Phe Ala 25 Leu Pro Ser Ile Ile Leu Gly Gin Phe Thr Thr Asn Gin Leu Thr Asn 40 Phe Val Ile Cys Met Gly Asn Thr Val Glu Ar; Ar; Leu Gly Val Val 55 His Asn Pro Phe Lys Ar; Ser Gly Asp Gly His Asp Leu Ar; Ala Val '70 75 Ala <210> 43 <211> 348 <212> PP.T <213> Escherichia cli <400> 43 Leu Ile Val Ile 1 Asp 5 Gi y Phe Phe Cys Gly Cys Gly Gly Ala Ser Giu G2.Y 10 Leu Ar; Gin Gin Ala Ser Gin Asp Asp Phe Asp Ile Giu Asn Gly Leu A-sp Thr Phe Lys Al a 40 Glu Phe Pro ALsp Ala Ser le Asp Gin Lys Phe Ile Asp Ile Ile le Ar; Lys Asp Ile Ile Pro Pro Gin Asp Lys Ala Lys Leu Leu Leu Gin Ser .7 5 Thr Cys Ala Pro Cys Pro Phe Ser Asn Lys Asn Lys Phe Ser Asp Asp Ser Ar; Ar; Asn Leu Giu Tyr le 115 Giu Lys Giu 130 Leu 100 Met Glu Thr His Arg 105 Pro Ile Ar; Giu Leu Giu Asn Val 120 Glu Gly Met Gin Lys 125 Leu 110 le Asp Giu Lys Giu Leu Gly Pro Phe Gin 135 Phe Ile Lys Leu 140 Giu *Tyr Asn Tyr Ile Ser Phe Ile Ala Asn Al1a Giu Asn Tyr Gly Ile Pro Gln Arg Arg Lys 165 Arg Leu Val Leu Leu Ala 170 Ser Arg Val Gly Lys 175 Val Thr Leu Thr Val Arg 195 Pro 180 Glu lIe Thr His Giy 185 Lys Asn Lys Ile Pro Phe Lys 190 Ser Gly Glu Asp Tyr Ile Gln Phe Thr Lys Leu Cys 205 Thr Asp 210 Pro Lys Asp Pro Leu 215 His Arg Ala Gly Thr 220 Leu Ser Pro Leu Asn 225 Leu Lys Arg Ile Met 23C His Thr Pro Giu Giy 235 Gly Asp Arg A-rg Asn 240 Trp Pro Glu Glu Leu 245 Val Asn Lys Cys His 250 Lys Asn Tyr Asp Gly His 255 Thr Asp Thr Thr Thr Lys 275 Tyr 260 Gly Arg Met Ser Trp 265 Asp Lys Pro Ala Pro Thr Leu 270 His Pro Asp Cys Asn Ser Tyr Ser 280 Asn Gly Arg Phe Gly 285 Pro Thz 290 Gin His Arg Ala "le 295 Ser Ile Arg Glu Ser Arg Leu Gin Phe Pro Leu Ser Tyr 310 Val Phe Lys Gly Leu Asn Ser Met Ala 320 Lys Gin Ile Gly Asn 325 Ala Vi. Pro Cys Glu 330 Leu Aa Arg Leu Phe Giy 335 Leu His Leu Ile Giu Asn Cys Thr Asn Lys Asp Ser 340 345 <210> 44 <211> 974 <212> PRT <213> Escherichia coli <400> 44 Met Leu Gly Arg Gin Gin lie Ala Gly Ile Pro Thr Ala Leu Ser Glu 1 5 10 Tyr Ala Asp 25 Leu Phe Lys Asn Ala His Asp Ala Lys Ile Phe Phe Arg Met Thr Thr Glu Asf Leu Leu Arg Asn Val Glu Val Asp Asp Asp Gly Leu Gly Thr Ile Gly Thr Ser Asp Giu Phe Ser Lys Glu 55 Asp Pro Glu Arg Trp Leu Leu Ile Asp Ala Ile Asn Ala Val Asp Asn Lys Ala Phe Ile Met Gly Gly Ile Gly Arg Leu Ser Ile Ala Arg Asp Asn 115 Leu Phe Ala Ala 100 Glu Gly Pro Gln Val 105 Val Val Leu Thr Leu Lys Pro Leu 120 Asp Ala Ala Phe Val 125 Glu Arg Ala Lys 110 Asn Trp Ser Ile Pro Ile lie Pro Ser 130 Arg Thr Leu 135 Glu Leu Asp Asp le Ile Asn Cys Phe Thr 145 Met Lys 155 Ser Thr Lev Asp Glu 160 Ile Giu Gin Ala 165 Val Asn Asn Leu Asp 170 Thr Leu Ser His Lys Ile 175 Ser Lys Ser Phe Asp Pro 195 Gly Asp Gly Lys 180 Ile Ser Gin Ile Asn 185 Lys Gln Leu Ser Leu Gly Gly Leu Trp Glu Lys 200 Phe Leu 205 Thr Ser Phe Glu 190 Arg Leu Ser Glu Glu Ile His Gly Thr 210 Leu Ile His 215 Thr Ile Ile Met Pro 220 Asp Asp Ile Ser Asp Ser 225 Ser Asn 235 Phe Lys Thr Ser Giu Gin 240 Thr Asn Thr Met Tyr 255 Ser Arg Leu Glu 245 A la Leu Leu Giy 250 Ser Asp Ser Asn Pro Pro Ile Ile Ala Arg Phe Arg Asp Tyr Leu Glu 260 265 270 Asp Gay lu Cys lie Asp Arg Ile Ser Glu Ser Ile Phe Phe Thr Pro 275 Phe Asn Leu Ala 280 His His Ile Glu 285 Trp Phe Asn Glu Gin Glu 290 Phe GlY Asp 295 Thr Giy 300 Giy Gin Phe Ser 305 His Giy 310 Trp Val Ser Val Tyr 315 Gin Glu Glu Pro Ile 320 His Val Vai Thr 325 Lys Lys Asn Asn Leu Thr Gln Cys Giy 335 Pro Phe Lys Arg Leu Pro 355 Tyr Gly Gly Ile 340 Met Leu Aia Tyr Ile 345 Pro Gly Arg Leu Giu Leu Trp Ala 360 Arg Leu Lys Glu Lys 365 Ile Arg Asp Ser 350 Thr Asp Arg Leu Pro Tyr Giy 385 Ser 370 Asp Ser Ala Ser Leu Tyr Ile Asp Thr Asp 390 Glu Tyr Phe Asp Gly Leu Leu Lys Ile Glu 395 Arg Arg 380 Lys Arg Arg Thr Leu 400 Phe Ser Tyr 405 Glu Arg 410 Leu Leu Phe Gly Ala Ile 415 Glu Leu Thr Giu Giy Phe 435 Glu Asn Phe 450 Aso Met Ser Lys 420 Ile Asn Asn Ala Ser 425 Tyr Val Giu Lys Glu Asn Lys Pro 440 Ala Lys Gin Phe Lys 445 Lys Ala Gly Arg 430 Glu Met Leu Asp Asp Giy Phe Ile Giu Glu Leu Phe 470 Leu Ser Lys Arg Asp Phe Phe 460 Arg Glu Thr Lys Gin 475 Arg Asn Glu Glu 480 Asp Leu Arg Ser Lys Gln 490 Phe Thr Lys Ala Lys Lys Asp 495 Asp Lys Leu Asp Asn Asp 510 Arg Leu Lys Tyr Trp Asn 515 Lys 500 Leu Tyr Asp Phe 505 Ile Giu Ile Asn Lys Leu Ile Asn Lys 520 Asn Giu Giu Tyr 525 Phe Ser Ser Thr Giu lie Thr Asp Thr Asn lie Asp Tyr Val Tyr Asn 530 535 540 Lys 545 Ile Lys Glu Gin Asn Asp Ala Ile Ile Lys Asn Leu Axg Asn Ser 550 555 560 Vai Asp Ile Lys Lys 565 Pro Ser Gly Val Gly 570 Leu Thr Lys Asn Leu Trp Leu Asn Glu 595 Asp 580 Arg Tyr Gin Ile Glu 585 Arg Gin Lys Ile Glu Leu Ser 575 Leu Leu Ser 590 Glu Leu Asp Leu Lys Asp Asn Val 600 Asp Ar; Lys Leu Ile 605 Asn Lys 610 Asn Asn Asp Phe Asn Leu Arg Lys Arg 620 Leu Glu Asp Ser Leu 625 Asn Leu Gin Gln Ser 630 Tyr Tyr Giu Lys Glu 635 Leu Thr Lys Leu Tyr 640 Asn Asp Ala Lys Ala Leu Lys Asp Gin Ser Lys Ala Asn Arg 655 Leu Ile Ser Sex Tyr Glu 675 Asp 660 Asn Lys Lys Lys His 665 Lys Ser Glu Leu Lys Asn Ile 670 Thr Ala Tyr Phe Gin Ser Thr Asn 680 Leu Asn Gly Lys Ile Leu 690 Asp Vai Lys Ar; Asn 695 Leu Glu Ser Lys Glu Arn Thr Ser Asn 705 Ile Glu Val Ile Asn 5cr Asp Ser Thr 725 Glu 710 Ile Arg Lys Leu Thr 715 Gin Ile Ala Thr Ser Glu Asn Leu 730 Ser Se: A.1a Gin Vai Thr 735 Glu Ala Ile Asn Ala Glu 755 Glu 740 Thr Giu Leu Glu His 745 Leu Ar; Asp Gln Gin Ala Asn 750 Val His His Leu Ile Leu Leu Gly 760 Met Ala Leu Ser Val 765 Giu Phe 770 Asn Gly Asn Ile Ala Ile Ar; Ser Ala 780 Leu Ar; Glu Leu Ala Trp Ala Asp Asn Pro Lys Leu Asp lie Ile Tyr Gin 795 Ile Arg Thr Ser Phe Asp His Leu Asp 805 Tyr Leu Lys Thr Phe Thr 815 Pro Leu Thr Ala Ile Leu 835 Arg 820 Arg Leu Ser Arg Ser 825 Asp Val 840 Lys Thr Asn le Thr Gly Thr 830 Leu Giu Lys Glu Phe Ile Arg Phe Asp Asp A.rg 845 Gu Gly 850 Ile Giu Leu Phe Thr Ser Lys Phe Val Asn Gin Giu Ile 860 Ile Asn Leu le Asp Val 865 Thr Tyr Thr Se: Thr 870 Ile Tyr Pro Val Phe 875 Asn Ala le Tyr Leu Gly Lys Thr Thr 890 Gly Giu Lys Ar; Leu Ile 895 Leu Asp Ala Thr 900 Glu Thr Gly Phe Ile Gly Asp Thr Gly Pro Gly 910 Phe Thr Arg Val Ser Thr Ar; Asp Arg Asp 915 Ile 920 Ile Phe Asp Met Gly 925 Lys Thr 930 Gly Gly Ar; Giy Met 935 Gly Leu Phe Ile Ser 940 Lys Glu Cys Leu Ser Arg Asp Giy Phe 945 Giy Ala Phe Phe Ile 965 Ile Ar; Leu Asp Tyr Thr Pro Glu Glu Thr Ser Glu Ile Glu Pro Ser Glu 970 <210> <211> 555 <212> PRT <213> Escherichia. coli (400> Met Thr Se: Se: Thr Asp Phe 1 5 Arg Phe Leu His Se: Vai Vai His Lys Leu Ser Giu Asp Cys Vai Arg 10 Ala Val Asp Asp Asn Met Ser Phe Gly 25 Ala Gay Ser Asp Thr Phe Pro Asp Glu Asp Ile Asn Ala Leu Val Asp Pro Asp Asp Asp Pro Thr 55 Pro Ile Ile Thr Ala Ser Ala Ser Pro Arg lie Glu Ser Thr Lys 70 Ser Lys Ala Lys Val Lys Asn His Pro Asp Tyr Gin Ala Ala Glu Ala Phe Lys Asp Gly Ile Ala Cys Cys Gly Leu Thr Ala Ser 115 Leu 100 Ala Lys Se: Phe Asn 105 Val Giu Glu Arg Asp Ile Ile 110 Se: His Lys Ala Ile Thr lie Leu Trp Asp Met Gln Ser 130 Asp Ser Gay GIn Phe 135 Ala Ile Giu Ile Ile 140 Lys Ser Ile Ile Val 145 Thr Ser Asp Ile Asn Giy Glu His Val 165 Gly Gay Arg Leu Arg 155 Leu Leu Ser Ile Tyr 160 Thr Ala Val Ile Thr 170 Lys Leu Asn Asn Giu Leu 175 Lys Lys Thr Glu Asp Asn 195 Tyr 180 Arg Ser Val le Asn Asp Asp Se: Ile Phe Ile 190 Ile Ser Lys Tyr Ala Leu Glu Gln 200 Trp Cys Ile Val Val 205 Asp Val 210 Tyr Giu Lys Asp Leu 215 Pro Asn Val Leu Ile 220 Lys Lys Phe Thr Leu Thr Ala Gly Leu 230 Leu Se: Asn Ala Ala 235 Leu Ser Cys Ile Se: 240 Giu Ile Arg Giu Leu Asp Thr Ala 260 Glu Se: Arg Ala 275 Lys 245 Thr His Gay Ile Leu 250 Thr Lys Tyr Asn Asn Lys 255 Tyr Val Ser His Ile 265 Leu Asn Leu Ile Lys Se: Lys 270 Ala Val Asp Tyr Ala Tyr Glu Asn Ala His Asp Tyr 285 Leu Ile Ser Giu Glu Ile Arg Ser Ile Leu Gln lie Ser Giu Asn Leu 290 Lys Asn 300 Trp Lys 305 Tyr Ser Leu Sex Lys 310 Cys Ser Leu Ser Pro Ile Phe His 320 Ala Lys Asn Lys Asn Phe Leu 330 Asn Thr Gly Lys Lys Gin 335 Lys Asp Leu Leu Glu Glu 355 Glu Tyr Leu Glu His Leu Ar; 345 G.1 Ile Leu Ser Gln His Ala His Ala Ser Leu 365 Leu Ala Asp Ser 350 Gly Lys Lys Met Gin Leu Ser Gin Asp 370 Ser Gby 375 Arg Glu Asp Lys Lys 380 Tyr cys 385 Asp Leu Glu Ile Arg Ser Leu His Ser His Ile 400 Asn Val Ser Gin Gly Thr Leu 410 Cys Leu Asp Ala Tyr Asn 415 Phe Val Tyr Glu Lys Ala 435 Tyr Asn Leo leu 420 Asp Ile Gin Pro Leu 425 Ar; Asp Ser Val Phe Leu Phe Leu 440 lu Gly Thr Leu Asp 445 Tyr Arg Leu His 430 Asp Asn Asn Lys Ile Lys Leu Ile Glu Tyr Gly Gly 450 Met Pro Phe 460 Sex Ala Lys Ala 465 Asn Ser 470 Ile Ile le Se: Phe 475 Asn Phe Gly Val Glu 480 Gly Asn Gly Ile Giy Lys Lys 490 Val Asn Leu Val Asn Thr 495 Asp Tyr Ile Lys Val leu 515 Ile Thr Thr 530 Val Pro Leu Leu 505 Ile Glu Lys Ile Trp Ile Gly Glu 520 Asn Lys Thr Thr Tyr 525 Giy Se: Thr Pro 510 Ala Gin Lys Leu Asp Gln Asp Ile Val Ala 535 leu Ser Ar; Ile 540 His Glu Trp Leu Arg Ile Lys Ser Lys Asp Ile 545 550 555 <210> 46 <211> 82, <212> PRT <213> Escherichia coli <400> 46 Met 5cr Sex Arg Gin Ile Leu Giu His Tyr Asn Ala Leu Thr Tyr Pro 1 5 10 Leu His Gin Val Cys Thr Se: Ile Leu Leu Gin Met Thr 5cr Asn Leu Leu 5cr Ser Trp Gly Lys Se: Ile Tyr 40 Glu Asp Ile Ser Gi y Asn Ile Ile His Phe Asn Phe Se: Tyr Cys 70 Ile 55 Pro Leu Pro Ile 5cr Arg Ala.Arg Leu Scr Ile Val Arg Ile Lys Trp Met Ser Met Asp s0 Tyr Met <210> 47 <211> 98 <212> PRT <213> Escherichia coi <400> 47 Met 5cr Ile Ile Phe 1 5 Asn Gly His Tyr Arg 10 Met Lys His Arg Thr Trp Ile Thr Giu Val Val Gly Leu Arg Leu His Phe Giu Giu His Leu~ Pro GIn Val Arg Arg Leu Gly Val 40 Pro Lys Se: Thr Ala cys Giy Met Phe Val Arg Phe Arg Lys Al a Gly Phe Ser Trp Leu Pro Ala Gly Met .Ser Giu Arg Giu Leu Asp Gly Arg Leu Tyr Gly Sc: Thr Ser Thr Val Pro Val Val Leu Cys Ser Gly Ser Val Ile Gin Asp Thr Ser Lys 90 Se: Cys <210> 48 <22.1> 106 <212> PRT <213> zscherichia coli <400> 48 Met Ile Lys Thr Arg 1 5 A.rg Thr Lys ALrg 1hr 10 Phe Ser Pro Glu Phe Lys is Leu Giu Ala Giu Val Ala Giu Gin Val Vali Lys Tyr Gin Arg Asp Val Arg Arg Lys Trp Gin Ala Leu Giu Asn Pro Asp His ILeu Ile Arg Leu Tyr Lys Gin Leu Gin Gly Ile Pro Ala Gly Asn Ala Ile Thr Pro Giu Gin 170 Axg Giu Ile Gin Gin Leu Lys Ala Gin Lys Arg9 Val Glu Met Glu Lys Glu Ile Leu 90 Lys Gin Ala Ala Val Leu Met Ser Glu Pro GJly Lys Leu Ser Arg 105 <210> 49 <211> 27 <212> DNA <213> Ar-tificial Sequence <220> <223> Description of Artificial Sequence: Oiigonucieotide <400> 49 tgctctagag ccattactca qaatggg <210> <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> cgcgagctcg acgactgaat gatccc 26 <210> 51 <211> 26 <212> DNA <213> Artificial Sequence <22 0> <223> Description of Artificial Sequence:oligonucleotide <400> 51 tcccccgggt actgcagcac tcaacc 26 <210> 52 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:COzigonuclectide <400> 52 gatcccggga ccactgaaat gcgtgc 26 <210> 53 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:oligonucleotide <400> 53 tcgtctagag atgatggtga tggagca 2*7 <210> 54 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequenlce:OCligoflucleotide <400> 54 gaactqcagc caaatactga taccaccc 28 <210> <211> 21 <212> DNA <213> Artificial sequence <220> <223> Description of Artificial Seauence:Oligonucleotide <400> gaactgcagg ctaaaacaga agacgcg 27 <210> 56 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:oligoriucleotide <400> 56 catgcatgca ctccatatga caaccgc 27 <210> 57 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 57 tcgtctagaa tgaagctgcg catgagg 27 <210> 58 <211> 27 <21~2> DNA <213> Artifci.al Sequence <220> <223> Description of Artificial Secruence:oligoflucleotide <400> 58 caactgcagt cgcaaattoc gaactgg 27 <210> 59 <211> 27 <212> DNA <213> Art;ificial Sequence <220> <223> Description of Artificial Sequence: Cligonucleotide <400> 59 caactgCaga ccgcaacttt tcgacgc 27 <210> <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligolucleotide <400> catgcatgcc agtgagccat tgttccc 27 <210> 61 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 61 tgctciagat acgactctga caggagg 27 100 <210> 62 <211> 26 <212> DNA <213> Artificial Sequence <220O> <223> Description of Artificial Sequence: Oligonucleoiide <400> 62 tcagatatca actaccagca gtttgg 26 <210> 63 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> 63 tcagatatcc ataaagagtg acgtggc 27 <210> 64 <211> 27 <212> DNA <213> Axtilicial Sequence <220> <223> Description of Axti.ficial Sequence: Oligonucleotide <400> 64 tgctctagaa aacgtggcaa cagagog 27 <210> <211.> 26 <212> DNA <213> Ar-tificial Seauence <220> <223> Description of Artificial Sequence:OCligonucleoiide <400> tgctctagaa ggcgttgtcg atcctg 26 <210> 66 (211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 66 gaactcagg aaaaggccga gcagaCtg 28 <210> 67 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> 67 gaactgcagt acagccatgt ttacggt 27 <210> 68 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Aitificial Sequence:Oligonucleotide <400> 68 catgcatgcg gtgtacgaca gtttgcg 2 <210> 69 <211> 26 <222> DNA (223> Artificial Sequence <220> <223> DescriptiOn of Artificial sequence:oligonucleotide <400> 69 tgctctagac acatcatggg cacacc 26 <210> <211> 27 <212> DNA <213> Artificial Sequence <22 0> <223> Descri~ptionl of Artificial Sequence: oligonucleoiide <400> 70 2 gaactgcaga accgtccaca tcaggcg 2 <210> 1 <211> 27 <212> DNA <213> Artif icial Sequence <22 0> <223> Description of Artificial Sequence: oligofulUeloiide <400> 71 gaactgcaqa ccctgcttgc cattceg 27 <210> 72 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:0ligonucleotide <400> 72 catgcatgea taagcgtcga acaggcg 27