AU2007200542A1 - Virulence genes and proteins, and their use - Google Patents

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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: 1 VIRULENCE GENES AND PROTEINS, AND THEIR USE O Field of the Invention oo This invention relates to the identification of virulence genes and proteins, and their use. More particularly, it relates to their use in therapy and S 5 in screening for drugs.

IBackground to the Invention 0E. coli is a member of the Enterobacteriaceae, or enteric bacteria, which are Gram-negative microorganisms that populate the intestinal tracts of O animals. Other members of this bacterial family include Enterobacter, 0o Klebsiella, Salmonella, Shigella and Yersinia. Although E. coli 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. coli 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. coli 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 SA 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 00 in vivo to exert a therapeutic effect A peptide according to the present invention may comprise any of the C 5 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.

S -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.

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

Ca peptide or protein that may have a role in the maintenance of pathogenic 0 bacteria. In particular, a virulence determinant is a bacterial protein or peptide that is implicated in the pathogenicity of the infectious or disease-causing C 5 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 0 reduction in the pathogenicity of the microorganism.

Signature-tagged mutagenesishas 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 2 o 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 Tn10. 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 4 ~transposon insertion is identified by isolating the DNA flanking the transposons T. insertion site, and this permits characterisation of the genes implicated in o0 virulence.

Once an avirulent microorganism has been identified, it is possible to c 5 determine more fully the potential role of the mutated gene in virulence, by I 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 io 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 c-I chromosome, suggesting that they were acquired by horizontal transmission from another organism. For example the G+C content of the E. coli K12 0 genome is 52%. Any pathogenicity islands found in E. coli strains are likely to have a G+C content that varies from this average.

NI 5 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 Stypically at least 30%, preferably at least 50%, 60% or 70%, and more io 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 6 nature/severity of the condition to be treated, the type or health of the subject Cetc.

00 SThe following Examples illustrate the invention. For the Examples, STM was used to screen an E. coli K1 mini-Tn5 mutant bank for attenuated mutants, S 5 using a mouse model of systemic infection. The basic procedure followed that O disclosed in Hensel et al, supra. E. coli K1 containing a mini-Tn5 insertion C within a virulence gene was not recovered from mice inoculated with a mixed Spopulation of mutants, and is therefore likely to be attenuated.

c-i 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. coli 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. coli 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. coli 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 7 c- D Immunity, 1983; Vol. 39:315-335), and shown to be attenuated with a competitive index (CI) of 0.38. This confirms that the attenuation of the original Stransposon 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 CI 5 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 SmdoG and the entire pUC1 9 sequence was then amplified by inverse PCR with the oligonucleotides 5'-TCCCCCGGGTACTGCAGCACTCAACC-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 allelic transfer after conjugation of the pCDV442 constructs into wild type E. coli 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.

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

00 As the E. coli K12 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 c 5 presumed E. coli K1 creD gene.

SExample 3 SA 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 SSEQ ID NO. 7.

The nucleotide sequence shows 93.7% identity to the recG gene of E.

coliK12, 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. coliKI 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.

coli 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 attenuated with a competitive index of 0.43.

Example 9 Several mutants were also found with a transposon insertion within the T. same region. Cloning and sequencing the region revealed a nucleotide 0O sequence shown as SEQ ID NO. 10. This sequence has homology with the tatABCD operon of E. coli K12 (EMBL and Genbank accession numbers cN 5 AJ005830, AE000459 and AE000167). This operon encodes proteins of VD predicted mass 9.6 kD, 18.4 kD, 28.9 kD and 29.5 kD, which function as Scomponents of a Sec-independent protein export pathway. The pathway permits translocation of fully folded proteins to the periplasm through a gated Spore, 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. coli 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 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) 00 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. GCA TGC ACT CCA TAT GAC AAC CGC-3' (SEQ ID NO. 56) t- 0Primers SEQ ID NO. 53 and SEQ ID NO. 54 were used to amplify DNA N sequences upstream of tatA, 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) 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.

11 SAfter cloning these flanking DNA fragments into pUC19, a non-polar C aphTkanamycin resistance cassette (Galan et al, J.Bacteriol, 1992; 174:4338- 0 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 q n chromosomal copies of the E. coli K1 tatA, tatD and tatE genes were then Smutated by allelic transfer after conjugation of the pCVD442 constructs into wild Stype E. coli K1.

SDisruptions 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. typhimurium 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) S12 Primers SEQ ID NO. 65 and SEQ ID NO. 66 were used to amplify DNA C sequences downstream of the S. typhimurium tatC gene, Primers SEQ ID NO.

00 67 and SEQ ID NO. 68 were used to amplify DNA sequences upstream of the S. typhimurium tatC gene.

c 5 The encoded amino acid sequences for two regions of the tatC gene are n shown as SEQ ID NO. 18 and SEQ ID NO. 19.

0 After cloning these flanking DNA fragments into pUC19, a non-polar kanamycin resistance cassette (aphT) was inserted between the flanking DNA 0 fragments to replace the S. typhimurium tatC gene. This DNA fragment was 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: S13 5'-TGCTCTAGACACATCATGGGCACACC-3' (SEQ ID NO. 69) 5'-GAACTGCAGAACCGTCCACATCAGGCG-3' (SEQ ID NO. 00

O

5'-GAACTGCAGACCCTGCTTGCCATTCCG-3' (SEQ ID NO. 71) 5'-GAACTGCAGACCCTGTGCGCCATTCCG-3' (SEQ ID NO. 72) O Cloning of the DNA fragments and the aphT kanamycin resistance 10 cassette into pUC19 followed the procedure outlined above for S. typhimurium.

O 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 secuence homology to several Group 1 glycosyltransferases from a number of bacteria. Sequence homology was also shown to the gnd gene of E. coil K12 (at nucleotides 4197-4604 of SEQ ID NO. 22).

The translation of the E. coil eckl gene is shown as SEQ ID NO. 26.

The gene has been tested for attenuation of virulence, as described above, and 3 0 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 0 14

O

Sserotype 0111 (TrEMBL database accession number AAD46732). The amino acid sequence also shows homology with the eckl protein from E. coli K1 and 00 also the TrsE protein from Yersinia entercolitica (TrEMBL database accession

O

number Q56917).

C 5 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 O putative glycosyl transferase TrsC from Yersinia entercolitica (TrRMBL database accession number Q56915), and also the glycosyl transferase WbnA Sfrom 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.

D Testing the genes in a model for attenuation of virulence, as described c above, showed that the iroD gene was attenuated with a competitive index of S0.107. 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 N 5 attenuated in virulence with a competitive index of 0.1. This indicates that the n attenuated phenotype is linked to the insertion within iroD. However, it is S- possible that the attenuation is due to a polar effect on the E. coli K1 iroE gene.

Example 9 SA 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 as/A /hemY region of E. coli K12 (EMBL accession number AE000456). The asIA encodes an arylsulfatase homologue whereas hemY is involved in the biosynthesis of protoheme IX. This demonstrates that the disrupted region is at least partially identical to the asIA /hemY region of E. coi: 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 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, 16 c such as a regulatory RNA similar to oxyS (Altuvia et al., Cell, 1997;90:43-53), L encoded within this region. Alternatively the transposon could be disrupting oo some DNA structure that may, for example, be involved in DNA replication.

O

This DNA region is also present in the pathogen Salmonella typhimurium c 5 suggesting that it may be important for pathogenicity in other organisms. This I region (SEQ ID NO. 33) may be used as a target, to identify anti-microbial 0drugs.

Example O 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. coli 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. coli K1 mtd2 gene was tested for attenuation of virulence, as 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 (12)

1. An isolated peptide encoded by any of the genes identified herein as creC, recG, yggN, eckl, iroD, iroC, iroE, mtd2 and ms1 to 16, obtainable from E. coli K1, or a 00 homologue thereof in a Gram-negative bacterium, having at least 30% 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 any of the amino acid sequences Sidentified herein as SEQ ID NOS 5, 7, 9, 23, 24, 25, 26, 28, 29, 31, 32 and 35-48.

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 within 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 any of creC, recG, yggN, eckl, iroD, iroC, iroE, mtd2 and ms1 to 16, obtainable from E. coli 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. coli. SEQUENCE LISTING <110> microscience Limited <120> VIRULENCE GENES AND PROTEINS, AND THEIR USE <130> REP05921WO <140> <141> <160> 72 <170> Patentln Ver. 2.1 <210> 1 <211> 4333 <212> DNA <213> Escherichia coli <220> <221> CDS <222> (101 <400> 1 ccattactca atgccgaggc tcagaatttt accactaaca ttgtcataca ataaattgcg acacgtactt cc gga ta ta a agccataatg atatgaaaag cgttgcgcgg tgtcggtta 7) (2549) gaatgggcgg acaaaaaaat ctaaattatt ccagtaaaaa atgacagtcc gcaatgtcag tccaccattt cgaaaaatac acggttcggc ggatccctaa gtactgggtt tgcctttagg atacacaata caccgatagt tctgatacgt ccacaggtgt aggccaactt tagggggatg tttcaaggga ctgcatgcgg gctattcaca caacatcagc catata tggt cttgttgcca aaaattgttc tttaccatcg ttgaatatcc gatattaatt tccgctttcc gctgttaaca tagcgtaaaa aacgagtgga tgccatgtat caggcgcgga taactaatct tagcgacacc ttcttattac agaatttttt agacgcacag cccaggccaa ctttgacgta tcgggatacc aaagcatgta tgaagtcatt ggctcgaata tggagtcgag cggatttttc gacctgaccg cgcataaccg attcgtttta cgtcgicatg cgtattatat ttgcagcata tacacgttcg ggaaaagtac aaaaagggtc gattaaagaa gaaatattca gtcttatccc cgccaggcgc aggcttcaag gtttttatgc atagcatcat cgctaccact aaccagaatg gaagegtctg 780 taagaeggtt gataaataaa tttgctggca aaccctacac gaagtcgatg cttctgtctt 840 taggagaagc acggaaagtg aaaacggttg caatcaggtg cttaatccat gagccagtgt 900 gctgaacgat accgggattc tgitgtcgga aiggcaggtt atccatiaaa atagatcgga 960 tcgatataag cacacaaagg gggaagtgct tactaatiat gaaacataaa ctacaa atg 1019 Met atg aaa aig Met Lys Met tct. tea age Ser Ser Ser tgg ttg agt get Trp Leu Ser Ala gia atg tta acc Val Met Leu Thr cig tat aca Leu Tyr Thr caa gct caa Gin Al1a Gin 10 67 1115 tgg gct itc agt Trp Ala Phe Ser att Ile 25 gat gat gtc gca Asp Asp Val Ala aag Lys tec tia Ser Leu gcc ggg aaa ggc Ala Gly Lys Gly gag gcg ccc aaa Glu Ala Pro Lys aac ttg ccc icc Asn Leu Pro Ser gtt Val ttc cgc gat atg Phe Arg Asp Met aaa Lys 55 tac geg gac tat Tyr Ala Asp Tyr cag Gin cag ate cag tti Gin Ile Gin Phe 1163 1211 1259 cat gac aaa gcg His Asp Lys Ala tac Tyr tgg aac aai cig Trp, Asn Asn Leu ace cea. ttc aaa Thr Pro Phe Lys cte gag Leu Giu tic tae cat Phe Tyr His gtg act gce: Val Thr Ala 100 ggi aig tac tic Giy Met Tyr Phe gat Asp ace ecg gte Thr Pro Val ace gca gic aaa Thr Ala Val Lys ega Arg 105 ate aaa tac age Ile Lys Tyr Ser aaa ata aat gaa Lys Ile Asn Giu cog gat tat tic Pro Asp Tyr Phe 110 aaa gac cii ggi Lys Asp Leu Gly 1307 1355 act tic Thr Phe 115 itt gee Phe Ala 130^ gge gat git cag Giy Asp Val Gin ggt tic aaa gig Gly Phe Lys Val 135 cat His 120 gac aaa gac aeg Asp Lys Asp Thr gta. Val 125 1403 1451 cit tac Leu Tyr ccg ate aac Pro Ile Asn 140 age aaa gat aaa, Se: Lys Asp Lys gat gaa aic gtc agc atg ctc ggg gcc agc tat tic cgc gtg att ggt 19 1499 Asp Giu Ile Val Ser Met Leu Gly Ala Ser Tyr Phe Arg Val Ile Gly 160 gca ggt cag Ala Gly Gin gcc tig cca Al1a Leu Pro 180 tat ggc cit tct. gca Tyr Giy Leu Ser Ala 170 cgc ggc ctg gca ait gat acc Arg Giy Leu Ala Ile Asp Thr 175 1547 tcg ggt gaa. gaa Ser Gly Giu Giu cca cgc tic aaa Pro Arg Phe Lys gag Gi u 190 tic tgg aic Phe Trp Ile 1595 gag cgt Giu Arg 195 cca aaa ccg act Pro Lys Pro Thr gat Asp 200 aaa cgt tta acc Lys Arg Leu Thr tat gca tig ctt Tyr Ala Leu Leu gac Asp 210 tcg ccg cgc gcg Se: Pro Arg Ala ggi gct tac aaa Gly Ala Tyr Lys ttc Phe 220 gia git aig cca Val Val Met Pro gga Gi y 225 1643 1691 1739 1787 cgt gac acg gt Arg Asp Thr Vai gtg gat gig cag tcg Val Asp Vai Gin Ser 230 ggg git gca ccg tta Giy Val Ala Pro Leu 250 aaa, Lys 235 aic tat cig cgc Ile Tyr Leu Arg gat aaa, Asp Lys 240 tit ggg Phe Giy gic ggc aaa, Val Gly Lys ccg aac caa. Pro Asn Gin 260 ctg Leu 245 acc agt aig tic Thr Ser Met Phe ctg Leu 255 ccg tcg cci gca Pro Ser Pro Al1a a at Asn 265 aac tat cgi ccg Asn Tyr Arg Pro tig cac gac Leu His Asp 1835 ict aac Se: Asn 275 ggt cig tct atc Giy Leu Ser Ile gci. ggt aat ggc Ala Giy Asn Giy tgg atc tgg cgi Trp Ile Trp Arg Ccg Pro 290 tig aat aac ccg Leu Asri Asn Pro cat ita gcg gic His Leu Ala Val a gc S er 300 agc tic icg aig Ser Phe Ser Met gaa Giu 305 1883 1931 1979 aac ccg caa. ggc Asn Pro Gin Gly tc Phe 310 ggt cta. ttg cag Gly Leu Leu Gin cgt Axg 315 ggi cgt gat tic icc cgc Giy Arg Asp Phe Se: Arg 320 ttt gaa gat Phe Giu Asp ctc gat gat cgi Leu Asp Asp Arg 325 tac gat Tyr Asp 330 ctt cgt cca agc Leu Arg Pro Ser gca tgg gig Ala Trp Vai 335 2027 act ccg aaa Thr Pro Lys 340 ggg gag tgg ggc Gly Giu Trp Gly aaa Lys 345 ggc agc gtt gag Giy Ser Val GlU cig gig gaa at Leu Val Giu Ile 350 tac tgg acg ccg Tyr Trp Thr Pro 2 07 cca ace Pro Thr 355 aac gat gaa acc Asn Asp Glu Thr aac Asn 360 gat aac atc gic Asp Asn Ile Val gct Al a 365 cag ctg ccg gag Gin Leu Pro Glu ggt aaa gag atg Gly Lys Glu Met aac Asn 380 itt aaa tac acc Phe Lys Tyr Thr 2123 2171 2219 acc tic agc cgi. Thr Phe Ser Arg gaa gac aaa cig Glu Asp Lys Leu cat His 395 gcg cca gat aac Ala Pro Asp Asn gca tgg Ala Trp 400 gig caa caa Val Gin Gin ait cgc cag Ile Arg Gin 420 acg cgt cgi ica acg ggg Thr Axrg Arg Ser Thr Gly 405 410 gat gig aag cag Asp Vai Lys Gin tcg aac cig Ser Asn Leu 415 iii acc ggc Phe Thr Giy 2267 2315 cci gac ggi act Pro Asp Giy Thr ate Ile 425 gee iii gig gic Ala Phe Val Vai gci gag Ala Giu 435 agc att Ser Ile 450 aig aaa aaa. Met Lys Lys ggt gat aat Gly Asp Asn ctg Leu cca Pro 440 gag gat ace ccg Glu Asp Thr Pro gic aca geg caa Val Thr Ala Gin 445 acg gig cgt tat Thr Val AXrg Tyr a cc Thr aac Asn 465 ggi gag ata git gaa Gly Glu Ile Val Giu 455 igg cgi cig gig atg Trp Arg Leu Val Met 475 agc Ser 460 ccg git acc aaa Pro Val. Thr Lys ggc Gly 470 cgt gig aaa gig Axg Val Lys Vai aaa gat Lys Asp 480 gat cag Asp Gin 2363 2411 2459 2507 2549 gcc aag aaa Ala Lys Lys acg ttg agt Thr Leu Ser 500 act gaa aig cgi Thr Glu Met Arg gct Ala 490 gcg cig gig Ala Leu Val aai gcc Asn Ala 495 aat gaa Asn Giu 510 gaa ace igg agc Glu Thr Trp Ser tac T yr 505 cag ita cci gce Gin Leu Pro Ala taagacaact gagiacatig acgcaatgeC catcgccgca agcgagaaag cggcattgcc 2609 gaagaci~gat atccgcgccg iicatcaggc geiggaigee gaacaccgca ccigggcgeg 2669 ggaggatgac acttgctgat agaagtaaaa cigggat~cgC agagcaggag gatcctgacg tcaggggtgg tatgcagctt ctgttgggtg gtcgcgataa atcgcaeggc tgcgtgcaac ttcttagtga ttatcgctga agcgtaaaag tggiggtgct tgatggaagc atacgctgta ccggtttgca gcgtgaaacc ccggttcaat gggtctggat atgagctaaa tggtgaaggg tccccgcaag ggacagttaa cgctcctcga cigcgtggac agtgagcaaa ctcgcgcaaa gcgctgatta ctgccttata tccgccggat atacagtata gttgatcatg gtgggaatca cagttataac agtcggtggc cggtaatatc ggatgctgac caacccgaac tgcgcgctgt cttctggcaa gtttatcgag cctgtcacat tgcttacgat acgtgaccgc tatgcacccg gctcggtaaa ttaaagacga tgtttcccga gcgatgtgac agtggcgtac ctgttgtcgc atcctatgga tgctgcaaac tctggaccgg tctgcgtcaa cctatctgta gtaaaagcca ccggatatct gaaggtcaga gatgacttct tcggtaatga gccgggatca cagcagttcg cttggcgagt cactgtgcac gacttcgtgg ctcccgggtt cgctggtgcc gttcaccgtg ggcgcgtcig cgaagggcgc cccgtggcgt gccgcgctat cgtcggtacc gacctggtat tatggttggt cggtatcctg cgttgatggg cagttggcga aegaagacgt ccgggaatgc gcgtcgcaga ttttctatcg gccgtcgctg ccggtgatig ticagtcgtc cgacccgcgt cgcactactg tggciccgct aagcggcgtt cttatgaaga acggtaacct cggtgttcct gaacaagcct gatcagctaa accaacccgg ctggctcgtt atccgccgtt atgaagacca caggatgtgt atcctctttg cttcctgcaa tgaaccatta gaaccgtgtt caaacatttt gcaaaaagcc ccgccgccgc gggcagccag tttgtgcggc gccgaaagcg gtatgggcca ggggcataac gccgggcgaa gatgcgccgt attaccgcct gatgaacttc gacgggcgtg ggccagattc aggcgatgcc taggccgttt tgaccaaaga acattctgtt ticttcctta gggtticctt cggtactgtt ctgcttattg aacccggagc tttgctggct gatgtctaca iggatggage cgtcgcgtga tacagctaca ctggtgcgcc tccggcatgg ctgtttacag gcgattatcc ggtictttig gcaggttggg aacttgcttg cgtctgttcc atgtcttatc 272 9 278 9 2849 2909 2969 3029 3089 3149 3209 3269 3329 3389 3449 3509 3569 3629 3689 3*?49 3809 3869 3929 3989 4049 4109 tctccgctcc gctgtggttt atgttcctcg cgctctctac tgcattgcag gtagiacatg 4169 cgttgaccga accgcaatac ttccigcaac cacggcagtt gttcccggta tggccgcagt 4229 ggcgtcctga gctggcgatt gcactttttg cttcgaccat ggtgctgttg ttcctgccga 4289 agctattgag cattttgctt atctggtgca aaggaacgaa agaa 4333 <210> 2 <211> 511 <212> PRT <213> Escherichia coli <400> 2 Met 1 Thr Met Lys Met Arg Trp, Leu Ser Al1a 5 Al1 a 10 Asp Val Met Leu Thr Leu Tyr Ser Ser Ser Trp Ala Phe Ser Asp Val Ala Gin Ser Leu Ser Val Phe Ala Gly Lys Gly Tyr 40 Tyr Ala Pro Lys Ser Gin Lys Gin Ala Asn Leu Pro Ile Gin Phe AXrg Asp Met Asn His Lys Trp Ala Asp Tyr Asp Lys Ala Glu Tyr 70 Gi y Asn Asn Leu Lys Pro Phe Lys Phe Tyr His Gin Thr Met Tyr Phe Asp 90 Ile Thr Pro Val Lys Ile Asn Lys Tyr Ser Pro Asp Tyr Giu Val Thr Phe Thr Phe 115 Giv Phe Ala Ala Val Lys Arg 105 Asp Asp Val Gin Lys Asp Thr Val 125 S er 110 Lys Asp Leu Lys Asp Lys Gly Phe Lys 130 Asn Asp Val 135 Met Tyr Pro Ile Giu Ile Val 145 Ser 150 Leu Gly Ala Ser 155 Phe Arg Vai Ile 160 Gly Ala Gly Gin Val Tyr Gly Leu Ser Ala Axrg Gay Leu Ala Ile Asp 170 175 Thr Ala Leu Ile Glu Arg 195 Ser Gly Giu Glu Pro Arg Phe Lys Glu Phe Trp 190 Tyr Ala Leu Pro Lys Pro Thr Asp 200 Lys Arg Leu Thr le 205 Leu Asp 210 Ser Pro Arg Ala Gly Ala Tyr Lys Val Val Met Pro Giy 225 Arg Asp Thr Val Val 230 Asp Val Gln Ser Ile Tyr Leu Arg Asp 240 Lys Val Gly Lys Gly Val Ala Pro Thr Ser Met Phe Leu Phe 255 Gly Pro Asn Asp Ser Asn 275 Gln 260 Pro Ser Pro Ala Asn 265 Asn Tyr Arg Pro Giu Leu His 270 Trp Ile Trp Gly Leu Ser Ile Ala Gly Asn Gly Glu 285 Arg Pro 290 Leu Asn Asr Pro Lys 295 His Leu Ala Val Ser 300 Ser Phe Ser Met Glu 305 Asn Pro Gin Gly Gly Leu Leu Gln Gly Arg Asp Phe Ser 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 Gly Ser Val Glu Leu Vai Glu 350 Tyr Trp Thr Ile Pro rhr Asn Asp Giu Thr 355 Asp Asn Ile Val Ala 365 Pro Asp 370 Gin Leu Pro Glu Pro 375 Gly Lys Giu Met Phe Lys Tyr Thr Thr Phe Ser Arg Asp 390 Glu Asp Lys Leu His 395 Ala Pro Asp Asn Ala 400 Trp Val Gin Gin Thr 405 Arg Arg Ser Thr Gly 410 Asp Vai Lys Gin Ser Asn 415 Leu Ile Arg Gin Pro ASp Giy Thr 420 Ala Phe Val Val Asp Phe Thr 430 Gly Ala Glu 435 Met Lys Lys Leu Giu Asp Thr Pro Val 445 Thr Ala Gin Thr Ser 450 Ile Gly Asp Asri Gi y 455 Glu Ile Val Glu Ser 460 Thr Val Arg Tyr Pro Val Thr Lys Gi y 470 Trp Arg Leu Val Arg Val Lys Val Asp Ala Lys Lys Thr 485 Thr Glu Met Arg Ala Leu Val Asn Ala Asp 495 Gin Thr Leu Ser 500 Giu Thr Trp Ser Gin Leu Pro Ala Asn Glu 510 <210> 3 <211> 574 <212> DN'A <213> Escherichia. coli <400> 3 ttcgttgatc accaaacgct tgataccgat cgcggtgttt cgccagcaag gccagagaag ccgtctgcat cgaagggata acgtagttgc ttgcaagatt ctgtcaccgt ggaaactgt cggttccttg aacccgtcat gtgctggaaa ctgaatcgcg ttccgcgtct aagctcaatc ctgatgcgct ttgtaggtcg ttgttcggtt ccctgatccc agatgaatcg ttaacgctct tcgcccgtga atcgtcgcct ggaattcccc cactggcatt acgcttatca. gataaggcgt atttccagcc ggaagagtat tcaatgctcc ggcaaccgca ccgccacgtt ggtgctgcta. ggagagatat gcgtaaaccg ggcctacaic tca c gtgccaccgt tcaccgccgc ctigatgatg aiggcgaccg gaacaggcgc agcgaiccgg tcttcatggg gatgcggctt gttccig ca a tggtctgcga aggtgctggt gttttatgca. cgcgtcaccg tgaacgagac tgacgatggc tgagtiatta cgcaataaaa tttattgatt 120 180 240 300 360 420 480 540 574 <210> 4 <211> 1478 <212> DNA <213> Escherichia coli <220> <221> CDS <222> (25) (1449) <400> 4 gggataatgc ctgaggggcc tgta atg Met cgt atc gge atg cgg ttg ttg ctg Arg Ile Gly Met Arg Leu Leu Leu 1 gge Gi y tat itt tia ctg Tyr Phe Leu Leu geg gtg gcg Ala Val Ala gec tgg Al1a T rp 20 cga aga Arg Arg 35 tte gta ctg get Phe Val Leu Ala att Ile tit gic aaa gaa Phe Vai Lys Glu gti Val aaa ccg ggc gig Lys Pro Gly Val gca acc gag Ala Thr Glu ggg acg Gay Thr ita atc gac Leu Ile Asp etc tet ggg Leu Ser Gly ac Thr gca acg ttg cig Ala Thr Leu Leu gag ctg gcg cgi Glu Leu Ala Arg ccc gat ttg Pro Asp Leu iii aat cag Phe Asn Gin 195 243 gac cca acg cai Asp Pro Thr His ggg Gi y eaa ctg gcg cag Gin Leu Ala Gin cia caa Leu Gin cai cgc ccg iii His Arg Pro Ph. gcc aai atc ggt Ala Asn Ile Gly 9gC Gi y ait aac aaa gig Ile Asn Lys Val cgc Arg aac gaa tat cat Asn Glu Tyr His gte Val 95 tat atg acc gat Tyr Met Thr Asp cag ggc aaa gta, Gin Gly Lys Vai tig Leu 105 tic gat tog gca Phe Asp Ser Ala aat Asn 110 aaa gcc git gga Lys Ala Val Gly ca g Gin 115 gat tat tcg cgc Asp Tyr Ser Arg tgg aat Trp Asn 120 gac gic igg Asp Val Trp caa aat cci Gin Asn Pro 140 cia Leu 125 acg tig cgt ggt Thr Leu Arg Gly cag tat ggt gcg cgc agc acg ttg Gin Tyr Gay Ala Arg 5cr Thr Leu 130 135 goc gat ccc gaa Ala Asp Pro Giu agt. Ser 145 tot gig atg tat Ser Val Met Tyr gt Val ISO gc gog ccg Ala Ala Pro ait atg Ile Met 155 gao ggc tog egg Asp Gly Ser Arg ati ggc git tig Ile Gly Val Leu gta. ggc aaa cog Val Gly Lys Pro aac Asn 170 gcg gcg aig got Ala Ala Met Ala cog Pro 175 gtc ati aag cgt Val Ile Lys Arg ago Ser 180 gag ogg oga. at Giu Arg Arg Ile ta Leu 185 tgg gec ago gcc att tig ttg ggg ait goa, ctg gtg ait ggc gca ggc Trp Ala Ser Ala Ile Leu Leu Giy Ile Ala Leu Val Ile Gly Ala Gly 627 195 atg git igg Met Val Trp gat tee gte Asp Ser Val 220 ate aac cge tet Ile Asn Arg Ser att Ile 210 gcc agg etc act Ala Axg Leu Thr cgc tat gct Arg Tyr Ala 215 ctc ggt agt Leu Gly Ser act gac aai aag Thr Asp Asn Lys ccc Pro 225 git cci cic ccc Val Pro Leu Pro gati As p 230 agc gag Ser Giu 235 ttg cgt aaa cic Leu Arg Lys Leu cag gcg cig gaa agi atg cgc gig aag Gin Ala Leu Giu Ser Met Arg Val Lys 245 ctg Leu 250 gag Giu gaa ggg aaa aac Giu Gly Lys Asn cta aaa agc cca Leu Lys Ser Pro 270 tat Tyr 255 att gag eag iat Ile Giu Gin Tyr gt Val 260 iat gcg tia act Tyr Ala Leu Thr ctg geg gcg ati Leu Ala Ala Ile ggc gcg gcg gaa Gly Ala Ala Giu ati tia Ile Leu 280 cgc gaa ggi Arg Giu Gly ctg aeg caa Leu Thr Gin 300 ceg ccg gaa gig Pro Pro Giu Val gig Val 290 get cgt iii ace Ala Arg Phe Thr gao aac at Asp Asn Ile 295 ita cia cge Leu Leu Arg 915 963 aai gcg ega aig Asn Ala Arg Met gca cig gig gaa Ala Leu Val Giu acg Thr 310 cag gca Gin Ala 315 aga cig gag aat Arg Leu Giu Asn cgi Arg 320 eag gaa gte gt Gin Giu Val Val ctg Leu 325 act gct git gat Thr Ala Val Asp gig Val 330 geg gca ita iii Ala Ala Leu Phe cgc Arg 335 egc gte age gaa Arg Val Ser Giu geg Al a 340 cgc ace gig cag Arg Thr Val Gin 1011 1059 1107 1155 gca gaa aaa aac Ala Giu Lys Asn ate Ile 350 act tig cat gt Thr Leu His Val cci. act gag gt Pro Thr Giu Val aac gti Asn Val 360 ctg gat Leu Asp get ici gaa Ala Ser Glu ceg Pro 365 gcg tia cig gag Ala Leu Leu Giu cag Gin 370 gcg cig ggg aai Ala Leu Gly Asn aac gee ate gat iii act ccc gag age ggi ige aia aeg eta age gee Asn Ala Ile Asp Phe Thr Pro Giu Scr Giy Cys Ile Thr Leu Ser Ala 1203 gaa gig GiU Val. 395 gat cag gaa tac Asp Gin Giu Tyr acc cii aag gig Thr Leu Lys Val gat ace ggi agt A-sp Thr Gly Ser 1251 1299 ggg Gly 410 ati cct gac tac gcg ctg tca cgt at Ile Pro A-sp Tyr Ala Leu Ser Arg Ile 415 iii Phe 420 gaa egc tti tac Glu~ Arg Phe Tyr ici Ser 425 ttg ceg cgt gca Leu Pro Arg Ala ggg caa aaa age Giy Gin Lys Ser ggi ctg ggg iig Gly Leu Gly Leu geg tt Al1a Phe 440 1347 gtc agt gag Val Ser Giu gig cag gaa. Val Gin Giu 460 gte Vai 445 gee egi tig iii Ala Arg Leu Phe ggc gaa gie Giy Giu Val. acg cig cgc aac Thr Leu Arg Asn 455 cac egi cae ttc His Arg His Phe 470 1395 1443 ggi ggc gig cig Gly Gly Val. Leu gee Al a 465 teg cit cga cii Ser Leu Arg Leu aca tag cttcaaattc tieccacata gtcttcgta Thr 475 <210> <211> 474 <212> PRT <213> Escherichia coli 1478 <400> Met Arg Ile Gly Met Arg Leu Leu Leu Giy Tyr Phe Leu Leu Vai Ala Vai Ala Ala Giy Va]. Arg Phe Val Leu Ala Phe Val. Lys Giu Val Lys Pro Ala Thr Leu Arg Ala Thr Giu Thr Leu Ile Asp Thr Leu Ala Giu Leu Ala Arg Pro Asp Leu Leu Ser Asp Pro Thr His Gi y Gin Leu Ala Gin Ala Phe Asn Gin Leu His Arg Pro Phe Ala Asn Ile Gly Ile Asn Lys Val Arg Asn Giu Tyr His Val Tyr Met Thr Asp Val Gly Gln 115 Ala 100 Gin Gly Lys Val Leu 105 Phe Asp Ser Ala As Lys Ala 110 Thr Leu Arg Asp Tyr Ser Arg Asn Asp Val Trp Gly Gln 130 Tyr Gly Ala Arg Ser 135 Thr Leu Gin Asn Pro 140 Ala Asp Pro Glu Ser 145 Ser Val Met Tyr Val 150 Ala Ala- Pro Ile Met 155 Asp Gly Ser Arg Ile Gly Val Leu Val Giy Lys Pro Asn 170 Ala Ala Met Ala Pro Val 175 Ile Lys Arg Gly lie Ala 195 Ser 180 Glu Arg Arg Ile Leu 185 Trp Ala Ser Aa Ile Leu Leu 190 Ile Asn Arg Leu Val Ile Gly Giy Met Val Trp Ser Ile 210 Ala Arg Leu Thr Arg 215 Tyr Ala Asp Ser Val 220 Thr Asp Asn Lys Pro 225 Val Pro Leu Pro Asp 230 Leu Gly Ser Ser Glu 235 Leu Arg Lys Leu Gin Ala Leu Glu Met Arg Val Lys Leu 250 Glu Gly Lys Asn Tyr lie 255 Glu Gin Tyr Ala Ile Arg 275 Val 260 Tyr Ala Leu Thr His 265 Glu Leu Lys Ser Pro Leu Ala 270 Pro Pro Glu Gly Ala Ala Glu Leu Arg Giu Giy Val Val 290 Ala Arg Phe Thr Asp 295 Asn Ile Leu Thr Gin Asn Ala Arg Met 300 Arg Leu Giu Asn Arg Gin 305 Ala Leu Val Giu Leu Leu Arg Gin Ala 315 Gin Glu Vai Val Leu Thr Ala Vai Asp 325 Val 330 Ala Ala Leu Phe Arg Arg 335 Val Ser Giu His Val Met 355 Arg Thr Val Gin Leu Ala Giu Lys Asn 345 Ile Thr Leu 350 Ala Leu Leu Pro Thr Glu Val Vai Ala Ser Glu Pro 365 Giu Gin 370 Ala Leu Gly Asn Leu 375 Leu Asp Asn Ala Asp Phe Thr Pro Gi u 385 Ser Gly Cys Ile Thr Leu Ser Ala Glu 390 Asp Thr Gly-Ser Gly 410 Val 395 Asp Gin Glu Tyr Thr Leu Lys Val Leu 405 Ile Pro Asp Tyr Ala Leu 415 Ser Arg Ile Lys Ser Ser 435 Glu Arg Phe Tyr Ser 425 Leu Pro Azg Ala Asn Gly Gin 430 Al1a Arg Leu Gly Leu Gly Leu Phe Val Ser Glu Val 445 Phe Asn 450 Gly Glu Val Thr Leu 455 Axg Asn Vai Gln Giy Gly Vai Leu Al a 465 Ser Leu Arg Leu Axrg His Phe Thr <210> 6 <211> 128 <212> DNA <213> Escherichia coli <220> <221> CDS <222> (126) <400> 6 atg aaa ggt cgc ctg Met Lys Gly Arg Leu 1 5 gtt ggc gca gcg ctt Val Gly Ala Ala Leu tta gat gct gtc Leu Asp Ala Val ccg Pro 10 ctc agt tcc cta Leu Ser Ser Leu. acg ggc Thr Gly agt aac aag Sex Asn Lys gcg aaa atc aac Ala Lys Ile Asn ctg cat acc Leu His Thr 96 gta cag gat tta ctc tta cac ctt cct 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 1 Val Gly Ala Val. Gin Asp Axrg Leu Leu Asp Ala Val 5 Pro Leu Ser Ser Leu Thr Gly 10 Leu Ser Asn Lys Leu Ala Lys Ile Asn Leu His Thr Leu Leu Leu His Leu Pro Leu <210> 8 <211> 1174 <212> DNA <213> Escherichia coli <220> <221> CDS <222> (121) (837) <400> 8 agaigcacga tcgagiagge cggataaggc gtttacgccg catccagcat ggaaaacgcg cactttgtta tcaatetggg gccagcaaat gctggcctga tttgttcttg agggaagact 120 atg Met aig cgc aaa atg ctg ctg gcg Met Arg Lys Met Leu Leu Ala aec get cac Thr Ala His gac tac Asp Tyr cag ige Gin Cys gca gca ett Ala Ala Leu 10 agc gtc acg Ser Val Thr gtg aag ggc Val Lys Gly tea gig acg gca atg Ser Val Thr Ala Met ccg cgt gac gat gtg Pro Arg Asp Asp Val gaa aac ggc aat etg Glu Asn Gly Asn Leu att gte age Ile Val Se: ceg caa ace gtg Pro Gin Thr Val eag Gin 40 264 gig ate acg cea gae ggc aac gtg aig tat aac ggt aag caa tat tee Val Ile Thr Pro Asp Gly Asn Val Met Tyr Asn Gly Lys Gin Tyr Ser ctg Leu aat gcc gcc cag Asn Ala Ala Gin gag cag gcg aag Giu Gin Ala Lys tat cag gct gaa Tyr Gin Ala Giu cgt agc acc ctg Arg Ser Thr Leu tgg att gat gga Trp Ile Asp Gly gcg aaa agc cgc Ala Lys Ser Arg gic gag Vai Giu aaa gct cgt Lys Ala Arg agc agc aaa Ser Ser LYS 115 a tt Ile 100 gcg ctg gat aaa Ala Leu Asp Lys att Ile 105 aic gtt cag gag Ile Vai Gin Giu aig ggc gaa Met Gly Giu 110 cag ctg aaa Gin Leu Lys atg cgc agc cgt Met Arg Ser Arg ctg Leu 120 acc aaa ctt gat Thr Lys Leu Asp gcg Al1 a 125 gag cag Giu Gin 130 atg aac cgc ati, Met Asn Arg Ile atc Ile 135 gaa acg cgc agc Giu Th~r Arg Ser ggc ctg acg ttt Gly Leu Thr Phe cac His 145 tat aaa gcc att Tyr Lys Al1a Ile cag gtt cgt gcc Gin Val Arg Ala ggc cag caa ita Gly Gin Gin Leu aai cag gca atg Asn Gin Al1a Met ggc Gi y 165 gga ati ita cag Gly Ile Leu Gin agc att aat gaa Ser Ile Asn Giu atg ggc Met Gly 175 gcg aaa gcg Ala Lys Ala gga agc ctg Giy Ser Leu 195 cig aaa agc ggc Leu Lys Ser Gly ggt Gi y 185 aac cca tia cag Asn Pro Leu Gin aac gig ctg Asn Vai Leu 190 tgg aaa aag Trp Lys Lys ggc ggc cig caa Gly Gly Leu Gin icc Ser 200 tca atc caa acc Ser Ile Gin Thr gag Giu 205 cag gaa Gin Giu 210 aaa gat tic cag Lys Asp Phe Gin cag Gin 215 tii ggc aaa gat Phe G1ly Lys Asp igi agc cgc gt Cys Ser Arg Val gig Val 225 act cig gaa gat Thr Leu Giu Asp agc Ser 230 cgc aaa gec ctg Arg Lys Ala Leu gic Val 235 ggg aai ita aaa Gly Asn Leu Lys iaaiccicia tiiaagacg gcataaiaci iiiiiagcc gtitaaiict tcgttiigtt 897 .00 acctgcctct aactttgtaa gggcgaattc tgcagatatc caicacactg gcggccgctc 957 gagcatgcat ctagagggcc caattcgccc tatagtgagt cgtattacaa ttcactggcc 1017 gtcgttttac aaccgtcgtg actgggaaaa ccctggcgtt acccaactta atcgccttgc 1077 agcacatccc cctttcgcca gctggcgtaa tagcgaaaag gcccgcaccg atcgcccttc 1137 caacagttgc gcacctgatg gccaatggac gcgcctg 1174 <210> 9 <211> 239 <212> PRT <213> Escherichia coli <400> 9 Met Met Arg Lys Met Leu Leu Ala Ala Leu Ser Val Thr Ala Met Thr Ala His Ile Val Ser Val Ile Thr Ala Pro Asp Tyr Gin Cys Ser 25 Val Thr Pro Arg Gin Thr Val Lys Giy Giu Asn Lys Asp Asp Val Gly Asn Leu Gin Tyr Ser Pro Asp Giy Met Tyr Asn Leu Asn Gi y Tyr Ala Ala Gin Arg Arg 70 Trp Gin Ala Lys Asp Al1 a Gin Ala Giu Ser Thr Leu Ile Asp Gly Lys Ser Arg Val Giu Lys Ala Arg Ser Ser Lys 115 Glu Gin Met Leu Asp Lys Ile 105 Thr A.rg Ser Arg Vai Gin Giu Leu Asp Ala 125 Ser Asp Gly Met G.ly Glu 110 Gin Leu Lys Leu Thr Pkie Asn Arg Ile Thr Arg 130 His Tyr 140 Gi y Lys Ala Ile Asp 150 Val Arg Ala Giu 155 Gin Gin Leu .00 Asn Gin Ala Ala Lys Ala Gly Ser Leu 195 Met Gly 165 Val Leu 180 Gly Gly Gly Ile Leu Gin Asp Ser Ile Asn Glu Met Gly 170 1*75 Lys Ser Gly Gly Asn Pro Leu Gin Asn Val Leu 185 190 Leu Gin Ser Ser Ile Gin Thr Glu Trp Lys Lys 200 205 Gin Gin Phe Gly Lys Asp Val Cys Ser Arg Val 215 220 Ser Arg Lys Ala Leu Val Giy Asn Leu Lys 230 235 Gin Glu Lys Asp Phe 210 Val Thr Leu Glu Asp 225 <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> gatgatggtg atggagcgt aaacggcacc aacatgaaa ctttcgcgac agctttttc acacccggaa aacccgaaa agaagataaa cgctatctg Ii a tttacggcat tccggtgtct gatgttgcga cgctggagaa t tgctggcgga acgcggcgtg caggtgttct tcactcaggt 120 c atgctgatat gcaccctggc aacatcttcg taagctatga. 180 t atatcggcat tgattgcggg attgttggct cgctaaacaa 240 g cggaaaactt tatcgccttc tttaatcgcg actatcgcaa 300 17 00 agtggcagag cgaatttgcc gtggacat gccgcaactg ttatccgcaa tcaggtcggt aaaaatgcca gcatagtgtt cgcgttattt agccgacctg tttgtccggt tataatgcgg ctacacgtcg attcgtacgg gtactgttaa gtgttactcc ctegatttat attcctgcgc gaactgcctg ggtaagattg tctcggaatt aatgggggct tggcgcaaaa ctttgtttaa attctggttg tctgtgaacc atctgtttaa agaaaaccct ggaaaacggc tggtgagagc aactggttta cccgcgagct ggcgctacgt gatgcccggc cacgctgatt tcatcatcta ggtgccacca tatctttgag tacggcgcgt gctctacgtc gaagcctttc atttaaagaa cgacagtttg tcagtcaaat tagtatttaa tggttaatgg ttttcaicgc ccacagagga gataccaacg aaaccgctgg cgcttcaata gaaggggiag ctggagtcgt aaagcgccgt cgccagggca catgtacgtc giggcacatt caggtggtct tcaaggcggg acatgt atg Met ttgaagagtt ccgaaatttc tggaagtgca gacgccagct ggattaaaga tctgggtcga agtatttaca agggacaatt cttgttggtc gatcgcctgg ccgtgtaacg ggt ggt Gly Gly 360 420 480 540 600 660 720 780 840 900 960 1015 atc agt Ile Ser itt ggc Phe Gly att tgg cag tta Ile Trp Gin Leu t ig Leu 9gC Gly ati att gcc gtc Ile Ile Ala Val gtt gta ctg ct Val Val Leu Leu acc aaa aag Thr Lys Lys tcc aic ggt Ser Ile Gly tcc Ser gat Asp cii ggt gcg Leu Gly Ala aaa ggc ttt Lys Gly Phe gca atg agc Ala Met Ser gaa cca aag Glu Pro Lys cag gat Gin Asp 1063 1111 1159 1207 1255 1303 aaa acc agc Lys Thr Ser cag gcg gat Gin Ala Asp gct gat tt Ala Asp Phe act Thr gct Ala aaa act atc Lys Thr Ile aat cag gaa Asn Gin Giu cag Gin 75 tct 18 aaa ata gaa Lys Ile Giu gac Asp ggt gcc gat aag Ala Asp Lys gcg aag cgc Ala Lys Arg ttt agc gaa cac-gat aaa gag cag gtg taa gtg ttt gat atc His Asp ctg cia Leu Leu 100 Lys Glu Gin Val Val Phe Asp Ile GJ.y Phe Ser Glu iig gig tic atc aic ggc cic gic git ctg ggg ccg caa cga Leu Vai Phe Ile Ile Gly Leu Val Vai Leu Gly Pro Gin Arg 1351 ctg Leu 115 tca Ser cct gtg gcg gia Pro Val Al1a Vai cig gog aca acg 1.eu Ala Thr Thr 135 aaa Lys 120 acg gia gcg ggc Thr Val Ala Gly igg Trp 125 ait cgc gcg iig Ile Arg Ala Leu 1399 1447 gtg cag aac gaa Val Gin Asn Glu acc cag gag tta aaa oto Thr Gin Giu Leu Lys Leu cag gag ttt Gin Glu Phe aac otg acg Asn Leu Thr 165 ca g Gin 150 gac agt. ctg aaa Asp Ser Leu Lys aag Lys 155 git gaa aag gcg Vai Giu Lys Ala ago ctc act Ser Leu Thr 160 cgc cag get Arg Gin Ala 1495 1543 ccc gaa ctg aaa Pro Glu Leu Lys gcg Ala 170 teg aig gat gaa Ser Met Asp Giu tta Leu 175 gog gag Ala Glu IS0 tog atg aaa cgi Ser Met Lys Arg tee Ser 185 tac gtt goa aac Tyr Val Ala Asn cci gaa aag gcg Pro Giu Lys Ala age Ser 195 gat gaa gcg cac Asp Giu Ala His aic cat aac ccg Ile His Asn Pro gig Vai 205 gig aaa gac aai Val Lys Asp Asn gaa Giu 210 1591 1639 1687 act gog cat gaa Thr Ala His Giu ggC Gi y 215 gia acg cci, gci Val Thr Pro Ala gct Al a 220 goa caa acg cag Ala G~n Thr Gin gec agi. Ala Ser 225 tog cog gaa Ser Pro Giu got gcg gao Ala Ala Asp 245 cag Gin 230 aag cca gaa acc Lys Pro Giu Thr acg Thr 235 cca gag ccg gig Pro Giu Pro Val gia aaa cci Val Lys Pro 240 tcg tog agt Ser Ser Ser 1735 1783 got gaa ccg aaa Ala Giu Pro Lys acc Thr 250 got gca cci tcc Ala Ala Pro Ser ct Pro 255 gat aaa Asp Lys 260 cog iaaac atg tct gia gaa gat act caa cog ctt aic acg cat 1833 Pro Met Ser Val Giu Asp Thr Gin Pro Leu Ile Thr His 265 270 cig att. gag ctg cgt aag cgi ctg cig aac tgo ati ate tog gig ate 1881 Leu Ile 275 Glu Leu Axg Lys Leu Leu Asn Cys Ile Ile Ser Val Ile 285 gig Val 290 ata tic cig igi Ile Phe Leu Cys gtc tat tic gee Val Tyr Phe Ala aat As n 300 gac aic tat cac Asp Ile Tyr His ctg Leu 305 1929 1977 gta icc gcg cca Val Ser Ala Pro ctg Leu 310 ate aag cag tig Ile Lys Gin Leu caa ggt ica acg Gin Giy Ser Thr aig atc Met Ile 320 gec ace gac Ala Thr Asp atg gtg tcg Met Val Ser 340 gig Vai 325 gcc tog ccg te Ala Ser Pro Phe tt Phe 330 acg cog aic aag Thr Pro Ile Lys ctg acc ttt Leu Thr Phe 335 cag gig tgg Gin Val Trp 2025 2073 ctg ait ctg tea Leu Ile Leu Ser ccg gig att ctc Pro Val Ile Leu tat Tyr 350 geg tt Ala Phe 355 atc gcc cca gcg Ile Ala Pro Ala tat aag cat gaa Tyr Lys H13 Giu cgc ctg gig gig Arg Leu Val Val cog Pro 370 cig ctg qit icc Leu Leu Val Ser agc Ser 375 ict ctg cig tt Ser Leu Leu Phe tat Tyr 380 atc ggo aig gcg Ile Gly Met Ala ttc Phe 385 2121 2169 2217 gcc tac ttt gig Ala Tyr Phe Val tit ceg cig gca Phe Pro Leu Ala ttt Phe 395 ggc 'ttc cit gee Giy Phe Leu Ala aat ace Asn Thr 400 geg ccg gaa Ala Pro Giu tic gtt atg Phe Vai Met 420 ggg Gi y 405 gia cag gta tee Val Gin Val 5cr gac ate geg age Asp Ile Ala Ser tat tia age Tyr Leu Ser 415 gaa gig cog GlU Val Pro 2265 2313 geg ctg itt aig Ala Leu Phe Met geg Al a 425 tii ggt gte tee Phe Gly Val Scr gtg gea Vai Ala 435 att gig etg cig Ile Vai Leu Leu tge tgg Cys Trp 440 aig ggg att Met Gly Ile ace Thr 445 teg eca gaa gac Ser Pro Giu Asp 2361 2409 tta Leu 450 ege aaa aaa cge Arg Lys Lys Arg tat gig eig gt Tyr Val Leu Val ggt Gi y 460 gca tie git gte Ala Phe Val Val ggg Gi y 465 atg itg Cig aeg ceg ceg gat gte tic teg caa aeg cig ttg gcg ate 2457 Met Leu Leu Thr Pro Asp Val Phe Ser Gin Thr Leu Leu Al1a Ile 475 480 cct atg tac Pro Met Tyr tgc cys 485 cig itt gaa Leu Phe Glu aic ggt gtc tic tic tca cgc itt tac Ile Gly Val Phe Phe Ser Arg Phe Tyr 490 495 gaa. gag gaa aac gac gct gaa gca gaa Glu Glu Glu Asn Asp Ala Giu Ala Glu 505 510 2505 git ggt Val Gly agc gaa Ser Glu 515 aaa ggg cga aac cgg Lys Gly ALrg Asn Arg 500 aaa act gaa gaa taa Lys Thr Glu Giu 2553 2606 attcaaccgc ccgtcagggc ggttgtcat atg Met gag tac agg Giu Tyr Arg gcg aaa gac Ala Lys Asp 540 aig Met 525 itt gat aic ggc Phe Asp Ile Gly gt Val 530 aat ttg acc agt Asn Leu Thr Ser tcg caa ttt Ser Gin Phe 535 gcg gga gtt Ala Giy Val 2654 2702 cgt gat gat gt Arg Asp Asp Val gta Val 545 gcg cgc gct ttt Ala Arg Ala Phe ga c Asp 550 aat ggg Asn Gly 555 cia ctc atc acc Leu Leu Ile Thr acc aat ctg cgt Thr Asn Leu Arg gaa Giu 565 agc cag cag gcg Ser Gin Gin Ala ca a Gin 570 aag ctg gcg cgt Lys Leu Ala Arg ca g Gin 575 tat tcg tcc tgt Tyr Ser Ser Cys tgg Trp 580 tca acg gcg ggc Ser Thr Ala Gly gta Val 585 2750 2798 2846 cat cci. cac gac His Pro His Asp agc cag igg caa Ser Gin Trp Gin gtg act gaa gaa Val ThLr Giu Glu gcg ati Ala Ile 600 ait gag cig Ile Glu Leu cic gac ttt Leu Asp Phe 620 gcg cag cca gaa Ala Gin Pro Glu gig Val 610 gig gcg ait ggi Val Ala Ile Giy gaa tgt ggt Giu Cys Gly 615 gaa cgc gct Giu Axg Ala 2894 2942 aac cgc aac iii Asn Arg Asn Phe tcg Ser 625 acg ccg gaa gag Thr Pro Giu Giu cag Gin 630 ttt gt Phe Vai 635 gcc cag cia cgc Ala Gin Leu Arg gcc gca gaa. tia Ala Ala Giu Leu atg ccg gia tt Met Pro Val Phe 2990 atg -cac tgi cgc gat gcc cac gag cgg itt atg aca tig ctg gag ccg 33 3038 Met His Cys Arg Asp Ala His Glu Arg Phe Met Thr Leu Leu Glu Pro 650 tgg cig gat aaa Trp Leu Asp Lys 655 cct ggt gcg gtt Pro Gly Ala Val. 660 cat igc ttt acc His Cys Phe Thr c tg Leu 670 ct Leu 675 ggc aca Gly Thr 680 3086 cgc Arg gaa gag atg Giu Giu Met 685 cag gcg tgc gtg Gin Ala Cys Val tgt gga att tat Cys Gly Ile Tyr atc ggc att Ile Gly Ile 695 cgg gaa ttg Arg Giu Leu 3134 acc ggt Thr Gly tig ccg Leu Pro 715 tgg Trp 700 gtt tgc gat gaa Val. Cys Asp Glu cga M~g 705 cgc ggg ctg gag Arg Gly Leu Glu c tg Leu 710 ttg att ccg gcg Leu Ile Pro Ala gag GI u 720 aaa ttg ctg atc Lys Leu Leu Ile gaa Glu 725 act gat gcg ccg Thr Asp Ala Pro 3182 3230 32'78 3326 tat Tyr 730 ctg ctc cct cgc Leu Leu Pro Arg ga t Asp 735 ctc acg cca aag Leu Thr Pro Lys cca Pro 740 tca tcc cgg cgc Ser Ser Arg Arg gag cca gc.c cat Glu Pro Ala His ccc cat att ttg Pro His Ile Leu caa Gin 755 cgt att gcg cac Mgq Ile Ala His tgg cgt Trp Mrg 760 gga gaa gat Gly Glu Asp aca ctg ttt Thr Leu Phe 780 gcC Al a 765 gca tgg ctg gct Ala Trp Leu Ala gcc Ala 770 acc acg gat gcc Thr Thr Asp, Ala aat gtc aaa Asn Val. Lys 775 33*74 ggg att gcg ttt Gly Ile Ala Phe tag agtttgcg 3406 <210> 11 <211> 89 <212> PRT <213> Escherichia coli <400> 11 Met Giy Gly Ile Ser Ile Trp Glh Leu Leu Ile Ile Ala Val Ile Vai Val. Leu Leu Phe Giy Thr Lys Lys Leu Gly Ser Ile Gly Ser Asp Leu 25 Gly Ala Ser Lys Gin Asp Ile Lys Gly Phe Lys 40 Lys Ala Met Ser Asp Asp Glu Pro Lys Thr Ser Asp Ala Asp Phe A-la Lys Thr Ile Ala Asp Lys Gin Ala Asp 70 Thr Asn Gin Glu Gin *7 5 Ala Lys Ile Glu Asp s0 Ala Lys Axg His Asp Lys Glu Gin Val <210> 12 <211> 171 <212> PRT <213> Escherichia ci <400> 12 Val Phe Asp Ile Gly 1 5 Phe Ser Giu Leu Leu Val Phe Ie Ile Gly Leu Val Val Ala Gly Trp Leu Gly Pro Gin Arg Leu 25 Pro Val Ala Val Lys Thr Val Val Gin Asn Ile Arg Ala Leu Ser Leu Ala Thr Thr Giu Leu Thr Gin Giu Leu Lys Leu Gin Glu Phe Asp Ser Leu Lys Lys Ser Val Giu Lys Ala Met Asp Giu Leu Leu Thr Asn Leu Thr 75 Pro Giu Leu Lys Ala Arg Gin Ala Ala Gi u 90 Ser Met Lys Arg 5cr TIyr Val Ala Asn Asn Pro Vai 115 Pro Giu Lys Ala Asp Glu Ala His Thr Ile His 110 Val Thr Pro Val Lys Asp Asn Giu 120 Thr Ala His Giu Gi y 125 A.1a Al a 130 Ala Gin Thr Gin Ser Ser Pro Giu Gin 140 Lys Pro Giu Thr Thr Pro Giu Pro Val Vai Lys Pro Ala, Al1a

145- 150 Asp 155 Al1a Giu Pro Lys Thr 160 Ala Ala Pro Ser Pro Ser Ser Ser Asp Lys Pro 165 170 <210> 13 <211> 258 <212> PRT <213> Escherichia coi <400> 13 Met Ser Val Giu Asp Thr Gin Pro Leu 1 5 Thr His Leu Ile Giu Leu Axg Lys Arg Cys Leu Val Leu Leu Asn Cys Ile Ile 25 Ser Vai Ile Val Ile Phe Leu Ser Ala Pro Tyr Phe Ala Asn Asp 40 Ile Tyr His 1.eu Vai Leu Ile Lys Gin Leu Pro Giy Ser Thr Met Ala Thr Asp Vai Ala Ser Pro Phe Phe Thr Pro Ile Lys Leu Phe Met Val Ser le Leu Ser Ala Pro Val Ile Leu Tyr Gin 90 Vai Trp Ala Phe Ile Ala Pro Ala Leu Ser Ser Ser 115 Lys His Giu Arg Arg 105 Leu Val Val Pro Leu Leu Val 110 Tyr Phe Val Leu Leu Phe Tyr Gly Met Ala Phb Val Phe 130 Pro Leu Ala Phe Gi y 135 Phe Leu Ala Asn Thr 140 Al1a Pro Giu Gly Val 145 Leu Gin Val Ser Thr Phe Met Ala Phe 165 Asp 150 Ile Ala Se: Tyr Leu 155 Se: Phe Val Met Gly Val Ser Phe Giu 170 Vai Pro Val Ala le Val 175 Leu Leu Cys Trp Met 180 Giy Ile Thr Ser 185 Pro Giu Asp Leu Arg Lys Lys 190 Arg Pro Tyr Val Leu Val Giy Ala Phe Val Vai Gly Met Leu Leu Thr 200 Pro Pro Asp 210 Val. Phe Ser Gin Thr 215 Leu Leu Ala Ile 220 Pro Met Tyr Cys Leu Phe Giu Ile Gly Val 225 230 Phe Phe Sex Arg Tyr Val Gly Lys Gi y 240 Arg Asn Arg Giu Glu 245 Giu Asn.Asp Ala Gi u 250 Ala Giu Ser Giu Lys Thr 255 GiU GiU <210> 14 <211> 264 <212> PRT <213> Escherichia cli <400> 14 Met Glu Tyr Arg Met Phe Asp Ile Gly Val Asn Leu Thr Ser Ser Gin Phe Ala Lys Val Asn Gly Asp ArgjAsp Asp Vai Ala Arg Ala Phe Asp Ala Gly Ser GIn Gin Leu Leu Ile Thr Thr Asn Leu Arg Giu Ala Gin Lys Leu Al1a Arg Gin 55 Tyr Ser Ser Cys Trp Ser Thr Ala Giy Val His Pro His Asp Ile Ile Giu Leu Ala Ser Gin Trp Gin Ala V&I Thr Glu Val Ala Ile Gly Giu Ala Gin Pro Giu Giu Cys Gly Leu Asp Ala Phe Val 115 Asn Arg Asn Phe Ser 105 Thr Pro GiU Giu Gin Giu Arg 110 Met Pro Val Ala Gin Leu Arg Ala Ala Glu Leu Asn 125 Phe Met 130 His Cys Arg Asp Ala 135 His Giu Arg Phe Met 140 Thr Leu Leu Giu Pro.Trp Leu Asp Lys Leu Pro Gly Ala Val Leu His Cys Phe Thr Gly .00 145 Thr Arg Giu Glu 150 Met Gin 165 Val Cys 155 Cys Ala Cys Val Gly Ile Tyr 160 Ile Gly 175 Arg Glu Ile Thr Gly Trp Leu Leu Pro Leu Asp Glu A.rg 185 Lys Gly Leu Giu Le u Ile Pro Al1a Leu Leu Ile 195 Pro Tvr Leu Giu 205 S er 190 Thr Asp Ala Ser .Arg Arg Leu Pro Arg 210 Asn Giu Asp 215 Pro Thr Pro Lys Pro 220 Arg Pro Ala His Hi~s Ile Leu Ile Ala His 225 Axrg Gly Glu Asp Ala 245 Gi y Trp Leu Ala Al a 250 Thr Asp Ala As n 255 Lys Thr Leu Phe 260 Ile Ala Phe <210> <211> 586 <212> DNA <213> Escherichia coli <220> <221> CDs <222> (170) (370) <400> tcttaaacaa ccgtcgcttt, gcgccgccgc aattattatg tgattcacci tgttacagat tgctattgtg tgcgcgcgtc tggttttiaa ggcgcgttct gttgccggtt atatgtcaag atgttttttt actcggcgct gaatgaccgt taaiattctc 120 aaggtatct at~g ggt gag 178 Met Gly Giu 1 ctg gtc gtt cig ctg 226 Leu Val Val Leu Leu gac ctt gga gcg gcc 274 att agt ati acc aaa ctg ctg gta gtt gcg gcg Ile Ser Ile Thr Lys Leu Leu Val Vai Ala Ala 10 tt.ggg act aag aag tta cgt acg ctg ggc gga 26 ?he Gly Thr Lys Lys Leu Arg Thr Leu Gly Gly 25 30 att aaa ggg tic aag aag gcg aig aat gat gac Ile Lys Gly Phe Lys Lys Ala Met Asn Asp Asp 45 aaa ggc gca gac gtt gat ctt cag gct gaa aag Lys Gly Ala Asp Val Asp Leu Gin Ala Glu Lys 60 tgacgtggcg agcaggacgc tccctcaata tcttgttcga agcgggtttt ttatcagaca gatgtaagta aitattacag tttcgcctgc aaatcggcgt ggtaagaaga gcggacaaac aaagcccatc gccagcgctt cgctttcatt tcgtcg <210> 16 <211> 67 <212> PRT <213> Escherichia coli <400> 16 Met Gly Glu Ile Ser Ile Thr Lys Leu Leu Val 1 5 10 Val Leu Leu Phe Gly Thr Lys Lys Leu Arg Thr Asp Leu Gly Ala Ala gat gct gcg gcg aaa 322 Asp Ala Ala Ala Lys ctc tct cat aaa gag 370 Leu Ser His Lys Glu tacaaaaacc cgcttcaaaa 430 gattacttaa cttccatccc 490 ggaccgcatg cagcatgggt 550 586 Val Ala Ala Leu Val Leu Gly Gly Asp Leu Asn Asp Asp Asp Ala Ala Glu Lys Leu Ser Gly Ala Ala Ala Ala Lys His Lys Glu 25 Ile Lys Gly Phe Lys Lys Ala Met 40 Lys Gly Ala Asp Val Asp Leu Gin <210> 17 <211> 4200 <212> DNA <213> Salmonella typhimuriun <220> <221> CDS <222> (1444) <220> <221> CDS <222> (1450).. (1722) <400> 17 cgcaagtc-aa tgtCgtcccg ctaacaaaga ggcagcgtga atcacagagg aacatgtatg tcgtcgtact gctgttcggc ctatcaaagg ctttaaaaag aggacgctga tttiaccgct acgctaaaag ccaagataaa tgctgttagt gttcgttatc taaaaacggt agcgggctgg aactgactca ggaactgaaa cgagcctgga aaatctgact cggagtcgat gaaacgcacc ataccatcca taatccggtg ccgccgctga aacacaggcg tgcctgagtc gacggaaacc cgcctgttgt cgaatcttc gtcgtatgta aggataatgt ggtggtatca accaaaaaac gccatgagcg aaatctatcg gagcaggiat ggcctcattg attcgcgcgt cttcaggagt cccgaactga tacagcgcta gtaaaaggga agcgcgccgg gcttccgtag ccctcgtcga aaagtatgtg giataatgcg gtatttggca tcggttccat atgatgatgc cggataagca aatccgtgtt tgttggggcc tgcggtccct tceaggacag aagcatctat acgaicccga acgaaacgca aacaaaagcc ccacgataga gtgataaacc aatagggcgg gccctaataa gttgttgatt cggttccgat caaacaggat aggcgaagcg igatatcggt gcaacgattg tgcgacaacg tctgaaaaaa ggatgaactg acaagcgagc gcatgagggc gga gcccgtt cgccgagaag gtaaac atg Met gcgaaagcgg ticaicatot gttgccgtta cttggcgcgt aaaaccagtc aaaaaggaag tttagcgaac ccagtagcgg gttcagaatg gtcgaaaagg cgtcaggcgg gatgaagcgc gtcacccctg aaagctaacg aaatccgctg gct gta Ala Val 120 180 240 300 360 420 480 540 600 660 720 780 840 900 955 gaa gat act caa ccg ctt atc acg cat cig atc Glu Asp Thr Gln Pro Leu Ile Thr His Leu Ile 10 ctg-cta aac tgc atc gtc gca gta ctt ctg att 28 gag ttg cgt aag cgc Glu Leu Arg LYS AXg ttt ctg gcg tta att 1003 1051 Leu Leu Asn Cys Ile Ala Val Leu Leu Ile 30 Phe Leu A-la Leu Ile tat tic gcc aat Tyr Phe Ala Asn att tat cat tta gtc gcc gca ccg cig Ile Tyr His Leu Val Ala Al1a Pro Leu ati aaa Ile Lys 1099 cag aig ccg Gin Met Pro iii tit acg Phe Phe Thr ggg gcg aca atg Gly Ala Thr Met a ii Ile gcg acg gat gig Ala Thr Asp Val gog tcg ccg Ala Ser Pro atc ita. tcc Ile Leu Ser cci atc aaa cic Pro Ile Lys Leu tic atg gig tct Phe Met Val Ser ttg Leu gcg cci Ala Pro tat aag Tyr Lys 100 gic ait tig tac Val Ile Leu Tyr cag Gin git igg gcc tt Vai Trp Ala Phe gcc ccg gog cig Ala Pro Ala Leu 1147 1195 1243 1291 1339 cat gag cgi His Giu Arg cgt cig gic gia cot Arg Leu Val Val Pro 105 ggt atg gcc tic gcc Gly Met Ala Phe Ala 125 ctg gia. icc ago Leu Val Ser Ser tog Ser 115 cig cii tic tat Leu Leu Phe Tyr tat iii gic gia, Tyr Phe Val Val tic cci Phe Pro 130 tig goc tt Leu Ala Phe tog aca gat Ser Thr Asp 150 ggt Gi y 135 tic cig acg cat Phe Leu Thr His a cg Thr 140 gog ccg gaa ggg Ala Pro Giu Giy gia cag gt Val Gin Val 145 cii tii atg Leu Phe Met 1387 ato gcc ago tat cii ago tit gic atg Ile Ala Ser Tyr Leu Ser Phe Val Met 155 1435 gcc tt Ala Phe 165 atg ggc Met Gly 180 gcg tagcc iii gaa gig ceg gig gog ait gig tig crtg tgc igg 1485 Al1a Phe Giu Val Pro Vai Ala Ile Val Leu Leu cys Trp 170 175 aic aco acg cca Ile Thr Thr Pro gat tig cgi aaa Asp Leu Arg Lys aaa, Lys 190 cgg cci tat ato Arg Pro Tyr Ile 1533 1581 otg Leu 195 gic ggg gca tic Val Gly Ala Phe at Ile 200 gig gga atg cig Val Gly Met Leu acg cog oca gat Tkxr Pro Pro Asp gt Val 210 tic. tcg caa acg tig otg gcg ata cog aig tac igo cig iii gaa att 12 1629 Phe Ser Gin Thr Leu Leu Ala Ile Pro Met Tyr 215 220 ggc gtt tic tgc tca cgc ttt tat gtc ggt aag Gay Val Phe Cys Ser Axrg Phe Tyr Val Gly Lys 230 235 gaa gat aac gag gcc gaa acc gaa aag gcc gag Glu Asp Asn Glu Ala Glu Thr Glu Lys Ala Glu Cys Leu Phe Glu Ile 225 cga cgg acg cgc Arg Arg Th~r Arg 240 cac act gaa gac His Thr Glu Asp gac 1677 Asp 1722 taaacacaac ttaatttaac cggcgggagt taaaactggc gcagtcagtg icgtcgctat cgcccgccag cagtagccag aaaaggtatg gcggcgctac gtcacccgcg cggtgagigc aggagcgtgc ctttcaggcg tgcactgccg ttcctggtgC atagagggct tacgtgaact atctgttgcc tgcctcacat cgatgacaga cttgcgaaaa taacatcgaa gccttccgtg gggcttgtag aagcgcacaa ggacgcgcat aatactgcac ctatatcggt cttaccgttt tcgcgatctt cctggagcgc tgccaacgcc ccggtgtttt cgcgtttcgc atgatgacgc atagaaagct aatggctgac ggcggttgtC tttgcaaaag ctactgaceg ccccattqtt tctgaagacg gggctggatt cagctacaaa gagcgatttc tgctttaccg attaccgggt attccagcgg acgccgaaac atagcgctat agaaccttat ttacgctctg catccggttc tatcgccggg gatgaaiaac gccgcgcgtg atatgggggc atcgtgatga gaacgaacat ggicgacggc ccattattgc tcaatcgcaa ttgccgccga tggtattgct gttcacgcca. gggtttgcga aaaagctact caacgtcacg ggcgtggtga ttgaggttgt. cttcacttct ggtaaaaatc atagggggtt gctggaaggc gcgttgattg aagcatgttt tgiggtcgcc ccatgaaagt tggcgtccat gctggcgaac tttttccacg attgcagata tgatccctgg gcaaatgcag cgaacgacgc gatagaaacc acgcaacgag agatccgcaa attctgaacg ttattgagta. gctttcagcc tcaggatcga acgatcgcag tagtggtatg gatattggcg 1782 cgtgcgtttg 1842 cagcaggcgt 1902 ccccatgaca 1962 cagccggaag 2022 ccgcaggagc 2082 ccaatcttta 2142 ctggatagtc 2202 gcctgtgtgg 2262 gggcttgagc 2322 gacgcgccgt 2382 cccgcgtatc 2442 tggttagcgg 2502 atcgctaaat 2562 aattaagcag 2622 cttcaaatgc 2682 caacgccttc 2742 gatgccgcca. 2802 tatcacttcc 2862 .00 ggatcaaat ccgcgtacca aggtgttcct ataatgactc attatacact -aatttaacaa ggctacaatg gcagggggaa cgctgaccgc cgccatgccg gcaggatgat tgagccgccg gaatatgccg tgatgtcgat gattacctgg ttatcgtcag cggcgcgctg cgtcgcattg ctgtcggagt ttctacgatc cggagacgta acagcgtaga ctcgtctatc caacgaacag ttttttccag gagcacgctg ttatccgctt tcatccttta aaatacagca gacgccatga ctaaaacgca acgctgcgtg gtgctgtgca gtttccgcct aaagcgtttc acgaaacggt ttaacgcgtc ggactgacgg cagttgatag gattttcagg ggcgccgatc atgcctttgc tggagtgctg tgcgatcata tgcatctata tcaaagtc ataatiagga ggtgatcatc aagttgcccg gttcggggCg agccgtatct tcccgatgat aatatcacga tcacgctacc ccggtggac acctttttgg taegggaagt gcgatctgtt tacgcggcgc ttcctgtcat taacgcgtgg gtaaaaataa a gtggttagc cggcacgata gggcctgctg cagcgcgaga cggcatatat tcactatacg aagagcggtt ggtgtcaggc cgtttgcagt caagcatagc ggattagcgt gaacgccgta tttacgcgac tgtggatcct ggcgttgctg cacgccaaaa gggtaaatta tgacaagctg gccttgccag gacctgttgg tccgcacaaa gctgattatg cgcgcgtccg cttggcgccg cgcggcacga tatcttgaag gagtgatagc cgcgcatgag cgctgacgga aacttaccgc acagtaaata aaaagccatg tggttgccag taatgatgcg ttcctgacgc catctggaaa tttgaaaatc cgcgtggcga ttagcgtttc ccgcagttta cagaaaatcg ccggacgacg gagcggcaaa cgctggctgt ggtgaacgtt tgacicctgt aaactgaagt tacatgagcg tcgtcttacg ctcgtatagg ggtacgtttt ttgtctttcg ccaggattgc cgcgaagtta agttcacgct cttaccaaga tacttgagca tcacggaaat ctaaaggtta tgggcatggg ttaaagaacc agcaagtgct cgtctggcga ccgcgccgct acctgggcat ctcaccgcgg tcccggtctc tccegatact ggttaatgct gagagatgcg icacgcaata tgcctcatat 2922 2982 3042 3102 3162 3222 3282 3342 3402 3462 3522 3582 3642 3702 3762 3822 3882 3942 4002 4062 4122 4182 4200 <210> 18 <211> 166 <212> PRT <213> Salmonella typhixnurium <400> 18 Met Ala Val Glu Asp 1 5 Thr Gin Pro Leu Thr His Leu Ile Glu Leu A.rg Lys Arg Leu Asn Cys Ile Ala Val Leu Leu Ile Phe Leu Ala Ala Pro Ala Leu Ile Tyr Phe A-la Asn Asp Ile Tyr His Leu Leu Ile s0 Lys Gin Met Pro Gin Gly Al1a Thr Met Ala Thr Asp Val Al a Ser Pro Phe Phe Pro Ile Lys Leu Thr Phe Met Val Val Trp Ala Phe Ser Ie Leu Ser Ala Val Ile Leu Tyr Ile Ala Pro Ala Leu Ser Ser Ser 115 Lys His Giu Arg Arg 105 Leu Val Val Pro Leu Leu Val 110 Tyr Phe Val Leu Leu Phe Tyr Ile 120 Gly Met Ala Phe Ala 125 Val Phe 130 Pro Leu Ala Phe Gi y 135 Phe Leu Thr His Thr 140 Ala Pro Giu Gly Gin Val Ser Thr Ile Ala Ser Tyr 5cr Phe Val Met Ieu Phe Met Ala Phe Ala 165 <210> 1.9 <211> 91 <212> PRT <213> Salmonella typhimuriuu <400> 19 Phe Glu Val Pro Val Ala Ile Val Leu Leu Cys Trp Met Gly Ile Thr Thr Pro Glu Phe Ile Val Leu Leu Ala Asp Gi y Leu Arg Lys Lys Met Leu Leu Ile Pro Met Ser Arg Tyr 55 Lys Thr 40 Cys Arg Arg Pro Tyr Ile Leu Val Gly Ala 25 Pro Pro Asp Val Phe Ser Gin Thr Leu Phe Glu Ile Gly Val Phe Cys Arg Thr Arg Asp Glu Asp Asn Glu 75 so Phe Tyr Val A.1 a Glu Thr Glu Lys Glu His Thr Glu Asp <210> <211> 2601 <212> DNA <213> Neisseria Ineni <220> <221> CDS <222> (1572).. (2339) <400> agacaaaatc ctaaaaaaa caaaaacccg tcccacctg tctgacacac cacgacctg tttgtcgggc ttggccgaa cacttecca cattcaatc aacigtattt tctgcaaaa ggcgaaatgg tgtca cccaaagtcc atttcgatti aaaatgatgc tgaaagttci accctgatca acaccggaa. ngitidis g a a c t a c tgattgaaga tttacgaagt aggcggaaga aagccgctcg gtctgaccgc cgccgccaaa agacatcaac gttggcacac cgaaatcgcc a ggcggcgga ggcgggcgaa tgccgactta cgtattggac cacagaatct tgttcagacg gacattccgg cccgctgctc gccgcgcccg aaagcggcag caagaggtct gtgtigatgg tggttcaca gjaa cttgcgc tgaatttata gcatcggagc cgcaaaccgt cggttcatct aacatcagcc gactggcaga tceacctgca caiccaaaga ccatgattct gccgccaagg ttaaaatccg cgttatggac ctaigaagac g.ctgc igatt ccttttggga cggcttcaaa tatacacatc .00 atgggcacac ca teatgggc attcggcacc caaacagggg acacaaaaaa ttttgtcggC caccgccgga tgacacgcaa tgctcaggtt catticcgac cggtgtcgat ttccgacgtt gcaaaccggc cctgactgct cgctgttgaa ccgtataaac agtttttctc aaaaaactgc ctgaacgaag gacgaagaca attatcgccc cggctcatcg atcgaactgg cgagacagcc ggtctgaagc gaaaacggca atgccgtccg agtacagccg tctgccgccg acecctgttc Cgttatttca tgacgcactg gcaacgtcgg gtacagacgg aagegtaatt tgattgteci gcaggctgca aagaactaag tcaaagaaac cttgggaaaa atccctttce aacgttccta aacccgcgga cacccgtcgt cgcataccac caatcaaccc gattatcgta caaagacctc caaagaagcc tatgtttgat cggccccgaa acgctttgtc gaaggcaaag cggtacggat actgcccgaa cgatgcggea cgcitccgcc aaccgaccaa acagaccgtc ttcgcigcgt ctaatactta ctgattatcg ggcggtgcgg caaaaagacg ttcggtttgg cCtgecCg ggcagcgtca caggaatttg atggagggta cagcgcacgc aacaccctat gaaacccttg gaccgtgcat gaagtcagct aaacaggcaa cttaaggata tcgttttgat ttcatgactt atgtaatcga gcgagctggt aggccgcccg aacaggaatt aagctgccge atctgcacga ctgctgattt tagacggcat gggacagcgg ggcgggaaia atatcgaiac taagccgcaa 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 acgcgatttg cgtcctaaat cccgcgccaa acctaaattg cgcgtccgta aatcataaag 1560 agggcaatc g gtg tcc gaa aca caa aac gaa caa tec gte caa cog ctt 1610 Val Ser Glu Thr Gin Asn Giu Gin Pro Val Gin Pro Leu gtc gag cat ctc atc gag cig cgc cgc cgc ctg atg tgg acg gtt gtc Val Glu His Leu* Ile Glu Leu Arg Arg Arg Leu Met Trp, Thr Val Val 20 ggt atc tta gtc tgc tit ttc ggc cia atg ccg itt gcc caa caa ctC Gay Ile Leu Val Cys Phe Phe Gly Leu Met Pro Phe Ala Gin Gin Leu 35 -40 tat act ttt ate gcc gac ccg ctg atg gca aac ctg ccc aaa gac ac Tyr Thr Phe Ile Ala Asp Pro Leu Met Ala Asn Leu Pro Lys Asp Thr 55 1658 1706 1754 agc atg ati gcc ace gat gte atc Ser Met Ile Ala Thr Asp Val Ile gca Al a 70 cea ttt ttc gig Pro Phe Phe Val ceg gic aaa Pro Val Lys aeg etc tac Thr Leu Tyr 1802 git acc ctg Val Thr Leu so atg gcg gca ttt Met Ala Ala Phe ita Leu ati tcg cig ceg Ile Ser Leu Pro 1850 caa ate Gin Ile tgg gca tie gte Trp, Ala Phe Val gee Al a 100 ccc gea etc tae Pro Ala Leu Tyr aac gaa aaa ege Asn Giu Lys Arg 1898 cig Leu 110 ati aeg ceg etc Ile Thr Pro Leu etc tee -age gtc age cig ttt tie atc Leu Ser Ser Val Ser Leu Phe Phe Ile 120 1946 aig gca itt gcc met Ala Phe Ala tac Tyr 130 itt tig git ttc Phe Leu Val Phe gte att tic aaa Val Ile Phe Lys tic ct Phe Leu 140 1994 gcc agc gt Ala Ser Val tac etc tee Tyr Leu Ser 160 cct gtc ggi gtc Pro Val Gly Val aat Asn 150 aig gcg aca gac Met Ala Thr Asp ate gac aaa Ile Asp Lys 155 aca aeg tt Thr Thr Phe 2042 2090 tic ate ttg ggg Phe Ile Leu Gly a ig Met 165 itt gte gea tic Phe Val Ala Phe ggt Gi y 170 gaa gtc Giu Val 175 ccc att gtc gt Pro Ile Val Val ate Ile 180 ctg ita ace aaa Leu Leu Thr Lys ggt gig gia aca Gly Val Val Thr gte gge geg tt Val Giy Ala Phe 205 ace Thr 190 gaa cag cte aaa. Giu Gin Leu Lys ege ALrg 195 gee cge ccc tat Ala Arg Pro Tyr 2138 2186 2234 2282 gte ait gee gce Val Ile Ala Ala ate aeg eeg ccc Ile Thr Pro Pro gat Asp 215 gig ait tea caa Vai Ile Ser Gin ace cig Thr Leu 220 tic gga Phe Gly cii gee ati Leu Ala Ile ege iii tic Arg Phe Phe 240 cig att ete tta Leu Ile Leu Leu tac Tyr 230 gaa gca ggt at Giu Ala Gly Ile acg eea egi tea Thr Pro Arg Ser gaa Giu 245 eag gat ggc gac Gin Asp Giy Asp ata. Ile 250 cag eeg cci Gin Pro Pro 2330 gca aca acc tgacactatg ccgtccgaac ctccgccica taccgccaca 2 37 9 Ala Thr Thr 255 gattaaggaa tacctttgaa taccctctat ttaggttcaa acagcccgcg ccgaatggaa 2439 atcctgacac agttgggcta tcaggtcgtc aagctgcctg ccaacatcga cgaaacggtc 2499 agacagaacg aagaccctgc ccgttacgtt caaaggatgg cagaagaaaa aaaccgaacc 2559 gccctgaccc tcttttgcga aaccaacggc acaatgcccg at 2601 <210> 21 <211> 256 <212> PRT <213> Neisseria reningitidis <400> 21 Vai Ser I Giu Thr Gin 5 Asn Giu Gin Pro Val 10 Trp Gin Pro Leu Val Giu His Leu Ile Glu Leu Arg Arg Arg Leu Thr Val Val Val Cys Phe Ile Al1a Asp Phe Gly Leu Met Ala Gin Gin Leu Thr Gly Ile Leu Tyr Thr Phe Ser Met Ile Pro Leu Met Thr Ala 55 Pro Leu Pro Lys Asp Val Ala Met Asp Val Ile Phe Phe Val Lys Val Thr Leu Ala Ala Phe Leu Pro Ser Leu Pro His 90 Asn Leu Tyr Gin Ile Trp Ala Phe Vai Pro Leu Vai 115 Ala Tyr Phe 130 Ala Leu Tyr Giu Lys Arg Ser Ser Val Ser 120 Val Phe Phe Ile Gi y 125 Leu Leu Ile Thr 110 Met Ala Phe Ala Ser Vai Leu Val Phe Ile Phe Lys Phe 140 Thr Pro Vai Gly 145 Vai Asn 150 Met Ala Thr Asp Ile Asp Lys Tyr Leu Ser Phe Ile Leu Gly Met 165 Phe Val Ala Phe Gi y 170 Thr Thr Phe Giu Val Pro 175 Ile Val Val Leu Lys Axg 195 Ile 160 Leu Leu Thr Lys Gly Val Val Thr Thr Giu Gin 190 Val Ile Ala Ala Arg Pro Tyr Val 200 Ile Val Gly Ala Ala Ile 210 Ile Thr Pro Pro Asp 215 Val Ile Ser Gin Leu Leu Ala Ile Leu Ile Leu Leu Tyr 230 Giu Ala Giy Ile Trp, 235 Phe Gly Arg Phe Phe 240 Thr Pro Arg Ser Gi u 245 Gin Asp Gly Asp .le 250 Gin Pro Pro Al1a Thr Thr 255 <210> <211> <212> <213> <220> <221> <222> <220> <221> <222> <220> <221> <222> <220> <221> <222> <400> ggcta 22 4604 DNA Escherickxia coli CDS (2982) (4082) CDS (1534).. (2637) CDS (749) (1531) CDS (746) 22 gtt gat gat aat ttg aaa ggt caa ggt gca gga aaa aat ttt tta Val Asp Asp Asn Leu Lys Gly Gin Giy Ala Giy Lys Asn Phe Leu tcg ctg ata aag tac agc gag aca gat tat aca att tat tgt gac caa 98 Ser Leu Ile Lys gat gat att igg Asp Asp Ile Trp aat gaa ati aaa Asn Giu Iie-Lys Tyr Ser Giu Thr Asp Tyr Thr Ile Tyr Cys 25 Asp Gin tia gaa aac aaa Leu Giu Asn Lys itt gaa ita gta Phe Giu Leu Val aag tat gca Lys Tyr Ala gtt tat gct Vai Tyr Ala 146 194 tig aat gta. Leu Asn Val tca. Ser gat gcg cct icg Asp Ala Pro Ser gat ggc Asp Giy tat gct tat aig Tyr Ala Tyr Met gat Asp ggt gag ggt aca Gly Giu Gly Th: gat iii tct ggg Asp Phe Ser Gly a ta Ile ici aac aat cat Ser Asn Asn His gai caa tia aag Asp Gin Leu Lys ga t Asp itt ctt itt ttt Phe Leu Phe Phe ggt gga. tac caa Gly Gly Tyr Gin gga, Gly 100 tgt tct ait aig Cys Ser Ile Met aat cgt gca. aig Asn Arg Ala Met acc aaa Thr Lys 110 itt cit cig Phe Leu Leu aca ita gct Thr Leu Ala 130 tat cga gga. ttt Tyr Arg Gly Phe tat cia cat gac Tyr Leu His Asp gat atc aca Asp Ile Thr 125 ccg aaa tac Pro Lys Tyr gca tac gct cii Ala Tyr Ala Leu ggt Gi y 135 aaa git tat ttt Lys Val Tyr Phe cit atg Leu Met 145 ita tat aga cag Leu Tyr Arg Gin C8 C His 150 acg aat gcg gia Thr Asn Ala Val act Thr 155 ggt aic aaa aca Gly Ile Lys Thr cgc aat gga ttg A.rg Asn Gly Leu tct aaa tit aaa Ser Lys Phe Lys cca gia aac tat Pro Vai Asn Tyr tta tca cga aaa. Leu Ser Arg Lys cat His 180 tat cag gia aaa Tyr Gin Val Lys aaa, Lys 185 tct ttt ttt gaa, Ser Phe Phe Giu igi aac Cys Asn 190 agc tct atc Ser Ser Ile tta Leu 195 ica gag acg aat Se: Glu Thr Asn aaa Lys 200 aaa gtt itt tig Lys Val Phe Leu gat tit ati Asp Phe Ile 205 ica ttt tgt gaa, tca aat aat aaa, itt aca, gat tii iii aag tta. tgg Ser Phe Cys 210 Giu Sex Asn Asn Lys Phe Thr Asp Phe Phe Lys Leu Trp 215 220 aac agt aga act aaa tta ita tta aaa Asn Ser Arg Thr Lys Leu Leu Leu Lys 235 cga ggt AMg Gly 225 ggg itt aga tta Gly Phe Mrg Leu aat As n 230 tia ata cgg aga Leu Ile Arg Arg tti aat cgg caa Phe Asn Axg Gin aaa Lys 245 cat His 260 tit agc ga atg att tca ata ctt aca cct Phe Ser Met Ile Ser Ile Leu Thr Pro 250 act Thr 255 act ita tca agg Thr Leu Ser AMg cia Leu 265 tic aat tct. ct Phe Asn 3cr Leu tta caa act gat Leu Gin Thr A-sp aaa Lys 275 gat tit gag tgg Asp Phe Glu Trp a ta Ile 280 ata att gat gat Ile Ile Asp Asp ggt agt Gly Ser 285 ata gat gca Ile Asp Ala ttt gac ttg Phe Asp Leu 305 gcg gta cit gta Ala Val Leu Val gat itt aga aaa Asp Phe Arg Lys aaa tgt gat Lys Cys Asp 300 ccc atg gct Pro Met Ala 913 961 att tat tgc tat Ile Tyr Cys Tyr cag Gin 310 gaa aat aat ggt Giu Asn Asn Giy tia aac Leu Asn 320 gct ggt git aaa Ala Giy Val Lys gat Al a 325 tgt aga ggc gat Cys MLg Gly Asp tat Tyr 330 atc itt ait gt Ile Phe Ile Val ga c Asp 335 agt gat gat gca Ser Asp Asp Al1a act ccc gat gcc Thr Pro Asp Ala aaa tta att. aaa L~is Leu Ile Lys gaa Glu 350 1009 1057 1105 tca ata cat gat Ser Ile His Asp tgc cys 355 tta tct gag aag Leu Ser Glu Lys gaa Glu 360 agt ttc agc gga Ser Phe Ser Gly gtc ggt Val Gly 365 ttt aga aaa Phe Arg Lys aat tct tca. Asn Ser Scr 385 gca Ala 370 tat ata aaa ggg Tyr Ile Lys Gly 999 Gly 375 ati att ggt aat Ile Ile Gly Asn gat tia aat Asp.Leu Asn 380 att agc aat Ile Ser Asn 1153 1201 gaa cat ata tac Giu His Ile Tyr tia aat gcg act Leu Asn Ala Thr tta ata aat ggt gat gtt gca tat tgt ttt aaa aaa gaa agt tig gta 14 1249 Leu Ile 400 Asn Gly Asp Val Tyr Cys Phe Lys Lys 410 Glu Sex Leu Val aaa aat cca tic ccc Lys Asn Pro Phe Pro 415 ata gaa gat gaa Ile Glu Asp Glu aaa Lys 425 itt gtt cca gaa Phe Val Pro Glu tat att tgg aat Tyr Ile Trp Asn aaa Lys 435 ata act gac aag Ile Thr Asp Lys gcg Al a 440 aag att cga ttt Lys Ile Arg Phe aac ata Asn Ile 445 12917 1345 1393 agc aaa gt Ser Lys Val aat tic cat Asn Phe His 465 tat cit tgt Tyr Leu Cys gag tat Glu -Tyr 455 cit gat gat ggt Leu Asp Asp Gly cit ict aaa Leu Ser Lys 460 aag ati tat Lys Ile Tyr aac cag ctt aaa Asn Gin Leu Lys aaa Lys 470 tac cca aag ggg Tyr Pro Lys Gly 1441 iac aaa Tyr Lys 480 gat caa aga aaa Asp Gin Arg Lys gag aaa act tat Giu Lys Thr Tyr aaa aaa aca aag Lys Lys Thr Lys aig Met 495 aaa Lys 510 cag Gin cia ait aga tat Leu Ile Arg Tyr ata cia itt gic Ile Leu Phe Val git tgt cti tia Val Cys Leu Leu 530 caa tgi igi tat Gin Cys Cys Tyr aca ggt tta ggc Thr Gly Leu Gly gag aaa ata aa atg Giu Lys Ile Met gga ggt gct gag aag Gly Giy Ala Glu Lys 525 1489 1536 1584 1632 gct gat aaa tia Ala Asp Lys Leu tia agc: ggg cac Leu S'er Gly His cat gia His Val 540 aag ait at Lys Ile Ile gaa aat aat Giu Asn Asn 560 cit gga cat atg Leu Gly His Met tct Ser 550 aat aai aaa gic Asn Asn Lys Val itt cct agc: Phe Pro Ser 555 aac att ict Asn Ile Ser 16800 1728 git aat giC att Val Asn Val Ile aa t Asn 565 gia aai aig tca Val Asn Met Ser gga gt Gly Val 575 ata aaa ggi igi Ile Lys Gly Cys aga ait aga gat Arg Ile Arg Asp gt Val. 585 ata get aat tic Ile Ala Asn Phe 1776 aaa cca gac ati gia cac: agi cat aig itt cat gca. aac ati ate: act 12 1824 Pro Asp Ile Val His 595 Ser His Met Phe His 600 Ala Asn Ile Ile aga ttg tot gta Arg Leu Ser Vai gga ate aaa aac Gly Ile Lys Asn cct ggt ati ata Pro Gly Ile Ile tca act Ser Thr 620 tat aga Tyr Arg 1872 1920 gca cat aat Ala His Asn ata ace gat Ile Thr Asp 640 aaa Lys 625 aat gaa ggt ggg Asn Giu Gly Gly tat Tyr 630 ttc: aga atg cic Phe Arg Met Leu tgt tta agt gat Cys; Leu Ser Asp t gt Cys 645 tgt aca aat gtt Cys Thr Asn Val agc Ser 650 aaa gaa gca Lys Giu Ala 1968 gtg gat Val Asp 655 gag ttt tta cgg Giu Phe Leu Arg aaa gco ttt aat Lys Al1a Phe Asn cco Pro 665 gct aaa gca att Ala Lys Ala Ile act Tb r 670 atg tat aat ggg Met Tyr Asn Gly ata Ile 675 gat ace aat aaa Asp Thr Asn Lys aaa ttt gat tta Lys Phe Asp Leu 2016 2064 2112 gca agg agg gaa Ala Arg Arg Giu cga gac ggt att Arg As p Gly Ile aat Asra 695 ata aaa aat gat Ile Lys Asn Asp gat ata Asp Ile 700 tia tta ctt Leu Leu Leu tta ttg aat Leu Leu Asn 720 got Ala 705 gca ggt cgt tta Ala Giy Arg Leu acg Thr 710 tta got aaa gat Leu Ala Lys Asp tat cot aat Tyr Pro Asn 715 ctt att ati Leu Ile Ile 2160 2208 gca atg act ctg Ala Met Thr Leu ctt Leu 725 cot gaa cac ttt Pro Glu His Phe aaa Lys 730 att, ggt Ile Giy 735 gat ggt gaa ttg Asp Gly Glu Leu cgt Arg 740 gao gaa att aat atg ott. ata aaa aaa Asp Glu Ile Asn Met Leu Ile Lys Lys 745 2256 ttg Leu 750 caa tta tot aat Gin Leu Ser Asn gtg too ttg ttg Val Ser Leu Leu gga Giy 760 gtt aaa aaa aat Vai Lys Lys Asn att Ile 765 2304 2352 got coo tat ttt Ala Pro Tyr Phe goa tgt gat att. Ala Cys Asp Ile ttt. Phe 775 gtt otc: tot. tot Val Leu Ser Ser ogt tgg Arg Trp, 780 gaa .gga ttt gga tta gtc gtg gca gaa got atg toa tgt gag cga att 2400 Giu Gly Phe gtt gtt ggc Val Val Gly 800 Gly 785 Leu Val Val Ala Gi u 790 Ala Met Ser Cys Giu Arg Ile 795 ggt gac gat Gly Asp Asp acg gat tca ggg Thr Asp Ser Gly gga Gi y 805 gia aga gaa gtt Val Arg Giu Val at Ile 810 2448 gat ttt ctt gta ccc ata Asp Phe Leu Vai Pro Ile 815 tct Ser 820 gat tea aca caa Asp Ser Thr Gin gca agc aaa att Ala Ser Lys Ile 2496 2544 aaa tig ict ttg Lys Leu Ser Leu cag ata cgt gat Gin Ile Axrg Asp ca c His 840 ati ggt ttt egg Ile Giy Phe Arg aat As n 845 cgt gag cgt att. Arg Giu Arg Ile tta Leu 850 aaa aat ttc tea Lys Asn Phe Ser ata Ile 855 gat act att at Asp Thr Ile Ile atg cag Met Gin 860 2592 tgg eaa gaa Trp Gin Giu etc Leu 865 tat gga act ata Tyr Giy Thr Ile tge tea aaa eat Cys Ser Lys His gaa agg Giu Arg 875 2637 tagatttata tttggaacgt gtcttttgtt tgaatttaat tcaatctcaa ttgagatttt 2697 tgtatttcaa aaataccate atagctaacg atgattggta tttattttaa gatgctttet 2757 ataaatatat tgaegttttt aatgcgeega aaegattggg etgggaaeag agaagtaaaa 2817 etgttttgag aatgaagagt ttttgagatg tttatggata ttaaaaattg ateeagtgaa 2877 ttaattattt ataataaatc aagatttaat gttaatiaat gataatettt. tetgacactc 2937 atattaatta tgagtggtae gtttggtaaa eggtaaacta ttat atg aea get aga Met Thr Alia Arg 880 2993 aca act aaa gtt Thr Thr Lys Val ttg cac Leu His 885 tta eaa tta Leu Gin Leu eca etc tta agt ggc gtt Pro Leu Leu Ser Gly Val 895

3041. caa agg gta Gin A-rg Val tat aea eta Tyr Thr Leu 915 aca Thr 900 tta aac gaa att Leu Asn Giu Ile- a gt. Ser 905 gcg tta. tat Ala Leu Tyr act gat tat gat 3089 Thr Asp Tyr Asp 910 aaa gea tig ctg 3137 Lys Ala Leu Leu 925 gtt tgc tea aaa Val Cys Ser Lys aaa Lys 920 ggt eca eta aca Gly Pro Leu Thr gaa tat gat gtc gat tgt cat tgt atc ccc Giu Tyr 930 Asp Val Asp Cys His 935 Cys Ile Pro gaa ctt Giu Leu 940 acg aga gaa at Thr Axg Giu Ile acc Thr 945 aaa Lys gia, aag aat gat Val Lys Asn Asp aaa. gaa. aaa ttt Lys Giu Lys Phe 965 aaa gca ttg ttc aag Lys Ala Leu Phe Lys 955 ctt tat aag ttc Leu Tyr Lys Phe 3185 3233 3281 gac att gtg cat Asp Ile Val His cat tct tca. aaa His Ser Ser Lys aca ggt Thr Gly 975 att ttg ggg Ile Leu Gly cac act gta. His Thr Vai 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 ate Lys Val Ile 990 aaa aaa, agt Lys Lys Ser cat ggt ttt His Gly Phe tct. ttt Ser Phe 1000 cca gcc gca tct Pro Ala Ala Ser tgg ata gca. aag Trp Ile Ala Lys 1.020 agt Ser .005 3329 3377 3425 tat tac Tyr Tyr 1010 aag tta, Lys Leu 1025 ctt tat ttt Leu Tyr Phe ttc atg gaa Phe Met Giu 1015 ttc ttt acg gat Phe Phe Thr Asp atc gtc ttg aat Ile Val Leu Asn 1030 gta gat gat gaa, tat Val Asp Asp Giu Tyr 1035 ata gca. ata, aac aaa. Ile Al1a Ile Asn Lys 1040 3473 3521 tta aaa ttc Leu Lys Phe aag cgg Lys Arg 1045 gat aaa gtt Asp Lys Val ttt tta Phe Leu 1050 att cct aat gga, gta gac Ile Pro Asn Giy Val Asp 1055 act gat Thr Asp aag ttt Lys Phe 1060 tct cct tta Ser Pro Leu gaa aat Giu Asn 1065 aaa att tat Lys Ile Tyr agt agc ace ttg Ser Ser Thr Leu 1070 3569 3617 aat cta gta atg gtt ggt aga tta tc-c aag Asri Leu Val Met Val Giy Arg Leu Ser Lys 1075 1080 caa aaa. gat Gin Lys Asp 1085 cct. gag aca Pro Giu Thr tta ttg Leu Leu 1090 ctt gct gtt Leu Ala Val gaa aaa Giu Lys 1095 ctg ctg aat gaa aat gtt aat gtt aag Leu Leu Asn Giu Asn Vai Asn Val Lys 1100 gaa cta aaa gaa. cag tta gaa agc agg Giu Leu Lys Giu Gin Leu Glu Ser Arg 3665 ctg aca ctt gta gga gat ggt Leu Thr Leu Vai Giy Asp Gly 3713 1105. 1110 1115 1120 00 ttc aaa egg caa gat Phe Lys Arg Gin Asp 1125 att git aat att tta Ile Val Asn Ile Leu 1140 tgg gag ggt atg cca Trp Giu GlY Met Pro gga cgt Gly Arg aaa gt Lys Val ata att ttt Ile Ile Phe 1130 aat gat ctt Asn Asp Leu 1145 cat gga tgg tca gat aac His Gly Trp Ser Asp Asn 1135 tit ata tta cct tct ct Phe Ile Leu Pro Ser Leu 1150 gca ttg agc tgt gga ct Ala Leu Ser Cys Giy Leu 1155 gtc act Val Thr tta gca att Leu A-la Ile 1160 aat ati cca Asn Ile Pro 11*75 t ta Leu ga a Giu 1165 cca tgt Pro Cys 1170 ggc tat Gly Tyr 1185 caa aaa Gin Lys ata Ile ggt aat aat age Giy Asn Asn Ser 1180 tta Leu ata gaa gat Ile Giu Asp 3761 3809 38 57 3905 3953 4001 4049 aat ggt Asn Gly atc atg Ile Met 1 tgt ttg ttt gaa att aga gat Cys Leu Phe Giu Ile Arg Asp 1190 1195 tea tat gtt ggt aag cca gaa Sex Tyr Val Giy Lys Pro Giu .205 1210 cga tea ttt att ctg aaa aat Arg Ser Phe Ile Leu Lys Asn 1225 gtc aga cag cta tat gat aat Vai Arg Gin Leu Tyr Asp Asn 1240 tgi cag ita ita ict Cys Gin Leu Leu Ser 1200 ctg ait gca cag caa Leu Ile Ala Gin Gin 1215 tat gga tta git aaa Tyr Giy Leu Vai Lys 1230 taaatgaaac: cgaaaagtl tct ace aat gca Ser Thr Asn Ala 1220 aga aat aai aag Arg Asn Asn Lys 1235 t.a 4102 aaaaagaaca cgtaacatct aaaeaatgtc: cgctcaacat cggaagaagt agttcgttga. ggcacggaig gatgggtggg ggtttttcaa gcatiacat aaagcaacag cgaaagccgt tattgccgaa atctcttgaa ctgctattga taataccttc agtgaaaata caagccgeac: atcggcgtcg ggiiataccg aatccaggca acgcctcgtc ttccctgaaa tittaggaca 44 aaattacagt aaccccgegg tcggtatggc ictetattit agaaactggi gcaiccigti ccatatcicg ccattcgtcg tttittatig tgaccaccc agtgatggga caaccgttcc iccttactat aatgggitaa. ataaaggcga taaccgcgag caatgattaa tgacaggagt cgcaaccteg cgtgaaaaga acggtgaaag agcaggtgca taicatcat ctttctgcac 4162 4222 4282 4342 4402 4462 4522 4582 aaggctttac ttcatcggia cc <210> 23 <211> 247 <212> PRT <213> Escherichia coli 4604 <400> 23 Val Asp Asp Asn Leu Lys Gay Gin Gly Ala Gly Lys Asn Phe Leu Ser 1 5 10 Leu Ile Lys Asp Ile Trp Ser Giu Thr Asp Thr Ile Tyr Cys Asp Gin Asp Tyr Ala Asn Leu Glu Asn Lys Ile Phe Giu Leu Val Glu Ile Lys Leu Asn Val Ser Asp Ala Pro Ser Leu Val Tyr Ala Asp Gly Tyr Ala Tyr Met Ser Asn Asn His Al1a Asp 70 Gay Giu Gly Thr Ile Asp Phe Ser Giy Asp Gin Leu Lys Phe Leu Phe Phe Asn Gay Gly Tyr Gin Leu Leu Asn 115 Cys Ser Ile Met Asn Arg Ala Met Thr Lys Phe 110 Ile Thr Thr Tyr Arg Gay Phe Tyr Leu His Asp Asp 125 Leu Ala 130 Ala Tyr Ala Leu Ga y 135 Lys Val Tyr Phe Leu Pro Lys Tyr 140 Gly Ile Lys Thr Leu Pbe 160 Met Leu Tyr Arg Gin 145 His 150 Thr Asn Ala Val Thr 155 Arg Asn Gly Leu Thr 165 Ser Lys Phe Lys Ser 170 Pro Val Asn Tyr Leu Leu 175 Scr Arg Lys His Tyr Gin Val Lys 180 Lys 185 Ser Phe Phe Giu Cys Asn Ser 190 Phe Ile Ser Ser Ile Leu Ser Glu 195 Thr Asri Lys 200 Lys Val Phe Leu Asp 205 00 Phe Cys Giu Set Asn Asn Lys Phe Thr Asp 210 215_ Gly Gly Phe Arg Leu Asn Asn Ser Azg Thr 225 230 Phe Phe Lys Leu Trp Arg 220 Lys Leu Leu Leu Lys Phe 235 240 Leu Ile Arg Arg Lys Phe Set 245 <210> 24 <211> 261 <212> PRT <213> Escherichia cli <400> 24 Met Ile Set Ile Leu 2 Thr Pro Thr Phe Asn 10 Arg Gin His Thr Leu Set Arg Leu Phe Ile Ile Ile Asn Set Leu Ile Leu Thr Asp Lys Asp Phe Giu Trp Leu Val Glu Asp Asp Gly Set Ile 40 Asp Ala Thr Ala Val Asp Phe Arg Lys Lys Cys Phe Asp Leu Ile Tyr Cys Tyr Gin Glu Val Lys Ala Cys Atg Asn Asn Gly Lys Pro Met Ala Leu Asn Ala Gly Asp Tyr Ile Phe Ile Val Asp Set Asp 90 Asp Ala Leu Thr Pro Asp Ala Ile Lys Giu Set Phe 115 Ile Lys Giu Ser Ile 105 His Asp Cys Leu Set Glu Lys Lys Giy Gly Set Gly Val Gly Arg Lys Ala Tyr Ile 125 Ile Ile 130 Gly Asn Asp Leu Asn 135 Asn Ser Set Glu His Ile Tyt Tyr Leu 140 Asp Val Ala Tyr Cys Ala Tht Giu Ile Asn Leu Ile Asri Phe.Lys Lys Giu Set Leu Val Lys Asn Pro Phe Pro Arg Ile Giu Asp 16510 Glu Lys Phe Ala Lys Ile 195 Val 180 Pro Giu Leu Tyr Ile Trp 185 Asn Lys Ile Thr Asp Lys 190 Cys Giu Tyr Arg Phe Asn Ile Ser 200 Lys Val Ile Tyr Leu 205 Leu Asp 210 Asp Gay Leu Set Lys 215 Asn Phe His Asn Leu Lys Lys Tyr Lys Gly Phe Lys Tyr Tyr Lys Asp Axg Lys Arg Giu Lys 240 Thr Tyr Ile Lys Lys 245 Thr Lys Met Leu Ile 250 Arg Tyr Leu Gin Cys Cys 255 Tyr Tyr Giu Lys Ile 260 <210> <211> 368 <212> PRT <213> Escherichia coli <400> Met Lys Ile Leu Phe Val Ile Thr Gay 1 5 Leu 10 Gly Leu Gly Gly Ala Giu Lys Gin Vai Val Lys Ile Leu Leu Ala Asp Leu Set Leu Ser Giy His His Val Phe Pro Ile Ser Leu Gly Met Set Asn Asn Set Giu s0 Asn Asn Val Asn Val 55 Ile Asn Val Asn Met Set Lys Asn Ile Asp Val Ile Ala Asn Set Gly Val Ile Lys Gly 70 Cys Val Arg Ile Arg Phe Lys Pro Asp Ile Val His Ser His Met 90 Phe His Ala Asn Ile Ile Thr Arg Leu S er 100 Val Ile Gly Ile Lys 105 Asn Arg Pro Gly Ile Ile Ser 110 Thr Ala His 115 Asn Lys Asn Giu Gly Gly Tyr Phe Arg 120 Met 125 Leu Thr Tyr Arg Ile 130 Thr Asp Cys Leu Asp Cys Cys Thr Asn 140 Val 5cr Lys Giu Al a 145 Val Asp Glu Phe Leu 150 Arg Ile Lys Ala Asn Pro Ala Lys Ile Thr Met Tyr Gly Ile Asp Thr Lys Phe Lys Phe Asp Leu 175 Leu Ala Arg Ile Leu Leu 195 ALrg 180 Giu Ile Arg Asp Gi y 185 Ile Asn Ile Lys Asn Asp Asp 190 Asp Tyr Pro Leu Ala Ala Gly Leu Thr Leu Ala Lys 205 Asn Leu 210 Leu Asn Ala Met Thr 215 Leu Leu Pro Giu His 220 Phe Lys Leu Ile Ile 225 Ile Gly Asp Gly Glu 230 Leu Arg Asp Glu Asn Met Leu Ile Lys Leu Gin Leu Ser 245 Asn Arg Val Ser Leu 250 Leu Gly Vai Lys Lys Asn 255 Ile Ala Pro Trp Giu Gly 275 Phe Ser Ala Cys Ile Phe Val Leu Ser Ser Axg 270 Cys Giu Arg Phe Giy Leu Vai Val 280 Ala Glu Ala Met Ser 285 Ile Val 290 Vai Gly Thr Asp 5cr 295 Gly Giy Val Arg Glu 300 Val Ile Gly Asp Asp 305 Ile Asp Phe Leu Val Giu Lys Leu Ser 325 Pro 310 Ile Ser Asp Ser Thr 315 Gin Leu Ala Ser Leu Ser Gin Ile Arg 330 Asp His Ile Gly Phe Arg 335 Asn Arg Giu Gin Trp Gin 355 Arg 340 Ile Leu Lys Asn Phe 345 Ser Ile Asp Thr le Ile Met 350 His Giu ALrg Giu Leu Tyr Gly Thr 360 Ile Ile Cys Ser Lys 365 <210> 26 <211> 367 <212> PRT <213> Escherichia coli 00 <400> 26 Met Thr Ala Arg Thr 1 5 Thr Lys Val Leu His Leu Gin Leu 10 Leu Ser Gly Thr Asp Tyr Gin Arg Val Thr Asn Giu Ile Ser Leu Pro Leu Ala Leu Tyr Pro Leu Thr Asp Tyr Thr Leu Val 40 Cys Ser Lys Lys Gi y Lys Ala Leu Leu Giu Tyr Val Asp Cys His Ile Pro Giu Leu Thr Arg Giu Ile Thr Val 70 Lys Asn Asp Phe Lys Ala Leu Phe Lys Tyr Lys Phe Ile Lys Lys Giu Lys Phe Ile Val HIs Thr His Ser Ser Lys Thr Gly Lys Val 115 Ile Leu Gly Arg Ala Ala Lys Leu Ala Arg Val 110 Ala Ala Ser Ile His Thr Val Gly Phe Ser Phe Pro 125 Ser Lys 130 Lys Ser Tyr Tyr Leu 135 Tyr Phe Phe Met Glu 140 Trp Ile Ala Lys Phe Thr Asp Lys Ile Val Leu Asn Val Asp Asp Giu Tyr 155 Ala Ile Asn Lys Leu 165 Lys Phe Lys Axg Lys Val Phe Leu Ile Pro 175 Asn Gly Val Ser Ser Thr 195 Asp 180 Thr Asp Lys Phe Pro Leu Giu Asn Lys .lle Tyr 190 Lys Gin Lys Leu Asn Leu Val Met 200 Val Gly Arg Leu Asp Pro .210 Giu Thr Leu Leu Leu 215 Ala Val Giu Lys Leu 220 Leu Asn Glu Asn Asn Val Lys Leu Thr 230 Leu Val Gly Asp Giu Leu Lys Giu Gin 240 Leu Glu Ser Arg Lys Arg Gin Asp Arg Ile Ile Phe His Giy 255 Trp Ser Asp Leu Pro Ser 275 Asn 260 Ile Val Asn Ile Leu 265 Lys Val Asri Asp Leu Phe Ile 27 0 Glu Ala Leu Leu Trp Giu Gly Pro Leu Ala Ile Leu 285 Ser Cys 290 Gly Leu Pro Cys Ile 295 Val Thr Asn Ile Pro Gly Asn Asn 300 Giu Ile Arg Asp Ser Cys 320 Leu 305 Ile Giu Asp Gly Tyr 310 Asn Gly Cys Leu Gin Leu Leu Ser Lys Ile Met Ser Val Gly Lys Pro Glu Leu 335 Ile Ala Gin Giy Leo Val 355 Gin 340 Ser Thr Asn Ala Arg 345 Ser Phe Ile Leu Lys Asn Tyr 350 Lys Arg Asn Asn Val Arg Gin Leu Tyr Asp Asn 365 <210> <211> <212> <213> <220> <221> <222> <220> <221> <222> 27 1272 Escherichia coi CDs (319) (1269) CDS .(215) <400> 27 cc ggg aag cac tcg gcg ctg att gtt gca cat cgt ctg acc ace gcg Gly Lys Hi-s Ser Ala Le Ile Val Ala His Arg Leu Thr Thr Ala 1 5 10 caa cgc tgc gat ctg att gcc gtt Gin Arg Cys Asp Leu Ile Aia Val tac gga Tyr Gly acc cac gaa Thr His Glu cag ctg tia Gin Leu Leu att gat aag ggg tta cit gcg gaa Ile Asp Lys Gly Leu Leu Ala Giu 25 tct gcg ggc ggc etc tat ace cgc Ser Ala Gly Gly Leu Tyr Thr Arg 40 act gct etc cat cgc cag eac aac Thr Ala Leu His Arg Gin His Asn 143 tta tgg cat Leu Trp, His gac age gtc agc Asp Ser Val Ser ai~g aag Met Lys gag gaa ace ceg Giu Giu Thr Pro gga Gi y tag itaciggaca cgtaatgtat taaaaacaca gtcagaagcg gcggtaccgt. gaatagccgc tttaattatt tatactgaca tccttaattt 305 ttaaagagta tga aig ctg aac atg caa caa cat etc tct. get ate gce 354 Met Leu Asn Met Gin Gin His Leu Ser Ala Ile Ala age ctg ege Ser Leu Arg aac caa ctg gca Asn Gin Leu Ala 90 geg gge cae at Ala Gly His Ile get Al a aac ctt. act gac Asn Leu Thr Asp tte Phe 100 tgg ege Trp Arg gaa get gag Giu Ala Gilu 105 teg ctg aat gt Ser Leu Asn Val cct Pro 110 ett gig aeg eca, Leu Val Thr Pro gaa gga geg gaa Giu Gly Ala Giu gat Asp 120 gag cga gaa gig Giu Arg Giu Val ace ttt ctg Thr Phe Leu 125 ctg aac egg Leu Asn Arg eat cct ctg His Pro Leu gag cac gta Giu His Val 150 ca g Gin 135 ggc gtt tat ctg Giy Val Tyr Leu tgg ege gee ega Trp Arg Ala Arg 130 gig aeg gat aaa Vai Thr Asp Lys 145 gaa. aeg gat ate Giu Thr Asp Ile 160 ggc tee tat teg Gly Ser Tyr Ser 498 546 594 gaa aaa. gga, atg Giu Lys Gly Met atg Met 155 age gee cit c Ser Ala Leu Pro tgg aca Trp Thr 165 cig aca cig egi Leu Thr Leu Arg ta Leu 170 cdc gea agi. tac Pro Ala Ser Tyr ige Cys 175 ctg cig gaa ate ccc ccc ggc act acg get gag aeg ati, gca ctg tee Leu. Leu Glu Ile Pro Pro Gly Thr Thr Ala Giu Thr Ile Ala, Leu Ser 185 190 gga ggc egt tt Gly Giy Arg Phe acc ctt gcc gga Thr Leu Ala Gly gcc gat ccg eta Ala Asp Pro Leu aac aaa Asn Lys 210 '738 786 ai~g ccg gag Met Pro GiU ate Ile 215 aac gtt cgg gga Asn Val Arg Gly gca aag gaa tca Ala Lys Giu Ser gtg ctg aca Val Leu Thr 225 ct gat Leu Asp gga caa Gly Gin 245 aaa Lys 230 get ccc gee ctg A-1a Pro Ala Leu tcg gaa Ser Giu 235 tgg aac ggc Trp Asn Gly ggc tic cac ace Giy Phe His Thr 240 aaa tet. ego cag Lys Ser Arg Gin ctg ett ace tcc Leu Leu Thr Ser atg Met 250 cgc ati ate gcc Arg Ile Ile Ala 834 882 930 978 gtt Val 260 cgg etc tat att Arg Leu Tyr Ile gat gtt gat at Asp Val Asp Ile cag ccc etc ggg Gin Pro Leu Gly ctg Leu 275 gte gig ctg cOO Val Val Leu Pro gat ASp 280 ggt gaa ace tgg Gly Giu Thr Trp gat cac ctt ggc Asp His Leu Gly gta tge Val Cys 290 gcg gca atti Al1a Ala Ile gta ctg ggc Vai Leu Gly 310 gao Asp 295 gee gee ata aat Al1a Ala Ile Asn aat Asn 300 ggg cgc ate gtg Gly Arg Ile Vai coo gtg got Pro Vai Ala 305 gag ata etc Glu Ile Leu 1026 1074 att gao aac att Ile Asp Asn Ile gaa eat gaa Giu His Glu oge act Arg Thz 320 ggc ggg Gly Gly 325 ego age aaa otg Arg Ser Lys Leu aag gat ate gee Lys Asp Ile Ala cat ctg ctg cog His Leu Leu Pro a tg Met 340 att ce get gaa Ile Arg Ala Giu caa Gin 345 ecg cag ogt cag Pro Gin Arg Gin gca gac cgt tcg Ala Asp Arg Ser 1122 1170 1218 aca gtg cig Thr Val Leu gee ggg Al1a Gi y 360 cag age etc ggc Gin Ser Leu Giy ggg Gi y 365 ate agi gog eta Ile Ser Al1a Leu atg ggg met Gly 370 get egi tac gca cog gaa aeg tto ggt ctg gtg etc ago cac tot cot Ala- Arg Tyr Ala Pro Giu Thr Phe Gly Leu Val Leu 3cr His Ser Pro 1266 375 38038 385 caa tgc 1272 Gin <210> 28 <211> <212> PRT <213> Escherichia coi <400> 28 Gly Lys His Ser Al1a Leu Ile Val 'Ala 1 5 Arg Leu Thr Thr Ala Gin ALrg Cys Asp Gly Thr His Leu Ile Ala Val Ile Asp 25 Lys Gly Leu Leu Ala Giu Tyr Thr Axg Leu Giu Gin Leu Leu Ala Gly Gly Leu Trp, His Asp Ser Val Ser Ser 55 Tkir Al1a Leu His Arg Gin His Asn Met Lys Glu Glu Thr Pro <210> 29 <211> 317 <212> PRT <213> Escherichia ci <400> 29 Met Leu Asn Met Gin Gin His Leu Ser Ile Ala Ser Leu Arg Asn Gin Leu Ala Al1a Glu Ser Gly His Ile Ala Asn Leu Thr Asp Phe Trp Azg Giu Leu Asn Val Pro Leu 40 Val Thr Pro Val Giu Gly Ala Giu Asp Giu Arg Glu Val Thr Phe Leu Trp Arg Ala His Pro Leu Gin Gly Val Tyr Leu Arg Leu 70 Asn Arg Val Thr Asp Lys Giu His Val Lys Giy Met Met Ser a Leu Pro Glu Asp Ile Trp Thr Leu Thr Leu Axg Leu Pro Pro Gly 115 Pro 100 Ala Ser Tyr Cys Ser Tyr Ser Leu Leu Giu Ile 110 Gly Arg Phe Thr Thr Ala Glu Thr 120 Ile Ala Leu Ser Ala Thr 130 Leu Ala Gly Lys Ala 135 Asp Pro Leu Asn Lys 140 Met Pro Giu Ile Asn Val Arg Gly Asn 145 Pro Ala Leu Ser Glu Lys Glu Ser Val Leu Thr Leu Asp Lys 155 Trp Asn Gly Gly Phe 170 His Thr Gly Gin Leu Leu 175 Thr Ser Met Ile Pro Asp 195 Arg 180 Ile Ile Ala Gly Ser Arg Gin Val Arg Leu Tyr 190 Val Leu Pro Val Asp Ile Ser Pro Leu Gly Leu Asp Gly 210 Glu Thr Trp Phe Asp 215 His Leu Gly Val Cys 220 Ala Ala Ile Asp Ala 225 Ala Ile Asn Asn Giy 230 Arg Ile Val Pro Val 235 Ala Val Leu Gly Ile 240 Asp Asn Ile Asn His Giu Arg Thr Ile Leu Gly Gly Arg Ser 255 Lys Leu Ile Glu Gin Pro 275 Lys 260 Asp lie Ala Gly Leu Leu Pro Met Ile Arg Ala 270 Val Leu Ala Gin Arg Gin Trp Ala 280 Asp Arg Ser Arg Thr 285 Gly Gin 290 Ser Leu Gly Gly le 295 Ser Ala Leu Met Ala Arg Tyr Ala Pro 305 Glu Thr Phe Gly Leu 310 Val Leu Ser His Ser Pro Gin 315 <210> <211> <2 12> <213> <220> <221> <222> <220O> <221> <222> 4039 DMA Escherichia coli CDS CDS (370)..(1326) <400> cct tca Pro Ser 1 aig tgg tgg M!et Trp Trp 5 acg cca gaa aga Thr Pro Giu Arg a cc Thr 10 agt cga cca ggc Ser Arg Pro Gly tig ttc Leu Phe is agc gaa acc Ser Giu Thr ccg cag ggc Pro Gin Gly acc tca tgg gtg Thr Ser Trp Val agt Ser gag cat ctg ctt Giu His Leu Leu tct gcc cca Ser Ala Pro gaa ggt tcg Giu Giy Ser 96 144 gta cgt atc agc Val Arg Ile Ser tgc gtg gga teg Cys Vai Gly Ser ctg Leu aca gtg Thr Vai cct cac gii cag Pro His Val Gin cit cac cag cgg Leu His Gin Arg att acc gct ggc Ile Thr Ala Gly gat tac gca tgg Asp Tyr Ala Trp gic Val gaa agc cat tgc Glu Ser His Cys gea Ala 70 atc tac acc ggt Ile Tyr Thr Gly ggt cac Gly His 75 192 240 285 tgg cgc ggt gca Trp Arg Gly Ala ctg at Leu Ile gac ggg att Asp Gly Ile ggt Gi y 90 tta cta cag ggt tga Leu Leu Gin Gly gttgacccac aaacacittc aggaaacggt acagacttcc tgaataaatc aaatagtcac 345 ctgcggaaaa ggaataatca tcag atg tat gcc cgc gag tat cgc tca aca 396 Met Tyr Ala Arg Glu Tyr Arg Ser Thr 100 cgc ccg cat aaa gcg ati ttc tt cat cit tot tgc ctc acc cit atc 444 Xrg Pro His Lys Ala Ile Phe Phe His Leu Ser Cys Leu Thr Leu Ile 105 110 115 120 00 tgt agt gcg caa Cys Ser Ala Gin tat gcg aag Tyr Ala Lys ccg gat Pro Asp 130 aig cgg eca ctg Met Arg Pro Leu ggg ccg Gly Pro 135 492 540 aat ata gee Asn Ile Ala gat Asp 140 aaa ggc tec gtg Lys Gly Ser Val tac cat ttc agc Tyr His Phe Ser gte acc tct Val Thr Sex 150 acg gec gtg Thr Ala Val tic gac Phe Asp ccg aat Pro Asn 170 ict Ser 155 gtc gat ggc aca Val Asp Gly Tb: egc Arg 160 cat tat cgg gta His Tyr Arg Val tgg Trp 165 aca ace gca ccg Thr Thr Ala Pro teg ggt tac ceg Ser Gly Tyr Pro tia tat atg ct Leu Tyr Met Leu gac Asp 185 ggt aae gca gtt Gly Asn Al1a Val atg Met 190 gai ege cig gat As p Arg Leu Asp gaa ctg etc aaa Glu Leu Leu Lys ca a Gin 200 tig tea gaa. aaa Leu Ser Giu Lys a ca Thr 205 ceg eca. gig ate Pro Pro Val Ile get gte ggg tat Ala Val Gly Tyr eag ac Gin Thr 215 aac etc cci Asn Leu Pro gea gaa age Ala Giu Ser 235 te Phe 220 gat etc aac age Asp Leu Asn Ser agg Arg 225 get tac gae tat Ala Tyr Asp Tyr acg eca gea Thr Pro Ala 230 age egt aag Ser Arg Lys aga aaa aca. gat Arg Lys Thr Asp etc Leu 240 cac tea ggg egi His Ser Gly ALrg tt Phe 245 agt ggt Set Gly 250 gge age aac aac Gly Ser Asn Asn te Phe 255 ege eag tia. etg Arg Gin Leu Leu gaa Giu 260 aeg egt ait gc Thr Arg Ile Ala aaa gtg gaa cag Lys Val Giu Gin cig aat ate gat Leu Asn Ile Asp egg Arg 275 eaa egc cgc ggc Gin Arg Arg Gly tgg ggg cac tee tac Trp Giy His Set Tyr 285 ggc ggc etc tic Gly Gly Leu Phe gig Vai 290 cig gat tee tgg Leu Asp Ser Trp ctg tee Leu Ser 295 tee tet tac Set Ser Tyr tc Phe 300 egg teg tac tac Arg Set Tyr Tyr age S er 305 gee age ccg Ala Ser Pro teg tig gge aga Set Leu Gly Arg 310 1020 ggi tat gat get ttg eta age cgc gtt acg gcg git gag cci cig caa Gly Tyr Asp Ala Leu Leu Ser Arg Val Thr Ala Val Glu Pro Leu Gin 1068 00 tie tgc Phe Cys 330 gat aac Asm As n aaa cac cig Lys His Leu geg Al a 335 gct Al a 320 ata aig gaa Ile Met Glu gte ggg gig Val Gly Val ggc teg geg Gly Ser Ala 340 ctg tcg aaa Leu Ser Lys egg gaa, aeg Arg Glu Thr 345 a cc Thr cat His 350 a aa. Lys aca cag ggt Thr Gin G2.y att cat ac Ile His Thr 360 ttt tgg gat Phe Trp Asp 355 aat Asn etc act ata Leu Thr Ile tic ccc aac Phe Pro Asn cig Leu 380 cig Leu 365 gga Gi y gat aaa, ggc Asp Lys Gly gte Val 370 tic Phe gee gia Ala Val cac ggg ceg His Gly Pro aig Met 385 aat gcc tcc Asn Ala Ser 375 tii egc cag Phe Arg Gin 390 gca. ggt tgt Ala Gly Cys 1116 1164 1212 1260 1308 gCa ctg tia. gat atc Ala Leu Leu Asp le 395 cat gag tia age cac His Glu Leu Ser His 410 agt ggt gaa aac gea. aat tac aca. Ser Gly Glu Asn Ala Asn Tyr Thr taa, acactgcccg etttiacgcg ggcagtacgc 1356 ctgaaacact tiataggiat ccgacatiaa taagcgccea gia egcggt aiggiecagi gigiettti ttca ccagtg tgccacttga atcttattet acgatcagaa tegeccete gacgcagatt gctctttaCe ttgictgee taagcgagtt gctecgaa gt ggaaagacat ggatatatgc ggtaatcatt tgatgcggta agaagategg tttatiaata. tgacagaceg atataacgtc attgatagta. gateatccat. actggcibeg gcctgaagcg gcggaagtag acteeggcat aagatctgtt tcgtaattga. ccagiatitt cagitgacgc tatttcggga gtggcattgg ataccgteca gtttgcccga gtcacacttg agtaagcccg tattgaggat aqttcgtccc cacigcgggt tggcagaaaa tgaccgacag taticcagt ccagagcttt taacgttatc cgtggtaate geciggeteg 1416 attactgaeg 1476 caccagtgaa 1536 ticcgcatga. 1596 cgcctgggtg 1656 aggattaceg 1716 cagacgatct 1776 cccgccatte 1836 cccggccaeg 1896 tieccaggtg 1956 aactccagcc aggtagcacc tagccttcac actttgaaat gagtcgctga atgitatctt gcagagccag tcatcgagct ttcaaaggaa ttttcacccg ttattggttt tgcgtaatgc gcttttcggt gcggctatat gccgttaata agaattaata aagagcatta atcgctactt acgtitggta a gggccgcgg gcgggtatca accatcaatt gttaccgcgt caatttcttt cgcctgatgt tggattgata aatcgcccaa gataatcaaa caatatacag aaataccgct tatcgcggtt tattaagctc ctaaaatacg tctcgtaata cataattctg aactgcactg ccggcttcga tctttgttac tcccaactgt ccagccagag tccggctgat atgatgttca atcacttcaa cgctctccac aaaattaagg gtgcccgagg attgacgctg aatatctttt caggtttggg ttcctgcgaa gcgcaggccg cgcactgatt gatatcactg ccactctgca gccgctggtt cccttcacca aacaccaaag tcggtacagg gaagaactgt aatcgagaat gtaccccttc cagcatccgt gcccactaag tggtgtataa ccaccccccc tacgctcaac gccagctata tgttttctgg cgctattgcc atttccggat ggacagccat gctttaaagg agattcagac ggaatgatat tgagaatgat tcattcaccg ccaacggtca cgccaggaac ccgccggata cgactttgte cggctcgtct tttgcgtatc cigctgcgga atgcccggct tttattcaga gctgaaattg cgacagcgaa ggctgccccc ctgttccggt acgcacggag ccccatacca ggtaagattg ctttttaata cgagatcttt tgcctttcga ttcgggcaac tggggctgaa tcgtgccagg ttttactgct tcaggctggt gcgtitgatc tcaggcgatt atccttcatt cccagtceca cttgtgccgg gccgcataga tttaatttcc gcgtttiicg ttaccataca gcgcgacgcg ccgtgccagt gaaccgtagc ggcaccca gt ttacgtgacg. cgaatatcga acgccaggca tcctcgctgg attaccgatc gtagagcaga ccctgctttg gttcccgccg aaccggctca gcgatccgca agaggaagga aaccatcaca ggtcgtaaac catgcgggta gataccatta attttgccag ta ttcccctg acgagacaac taccgaccgg aacgcgtggt tagcgccctc cgttggtggg gcgccgccgc tggtgtcacc tcaccggtac tctggcggtt ttttacgaat taataaccga 2016 2076 2136 2196 2256 2316 2376 2436 2496 2556 2616 2676 2736 2796 2856 2916 2976 3036 3096 3156 3216 3276 3336 3396 aatatctgaa aggtcgttta ccggaggggt cacgcccggc attatcatcg agttagcgac aaaatgittg ttataiaaga aatataicga tacttcagtc actcattccg ggtgcgctig tttctaacct gtctttctgc tgctgtttta icggaggatt cagaggattt atcgttaagc atgataatta tttttcataa aaataaattt gcaaagtcag icgatcatcg gcattttcag aacactactg atacctgctc tggctactga tgttaattct tcacatcctt atatcattta atatcaaatt ctgaagcact taccgttcat ggaatttigt acacgggcgc ctttcaacaa agcggtggct tacctggcta catacctatt gccagatatt gcaaaagaaa gataiataac gctagtagtg cttttgtact cacaatttct tgcttatgta ggtcaggcat tccaccacca ttcaacccaa ccctaataaa ttttactgcc aagcaatccc atatgttttt ccagttcagc gatgttgcca aacggatagt tataagatca ttc gagtctcgtc ccaggagcac tgcctaactt attattgttt tcacaagata tatticattg tttctttttg ctggaaaatc gttcacattg gcatcactag 3456 3516 3576 3636 3696 3756 3816 3876 3936 3996 4039 <210> 31 <211> 94 <212> PRT <213> Escherichia coli <400> 31 Pro Ser Met Trp Trp Tku 1 5 Ser Glu Thr Asp Thr Sej :Pro Giu Arg Thr 10 Giu Ser Arg Pro His Ireu Lieu Trp, Val Val Ser 25 Cys Gly Leu Phe Ser Ala Pro Glu Giy Ser Thr Ala Gly Pro Gin Gly Thr Val Pro A.rg Ile Ser Val Gly Ser Lieu Ile His Val Gin Vai Giu Gin Ile His Gin Arg Ser His Cys Trp Ala 70 Ile Tyr Thr Gly Gi y Leu Asp Tyr Ala Arg Gly Ala Asp Gly Ile lieu Gin Gly 00 <210> 32 <211> 318 <212> PRT <213> Escherichia coli <400> 32 Met Tyr Ala 1 Phe.His Leu Lys Pro Asp Arg Glu Tyr Arg Ser Thr Arg Pro His Lys Aa Ile Phe Ser Cys Leu Thr Leu Ile 25 Cys Ser Ala Gin Val Tyr Ala Lys Gly Ser Met Arg Pro Leu Gly 40 Pro Asn Ile Ala Asp Val Phe Tyr His Phe Ser Val Thr Ser Phe Asp Val Asp Gly Thr Arg His Tyr Arg Val Thr Ala Val Pro Asn Thr Thr Ala Pro Ser Gly Tyr Pro Ile Leu Tyr Met Leu Asp 90 Gly Asn Ala Val Met Asp Arg Leu Asp Val Ile Val 115 Asp 100 Glu Leu Leu Lys Leu Ser Giu Lys Thr Pro Pro 110 Asp Leu Asn Ala Val Gly Tyr Gln 120 Thr Asn Leu Pro Phe 125 Ser Arg 130 Ala Tyr Asp Tyr Thr 135 Pro Ala Ala Glu Ser 140 Arg Lys Thr Asp Leu His Ser Gly Arg 145 Arg Gin Leu Leu Glu 165 Ser Arg Lys Ser Gly 155 Gly Ser Asn Asn Thr Arg le Ala Lys Val Giu Gin Gly Leu 175 Asn Ile Asp Leu Phe Val 195 Arg 180 Gin ALrg Arg Gly Leu 185 Trp Gly His Ser Tyr Gly Gly 190 Phe Arg Ser Tyr 205 Leu Asp Ser Trp Leu 200 Ser Ser Ser Tyr Tyr Ser Ala Ser Pro Ser 210 Leu 215 Gly Arg Gly Tyr Asp Ala Leu Leu Ser 220 Arg 225 Val Thr Ala Val Pro Leu Gin Phe Al1a Lys His Leu Al a 240 Ile Met Giu Giy Ala Thr Gin Gly Asp 250 Asn Axg Glu Thr His Ala 255 Val Gly Val Lys Gly Val 275 Leu 260 Set Lys Ile His Thr Leu Thr Ile Leu Lys Asp 270 Gly His Gly Asn Al1a Val Phe Trp 280 Asp Phe Pro Asn Pro Met 290 Phe Asn Ala Set Arg Gin Al1a Leu Asp Ile Ser Gly Glu Asn Ala Asn Tyr 305 Thr 310 Ala Gly Cys His Gi u 315 Leu Ser His <210> 33 <211> 3292 <212> DNA <213> Esckerichia cli <400> 33 ccgctgcggt attcaataaa aggcagaict tttttcagga tggcgcacgc cccgccgttt taaggttgct ccgttgagga gatgtctggt ccaggatgcc tcagatttac ccttcccatg gcttccggac tccagtgctt gaggtgcgcg ccgcgagtgc ttaacgccat gcaatggctt tttggatgt cgccattcgg ttctgcggct tagccctgat tgattgccgg ttgcagcgtt cagcgatagc tctccatata cgatagagtc gcattactgt gaatcaggac agtagtgctc ccacaccatc ccgccagatc gcggttggat tagaaccttt cgttatcaga tatacagatt ccggagagct cgtaatagag attecatcca cctgttcacc attcagaacg tatacatatc gcgactcttt cgtgcagcaa atgcggcgtg ctgtaggctg gccggcttag cgcgtgcatt gctttcctgc gccggtgaat gtgatacttg ggccttacgg gataaaggtg cagcgccgta catgcctttc cgcaccgcgg ggtgaacaca ggcgaagata acccgcatat gaagaaaggc gcgttga tc gccgcgcacg agccgggctc ggacaccgag gttttccccc ctgcggcagc aacgccttat gataagatgc tcagatttaa tcggtctgta ggatcggtgt ccaccctgat aactcatcca ttagactgac gttttcggta gggaagagat cagtaaacga aacggcgtgc atcagcgtgt tcgttcatct ttggcgttcg ttatcactct aggtcttcca gcatgaacgt agggcgactt ttaaagccgc atatgccatt gtggttaacc ccggcctaca gtcagcatcg tctgcgcgcg g cggta cacc acaggttaaa atccgctctg tacgcacagc catttgttcc ctaaattcgc ccgccagatc a ggttggcac gaccgtgcgg tatcaagctg ccaccatgca ggtagttatc tcgccatctt tatatttcgg catctttgct ccgggttgac ggaaatcatc tcccgatagc cttgcagacc atcattgcaa caiccggcaa tggtggatat catcggaata caccgacgat ggtataagcg agaaagttta caggaagaaa tactttcgcc gacaatgccg acgaacgccg cggaacttcg accgtttttc gtcgccgtaa gaagtgacag gtcgaggaac cgtaatgtcg gaacggcagt atgaacatca aaagccaacg ctgggtgacg gcccggttgc 120 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 ccgtacattg gcgcgggtig gcaacggcgt acgtccatcc tttttctcaa accggcatca tcgtatccgg atgagaggaa atgcaaaatg agatccctct ttatccagaa gatattgtaa ggcattaata aattgtgcgc cagaattate aacgagtaga gacgcagagc acaccatgga gcctgctccg gcctccgggt cgcgacgcat atgcgtaatc cctgccatic cgcccacgtt gttttcagac atcgatgata tgccacctgc caaaccttca ttccagcatt atccagcagc ttccggatgg ttcattacgg gcggcaicag gggaagaact cgaiatctgg agcccacatc gttccgccag tgttgtcggc caaagccttt gagctgcggc ctccggtttc ccctgacagg atgaattgaa ggcggtgatg tatatgttat aggagaaata tcataacaag tgctcattcc cgtttacggt cacaacgttg taataagagc gagaaagagc cgctgcggct gtaggcgtcc tccgtgtttc tttgatctgt gccggggatc atttgciggg aaggccacct ctaccgttat gcacgatgtt gaactccatg cgtggcgtaa gccagttgca aatgccgtgg cggttgagaa tgtagggtta atccagcaag tttctgcigg aatagtggtc gcgtgcggtg gacagcaaca aigtcgtcaa atgattgcat aaatcaggag ttatatcgcg taaitgaatg ttcactcagg tgttaaggga atctcttatg gcttatcgtc agtgaagcac aggcgttttt tactgtggcg tcttccggct ggacgttgtt atcagcgact tggcgcagea ggcagcagca cagtatcatg gatgacgcgt cggcacgcgc cttcatcacc caccagtgcg cttccagcag gacgtacacg tggatggagt tacgccgaag cccaccgcca aaaacaacca gtttctttgt gccggtttaa gcggttgacg acaagaagtt aatgatgacg aaataatagt agcattttca ttgattattg acttttatta aagttattac tgttatttcc ttcgccttag cactgacaga ccacttgttg ttatatatca ggttgttctg tgtgcagtct tcagcgctgc gacccagtgt ctttticcaa ggccgaatcg atcgtcacac tttccggctt ctgatccatc aacatgggct gatatacgcc cttatccacg ggtgatttct attgtccggt ttaaaatcag cgccgccgcc cgttcggttt cttgtgcagg ccagatactg gggtatctgc tgggtgaaaa taattaagca gataaaaata atcctacctc atgctgtttt ttcattatat tcaggaagca cggttctctg tgcctcataa tgtcgcttat tcatacagac gaaaggcccc caacgttaac gtccagcgcg gcggaaggcg gctccacaac gctgttcccg tcatactggc tcaataagat tggtttttcc aggccaatcc ttcgccattg tgttccgcca ccgtgacgtg accggaatgg gagaaicgtg cccctggctg gttaaagcca cttaccggtt atgctgcatc gtttgggtga tgcgctggct cgaaaattcc ttgataattg aattatttat tggcgcaggt tagttttaac atatgtgtag aagaggatta tggcataata actccggaat gcctcatcag ctgttttaac ggaggtgctt atcaaaccgt tcggcaagcc agcgatgctt agcgggcgat ggttaattgg gtttcaggcc gttccgccat accagttacg atgcctgttg atgggatgat gacgtaatac ctgcatggtt tgtcattgcc 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3292 ggccagctcc gctgcgcgtt ccagatgttg gttggcgcgt grcttcagcat cc <210> <211> <212> <213> <220> <221> <222> <220> <221> <222> 34 11165 DNA Escherichia coli CDs (3791)..(4834) CDS (10459) (10776) <220> <221> CDS <222> (10134) .(10427) <220> 00 <221> CDS <222> (9836).. (10081) <220> <221> CDS <222> (7816).. (9480) <220> <221> CDS c-I<222> (4878).. (7802) <220> <221> CDS <222> (3460).. (3702) <220> <221> CDS <222> (3054).. (3407) <220> <221> CDS <222> (2613).. (3041) <220> <221> CDs <222> (2198).. (2530) <220> <221> CDs <222> (1939) (2196) <220> <221> CDS <222> (1573) (1893) <220> <221> CDS <222> (1102) (1485) <220> <221> CDs <222> (2)..(1099) <400> 34 c agc gat aig cag cgc ggi atc cag get gca acg get gca cit cag ggc 49 Ser Asp Met Gin Axg Gly Ile Gin Ala Ala Thr Ala Ala Leu Gin Gly cig gig ggc Leu Val Gly gag cig gcg GJlu Leu Ala aat atg gca ggc Asn Met Ala Gly geg Al a cig gca ggt get Leu Ala Gly Ala tca gcg ccg Ser Al1a Pro gac aat aca Asp Asn Thr aac atc ate ggt Asn Ile Ile Gly cat His cac gcg gg't ati His Ala Giy Ile geg gca Al a Ala s0 aaa gec att gcc cat gee att etc ggi Lys Ala Ile Ala His Ala Ile Leu Gly gig aca gca gee Val Thr Ala Ala cag ggc aac agi Gin Gly Asn Ser geg Ala gca gca ggc gca Ala Ala Giy Ala ati Ile ggi gcg ggt act Gly Ala Gly Thr 241 289 gaa gig ate gcg Giu Val Ile Ala gcc att gcg aaa. Ala Ile Ala Lys etc tac ceg gge Leu Tyr Pro Giy gta. gat Val Asp ccg tcg aaa Pro Ser Lys acg ctg tca Thr Leu Ser 115 aca gaa. gat cag Thr Giu Asp Gin aag Lys 105 caa act gia Gin Thr Val age aeg ctg gca Ser Thr Leu Ala 110 ggc gat gig get Gly Asp Val Ala 125 gcg ggt aig gee Ala Gly Met Ala ggc Gi y 120 gge ati gcc agi Gly Ile Ala Ser ggc geg Gly Ala 130 get get gga get Ala Ala Giy Ala ggt Gi y 135 gee ggg aag aac Ala Gly Lys Asn git gtt gag aai aat Val Val Giu Asn Asn 140 gca gca cct tge agg Ala Ala Pro Cys ALrg geg Al1a 145 cig agi cig gt Leu Ser Leu Val aga ggc tgt geg gte Arg Gly Cys Ala Val 155 act aaa git gca Thr Lys Val Ala gee ggg cit gcc Ala Giy Leu Ala 180 gag Glu 165 cag tig eta gaa Gin Leu Leu Glu ate Ile 170 ggg geg aaa geg Giy Al1a Lys Ala gge aig Gly Met 175 ggg geg gca gte Gly Ala Ala Val aag Lys 185 gat aig gee gac Asp Met Ala Asp agg atg ac Arg Met Thr 190 icc gat gaa ctg gag cat cig ait. acc ctg caa atg aig ggt aat gat Ser Asp Giu 195 Leu Giu His Leu le 200 Thr Leu Gin Met Met 205 Gly Asn Asp gag atc Giu Ile 210 act act aag tat Thr Thr Lys Tyr ctc Leu 215 agi tcg ttg cat Ser Ser Leu His aag tac ggt tcc Lys Tyr Gly Ser ggg Gi y 225 gct gcc tcg aat Ala Ala Ser Asn ccg Pro 230 aat atc ggt aaa Asn Ile Gly Lys ga t Asp 235 ctg acc gat gcg Leu Thr Asp Ala 673 721 769 aaa. gia gaa ctg Lys Vai Giu Leu ggc ggt Giy Giy 245 icc ggc tca Ser Giy Ser acc ggt aca cca. Thr Giy Thr Pro eca cca Pro Pro 255 tcg gaa aat Ser Giu Asn aat cag aag Asn Gin Lys 275 cci. aag cag caa Pro Lys Gin Gin aat Asn 265 gaa. aaa act gta Giu Lys Thr Vai gat aag ct Asp Lys Leu 270 act ata aaa Thr Ile Lys caa gaa agi gcg Gin Giu Ser Ala aag aag atc gat Lys Lys Ile Asp aac Asn 285 aat gct Asn Ala 290 cig aaa gat cat Leu Lys Asp His gat Asp 295 ait att gga act Ile Ile Gly Thr aag gat atg gat Lys Asp Met Asp gat cat atg cag Asp His Met Gin 320 ggi Gi y 305 aag cca git cci Lys Pro Vai Pro gag aat gga gga Giu Asn Gly Giy tat tgg Tyr Trp 315 913 961 1009 gaa aig caa aat Giu Met Gin Asn acg Thr 325 cic aga gga. ita Leu Arg Giy Leu aai cat gcg gat Asn His Ala Asp acg tig Thr Leu 335 aaa aac gic Lys Asn Val gai gct ati Asp Al1a Ile 355 ati acc tta Ile Thr Leu 370 aac Asn 340 aat cci gaa gct Asn Pro Giu Ala cag Gin 345 gCt gcg tat ggc Ala Ala Tyr Gly aat aaa ata, gaa Asn Lys Ile Giu tca Ser 360 gcc ttg aaa gga Ala Leu Lys Gly tat Tyr 365 aga gca aca Arg Al1a Thr 350 gga. at atg Giy Met aaa, gag cct Lys Giu Pro 1057 1104 cgt. Arg aaa. tig Lys Leu att gga aac atc Ile Giy Asn Ile 375 aat atg aca Asn Met Th~r 380 1152 gag eaa Giu Gin 385 caa tea ccg ct Gin Ser Pro Leu etc tgg tte gaa Leu Trp Phe Giu ate ata gat gig Ile Ile Asp Val 1200 cit gaa aag tta aca gig gaa gat ct Leu Giu Lys Leu Thr Val Glu Asp Leu 405 tge Cys 410 cge gct aic cga Axrg Al1a Ile Arg caa Gin 415 1248 aat tta tgt at Asn Leu Cys Ile ga t Asp 420 cag itg atg cca Gin Leu Met Pro gig ttg gaa gt Val Leu Giu Val eta act Leu Thr 430 1296 aaa gag ccg Lys Glu Pro ita tea acg Leu Ser Thr 450 ita Leu 435 gcg ggt gaa tat Ala Gly Giu Tyr tac Tyr 440 gat ggt gaa eta Asp Giy Giu Leu ait gea get Ile Ala Ala 445 agi aec tt Ser Th: Phe 1344 1392 ata aaa gga gaa Ile Lys Gly Giu Cta aaa gat cag Leu Lys Asp Gin acc eaa Thr Gin 465 ata agg caa ct Ile Arg Gin Leu ata Ile 470 aac cag eta gaa Asn Gin Leu Giu ccg tea gat ait aae Pro Ser Asp Ile Asn 4.75 cag ata att. gta Gin Ile Ile Val 1440 1485 gat Asp 480 gat tta aga aaa Asp Leu Arg Lys gat Asp 485 ata tta aaa atc Ile Leu Lys Ile aat Asn 490 taaciaaiec cggccactga gccgagatet tctttgtgtg cegggeatgt. tcagcageit 1545 gggggtgaaa gtcceetgte eagectg atg gig geg aag gcg tic geg tac gea 1599 Met Vai Ala Lys .Ala Phe Ala Tyr Ala 495 500 ctt. aac Leu Asn 505 cag tgg ccg gca Gin Trp Pro Ala ctg Leu 510 acg tac tat geg Thr Tyr Tyr Ala aac Asn 515 gat ggc tgg gig Asp Gly Trp Vai 1647 1695 gaa Giu 520 ate gac aae aac Ile Asp Asn Asn get gaa aat gee Ala Giu Asn Ala ctg Leu 530 egg geg gte agt. Axrg Ala Vai Ser ggt egi aaa aae tte etg tie tic ggc Gly Arg Lys Asri Phe Leu Phe Phe Giy t Ser 545 gac eat ggt ggt Asp His Gly Giy gag egg Giu Arg 550 1743 1791 gga geg eta ctg iae age etg ate ggg acg tgc aaa cig aat gac gig Gly Ala Leu Leu Tyr Ser Leu Ile Gly Thr Cys Lys Leu 555 560 gat cca gaa agc tac ctt egc cat gtg ctt gee gte ata Asp Pro Glu Ser Tyr Leu Arg His Val Leu Ala Val Ile 570 575 580 Asn Asp Val 565 gca gac tgg Ala Asp Trp gca etg cca Ada Leu Pro 1839 1887 ccg gtc Pro Val 585 get gaa Ala Giu 600 atg tct Met Ser 605 aac cgg gtc agc gaa ctg ctt ccg tgg cgc aia Asn Arg Val Ser Giu Leu Leu Pro Trp Ax; Ile 590 595 taacacatce ccgtcaatac ggccctcgct gtacgcttac agaaa atg ct; 1944 Met Leu gta cag aaa gaa Val Gin Lys Giu aag Lys 610 aac gte gca gag Asn Val Ala Glu gtg gta tet gaa Val Val Ser Giu acg Thr 620 cat ace ggc gac His Thr Gly Asp age Ser 625 gta tat get tee Val Tyr Ala Ser ttt gaa aaa att Phe Giu Lys Ile 1992 2040 2088 ctg aat ccg gta Leu Asn Pro Val gee ctg agt gea Ala Leu Ser Ala gat aac cet ttc Asp Asn Pro Phe egg tea Axrg Ser 650 gea gat aac Ala. Asp Asn geg Ala 655 act gge aga att Th~r Gly Arg Ile ac Thr 660 tee age ata caa Ser Ser Ile Gln eet geg gtg Pro Ala Val 665 egg eaa. tee Arg Gin Ser 2136 cag tgc Gin Cys cc; tgt Pro Cys 685 get get gea gca Ala Ala Ala Ala act Thr 675 gag ggt tct tgt Glu Gly Ser Cys ccc Pro 680 2184 tea gga a at; gtg gat aae tgg eag aag agt gta agg agt cgt 2233 Ser Gly Met Val Asp Asn Trp, Gin Lys Ser Val Arg Ser Ar; 690 695 gcg Ala 700 etc cc; gaa gag Leu Pro Giu Giu geg Al a 705 at; acg ggc tgg Met Thr Gly Trp aac Asn 710 gaa ggc atg ate Glu Gly Met Ile ege 2281 Ar; 715 tta. eag cag ttg Ljeu Gin Gin Leu get Ala 720 gag egc etg aac Glu Arg Leu Asn cgt ALrg 725 cag gat gaa eag Gin Asp Glu Gin egg gga Ar; Gly 730 2329 aaa.tac atg aeg gte agt gaa, ct; aaa aeg gag gtg ttt gge ate. atg 2377 Lys Tyr Met Thr Val Ser Glu Leu Lys Thr Glu Val Phe Gly Ile Met 735 aac cgg cat ate Asn Axg His Ile 740 gcg gaa gag cag Ala Giu Giu Gin 77 cgt cgc tac Arg Arg Tyr cag gct ttt Gin Ala Phe 750 2425 ggt gaa Gly Giu 765 gtc cgt aac cag Val Arg Asn Gin ggc agt gaa cag Gly Ser Giu Gin caa aaa cag gct Gin Lys Gin Ala 2473 2521 ga a Gi u 780 atg gcg Cta aat Met Ala Leu Asn cag Gin 785 tta att aac cgt Leu Ile Asn Arg tat Tyr 790 cag atg ata cgt Gin Met Ile Arg gca Ala 795 ggc aaa caa Gly Lys Gin tagtggtagc cataatgcag gagcaaagcc tgaatcagga 2570 2624 agagttattc tgactgagtt tggttttctg gcgattcttg ig atg gtg gga tgt Met Val Gly Cys 800 gct tgg tta get gaa cag gec ttt tcc gac cat gcg Ala Trp Leu 805 Ala Giu Gin Ala Ser Asp His Ala ctt Leu 815 tea cca cac Ser Pro His 2672 agi get S er Ala 820 tgg ceg tac agt Trp Pro Tyr Ser tcg cgc gat gee Ser Arg Asp Ala ggg Gi y 830 ctg gec gat aeg Leu Ala Asp Thr ggC Gi y 835 gcg ggc ggc tat Ala Gly Gly Tyr ccc Pro 840 act tgt aaa cag Thr Cys Lys Gin egg tgg A-rg Trp 845 gec gae gac Ala Asp Asp ace Thr 850 2720 2768 2816 gtt ggg ctg aaa Val Gly Leu Lys cgt eta ctg caa Arg Leu Leu Gin cct gee eta gat Pro Ala Leu Asp ate tgg Ile Trp 865 acg geg ttt Thr Ala Phe aaa ate gac cag Lys Ile Asp Gin tcg Ser 875 eag gia gtg tat Gin Val Val Tyr gaa gag gee Giu Giu Al1a 880 tcg cag aat Ser Gin Asn 2864 gtg ctg cgc tcg egg gte Val Leu Arg 885 Ser Arg Vai agt gaa Ser Giu 890 cga aat atg eag Arg Asn Met Gin ggt aac gtt gat Gly Asn Val Asp gta Val 895 2912 ggg cgc gtt tat cca agc tat ggc Gly Arg Val Tyr Pro 5cr Tyr Gly ggc ae gte gee Gly Thr Val Ala 2960 900 gcc gec acc cgg A-1a Ala Thr Arg aat Asn 915 905 ttg gca Leu A-la 920 tee ggc gct Ser Gly Ala aga Arg 925 aat atc ctc ggc agc 3008 Asn Ile Leu Gly Ser 930 iaggcactac cg atg gta 3059 Met Val ata gcg gca igt Ile Ala Ala Cys acg Thr 935 gca tic gac agc Ala Phe Asp Ser gig cgt Val Arg 940 cag gcg Gin Ala 945 cag ctg caa ata Gin Leu Gin Ile gcg Al a 950 ctg gig atc igi Leu Val Ile Cys ccg ctg ata acg Pro Leu Ile Thr cc Leu 960 tgt tcg gcg igg Cys Ser Ala Trp gig aaa gta gig Val Lys Val Val atig Met 970 acg cig acg tt Thr Leu Thr Phe gig Val 975 3107 3155 3203 cag tit gca. cia Gin Phe Ala Leu iii Phe 980 tic cic acc ttt Phe Leu Thr Phe igg Trp 985 tgg gaa cig gca Trp Giu Leu Ala Cgg igg Arg Trp, 990 ctt gat agc Leu Asp Ser agc tgg aat Ser Trp Asn 1010 tgg Trp, 995 ctg cig gat gtg cic Leu Leu Asp Val Leu 1000 tac aac age gat Tyr Asn Ser Asp ace cac agi Thr His Ser 1005 gig ait atc Val Ile le 3251 3299 iia gcc ggg Leu Ala Gly atc cag Ile Gin 1015 aat acg cag gat Asn Thr Gin Asp gac Asp 1 020 aai ctg gig aig agg Asn Leu Val Met Arg 1025 tig atg Leu Met 1030 iii ctg gig tig ccg Phe Leu Val Leu Pro 1035 aca. tic igg cig Thr Phe Trp Leu 3 347 3395 ggg gcg Gly Ala 1040 aig acg igg gci Met Thr Trp Ala 1045 gga. gig agg gii ggc Gly Val Arg Val Gly 1050 gig gcg cig aat gga Val Ala. Leu Asn Gly 1055 gcg cig gcg gga Ala, Leu Ala Gly igattgggag gtgaticgcc aaicicactt icciatacac 3447 atataaaatg ta ai~g aaa tat cic itt ttt gag aat ata cat ici ata itt 3498 Met Lys Tyr Leu Phe Phe Glu Asn Ile His Ser Ile Phe 1060 1065 1070 tia. aca tic agi cic tic cga aca ici, gig icg cci gai tic cca aig 3546 Leu Thr Phe Ser Leu Phe Arg Thr Ser Val Ser Pro Asp Phe Pro Met 1075 1080 1085 -00 ati ttt Ile Phe 1090 tia act Leu Thr 1105 gca tig ccc ica ate att tta ggt caa ttt acg ace aac caa Ala Leu Pro Ser Ile Ile Leu Gly Gin Phe Thr Thr Asn Gin 1095 1100 aac itt gtg ata tgt atg ggt aac ace gtt gaa cgt cgg ctg Asn Phe Val Ile Cys Met Gly Asn Thr Val Giu Arg Arg Leu 1110 1115 1120 ggt gtt gtt cat aat ccc ttt aaa agg tct ggg gat ggc cat gac ctc Gly Val Val His Asn Pro Phe Lys Arg Ser Gly Asp Gly His Asp Leu 1125 1130 1135 agg gcg gta gcg tgaccaaagi tcatatccat accaattatt tiatttaaa Arg Ala Val Ala 1140 atatcaactt attcgagttg tittaittag ticaaagaag gtatcaaa tig ata gt Leu Ile Val 3594 3642 3690 3742 3799 3847 3895 ata gat Ile Asp 1145 get ggc Ala Gly 1160 ttt tit tgt ggc tgt Phe Phe Cys Gly Cys 1150 ggt gga gcc agt gaa Gly Gly Ala Ser Giu 1155 ggg cta cgi cag Gly Leu Arg Gin caa caa gca tca Gin Gin Ala Ser 1175 tit gat atc gag Phe Asp Ile Giu 1165 ctt gga Leu Gly ita gat att Leu Asp Ile 1170 gaa aca iii aaa gct Giu Thr Phe Lys Ala 1180 aat ttc cct Asn Phe Pro gat gca Asp ALla 1185 aaa ttc atc caa gat gat Lys Phe Ile Gin Asp Asp 1190 3943 ati agg Ile Arg aaa atc Lys Ile 1195 gaa cci caa Giu Pro Gin gat atc Asp Ile 1200 tce gac atc att gat Ser Asp Ile Ile Asp 1205 ait aaa Ile Lys 3991 gct aaa cgg Ala Lys Arg 1210 cci tig ita Pro Leu Leu cig agt Leu Ser 1215 gca tgt gca cca tgt Ala Cys Ala Pro Cys 1220 caa cca ttt Gin Pro Phe 4039 tcg caa Ser Gin 1225 cag aat aaa Gin Asn Lys aai aaa Asn Lys 1230 act agt gac gac: ica Thr Ser Asp Asp Ser 1235 agg aga aat cta Arg Arg Asn Leu 4087 cia aat gaa act cat cgt tti ati aga gaa cii ctt cci gaa tat at Leu Asn Giu Tkir His Arg Phe Ile Arg Giu Leu Leu Pro Glu Tyr Ile 4135 1240 1245 1250 1255 atg ctt gaa aat gtt cct Met Leu Glu Asn Val Pro 1260 gga atg caa aaa Gly Met Gin Lys 1265 att gat gaa gaa aaa gaa Ile Asp Giu Giu Lys Giu 1270 4183 ggc cca ttt cag Gly Pro Phe Gin 1275 gag ttt att Glu Phe Ile aag cta Lys Leu 1280 ctt aaa gag tta Leu Lys Glu LeL Lgag tat aac iGlu Tyr Asn 1285 ccc caa aga Pro Gin Arg 4231 4279 tat ata tct Tyr Ile Ser 1290 ttt ata gcc Phe Ile Ala aat gct Asn Ala 1295 gag aac tat Glu Asn Tyr ggg att Gly Ile 1300 aga aaa Arg Lys 1305 cca gag Pro Giu 1320 aga ctc gtg ctc tta A.rg Leu Val Leu Leu 1310 gct agt cga gia ggt Ala Ser Arg Val Gly 1315 aaa gtt ace cta Lys Val Thr Leu 4327 4375 ata acc cat ggt Ile Thr His Gly 1325 aaa aat aaa Lys Asn Lys ate cca Ile Pro 1330 ttc aaa act Phe Lys Thr gta cga Val Arg 1335 gat tat atc Asp Tyr Ile cag gac Gin Asp 1340 ttc aca aag Phe Thr Lys tia tgt Leu Cys 1345 tca gga gaa Ser Gly Giu ace gac ccc Thr Asp Pro 1350 4423 aaa. gat cct tta cat agg gct Lys Asp Pro Leu His Arg Ala 1355 gga aca Gly Thr 1360 ctg agc cct ctt aac Leu Ser Pro Leu Asn 1365 cta aaa Leu Lys 4471 aga att atg Arg Ilie Met 1370 cac act cca His Thr Pro gaa gga Giu Giy 1375 ggg gat aga Gly Asp Arg aga aat tgg cca gaa Arg Asn Trp Pro Glu 1380 4519 gag tta Giu Leu 1385 gtt aat aaa Val Asn Lys tgc cat Cys His 1390 aaa aat tat gat ggc cac aca gat act Lys Asn Tyr Asp Gly His Thr Asp Thr 1395 4567 tat gga aga atg agt tgg gat Tyr Gly Arg Met Ser Trp, Asp 1400 1405 tgt aat agt tac tcc aat ggt Cys Asn Ser Tyr Ser Asn Gly 1420 aag cct gcg cct aca ctt acg Lys Pro Ala Pro Thr Leu Thr 1410 acg aaa Thr Lys 1415 4615 cgt ttt ggg cat cct gac A.rg Phe Gly His Pro Asp 1425 ccc act caa Pro Thr Gin 1430 4663 cat aga gca. att agc ata aga gaa gca tca aga tta caa aca. ttt cct His Arg Ala Ile Ser Ile Arg GlU Al1a 5cr Arg Leu Gin Thr Phe Pro 1435 1440 1445 4711 tta agc tat gtt ttt aaa ggt tcg cig aat tca atg gca aag caa atc Leu Ser Tyr Val. Phe Lys Gly Ser Leu Asn Ser Met Ala Lys Gin Ile 1450 1455 1460 ggc aat gct gta cct tgc gaa ctc gct aga cta ttt ggg cta cat ctc Gly Asn Ala Val. Pro Cys Glu Leu Ala Arg Leu Phe Gly Leu His Leu 1465 1470 1475 475 9 4 8077 ata gaa aat tgt act aat aag gat tca tagatatatg gctaaaataa 4854 Ile Giu Asn Cys Thr Asn Lys Asp Ser 1480 1485 gaacaaaggc tcgagctttg gac atg ctt ggc aga caa caa att gca ggt ata 4907 Met Leu Gly Arg Gin Gin Ile Ala Gly Ile 1490 1495 cct act Pro Thr 1500 gcc ttg agt. gag tta itt aaa aat gct cat gat gcc tat gct Ala Leu Ser Giu Leu Phe Lys Asn Ala His Asp Al1a Tyr Ala 4955 1505 1510 gat aat gic Asp Asn Vai 1515 aga gat gat Arg Asp Asp, ttg act att Leu Thr Ile aaa eca gca Lys Pro Ala 1565 gaa. gtt gat Giu Val Asp 1520 itt ttt agg aaa gaa Phe Phe Arg Lys Glu 1525 aat ctt cit aic ttg Asn Leu Leu Ile Leu 1530 5003 5051 gga tia Gly Leu 1535 gga acc Giy Thr 1550 ggt aig aca ace gat Gly Met Thr Thr Asp 1540 gaa ttt gaa Glu Phe Glu gag agg tgg Giu Arg Trp 1545 icc agc aaa tta Ser Ser Lys Leu 1555 atc gac gat Ile Asp Asp gat gca ait aat Asp Ala Ile Asn 1560 5099 5147 gig gat agt Val Asp Ser aat aaa, Asn Lys 1570 gcc tit cgc Ala Phe Arg cct atc Pro Ile 1575 atg gga gag Met Gly Giu aaa gga Lys Gly 1580 git ctt Val. Leu 1595 ata ggc cgt Ile Gly Arg tta tct Leu Ser 1585 atc gca gca Ile Ala Ala ait gga Ile Giy 1590 cca cag gtg ctg Pro Gin Val Leu act agg gcc aaa Thr Arg Ala Lys 1600 aga gac aat Arg Asp Asn gag ctt Glu Leu 1605 aag cca tia Lys Pro Leu git gct Val Ala 1610 5195 5243 5291 gca iii gt Ala Phe Val aat tgg agt tia Asn Trp, Ser Leu 1615 ttt gct ata cca ica cit gat ctt gat Phe Ala Ile Pro Ser Leu Asp Leu Asp 1620 1625 gat ata gaa ata cca ati aga act att aic aac gac gaa igc ttc act Asp Ile Giu Ile Pro Ile Arg Thr Ile Ile Asn Asp Giu Cys Phe Thz 1630 1635 1640 5339 aaa aaa act ctt Lys Lys Thr Leu 1645 gat gag atg att gag Asp Giu Met Ile Giu 1650 caa gca aga aat aat tia gac 5387 Gin Ala Arg Asn 1655 Asn Leu Asp tct tta Ser Leu 1660 caa tta Gin Leu 167 5 tca cac aaa Ser His Lys ata rca Ile Ser 1665 aaa ica aaa Lys Ser Lys gta tca Vai Ser 16,70 caa ata aat aca Gin Ile Asn Thr tca tct tit gaa Ser Ser Phe Giu 1680 ttt gat cct Phe Asp Pro att cta Ile Leu 1685 tgg gaa aaa aaa tta Trp, Giu Lys Lys Leu 1690 5435 5483 5531 ggt ggg cia aga cia Gly Giy Leu Arg Leu 1695 tct gga gat Ser Giy Asp ggg cat Giy His 1'700 gga act cac tic ata ata Giy Thr His Phe Ile Ile 1705 aig cct acc gaa Met Pro Thr Giu 1710 gaa ata tta Giu Ile Leu ata gat Ile Asp 1715 gac att icc acg ALsp Ile 5cr Thz agc gat agc Ser Asp 1720 tta tta ggt Leu Leu Giy aai aaa aca Asn Lys Thr 1725 ttt aca aac Phe Thr Asn 1740 ica gag cag Ser Giu Gin tct t Ser Ser 1730 cgc tta gaa Arg Leu Giu aaa gct Lys Ala 1735 55*79 5627 5675 aca aig tac agi Thr Met Tyr Ser 1745 gat tca aac Asp Ser Asn cct cci Pro Pro 1750 ait ata gct cgt Ile Ile Ala Arg iii aga Phe Arg 1755 gac tat cig gaa Asp Tyr Leu Giu 1760 gai ggt gag igc ati Asp Giy Giu Cys Ile 1765 gic aga ait agc gaa Asp Arg Ile Ser Giu 1770 5723 5771 ica. att tt Ser Ile Phe iii aca Phe Thr 1775 ccg caa gaa ttc aat Pro Gin Giu Phe Asn 1780 cit gca gat cac cac ati Leu Ala Asp His His Ile 1785 gaa. gga Giu Giy tgg tic aat Trp Phe Asn 1790* gaa tit ggt caa Giu Phe Giy Gin .1795 tic agi gga act Phe Ser Gly Thx *git tci gtt *Vai Scr Vai 1800 5819 tat ggt gaa gag cca ati cat cat gtc gtg act Tyr Gly Giu Giu Pro Ile His His Val Val Thr t gg Trp aaa aat aat aai Lys Asn Asn Asn 5867 1805 1810 1815 caa tta Gin Leu 1820 ggt Cgg Gly Arg 1835 acc caa tgc ggt Thr Gin Cys Gly cit cgt gat ica Leu Arg Asp Ser 1840 ttt aaa ata aaa tia Phe Lys Ile Lys Leu 1830 gcg tat att cat Ala Tyr Ile His cgc tta ccc aig gag A.rg Leu Pro Met Glu 1845 tig tgg Leu Trp gec cct ctg Ala Pro Leu 1850 5915 5963 6011 6059 aag gag aaa Lys Giu Lys aca gat Thr Asp 1855 aga tat ggt Arg Tyr Gly ggt tia Gly Leu 1860 tat atc tat cga Tyr Ile Tyr Azg gat gga Asp Gly 1865 aaa ata Lys Ile tta aga att ttg Leu Arg Ile Leu 1870 ccc tat gga Pro Tyr Gly gat tca Asp Ser 1875 gat acg gat A-sp Thr Asp itt cia Phe Leu 1880 gaa aag aga Giu Lys Arg 1885 aga acg tta tcc gct Axg Thr Leu Ser Ala 1890 ici gaa tat tit tic Ser Giu Tyr Phe Phe 1895 tca tat cga Ser Tyr Arg 6107 cgt tig Arg Leu 1900 git gaa Val GiU 1915 ttt gga gca Phe Gly Ala ata gaa Ile Glu 1905 ita aca aaa gaa aac Leu Thr Lys Giu Asn 1910 aai gct ica tia Asn Ala Ser Leu 6155 aaa gct Lys Ala ggg cga Gly Arg 1920 gaa gga tic ait gaa Giu Gly Phe Ile Giu 1925 aai aag cca tat aaa Asn Lys Pro Tyr Lys 1930 6203 cag iii aaa Gin Phe Lys gaa atg GiU met 1935 cit gaa aat Leu Glu Asn tic ttc Phe Phe 1940 atc gaa aic Ile Giu Ile tic tti aag gac Phe Phe Lys Asp 1950 caa cgi aga aat Gin Arg Arg Asn 1965 gat ggc gat Asp Gly Asp gaa gaa cat Giu Giu His aig t Met Ser 1955 gaa tia tdi gt Giu Leu Phe Val gca aga gat Ala Arg Asp 1945 gag aca aag Glu Thr Lys 1960 ici aaa caa Ser Lys Gin 6251 6299 6347 gat Asp L970 tig ita ici aaa aga Leu Leu Ser Lys Arg 1975 act aaa Thr Lys 1980 gct aaa aaa Ala Lys Lys gat aga Asp Arg 1985 ita aag aaa gat ctg Leu Lys Lys Asp Leu 1990 tat gai itt tii Tyr Asp Phe Phe 6395 6443 gat aag ita gat aat Asp Lys Leu Asp Asn 1995 2 gat tac igg aai Asp Tyr Trp Asn 000 ati gaa ata aat aag cta aic Ile Giu Ile Asn Lys Leu Ile 2005 2010 :71 00 aai aaa aac gag gaa Azn Lys Asn Giu Giu 2015 ata gat tat gia tac Ile Asp Tyr Val Tyr 2030 tat tic tee agt aca Tyr Phe Ser Ser Thr 2020 aat aaa att aaa gaa Asn Lys Ile Lys Giu 2035 gaa ata aca gac acc aat Giu Ile Thr Asp Thr Asn 2025 caa aat gat gct atc at Gin Asn Asp Ala Ile Ile 2040 6491 6539 aaa aat cia cgt Lys Asn Leu Arg 2045 aat ict gtg gat Asn Ser Val Asp 2050 ata aag aaa Ile Lys Lys ccc tct Pro Ser 2055 gga git gga Giy Val Gly 6587 tia aca Leu Thr 2060 caa aaa Gin Lys 2075 aaa gag tta Lys Giu Leu tct aat Ser Asn 2065 tta igg gat Leu Trp Asp aga tat Arg Tyr 2070 caa ata gaa aga Gin Ile Giu Arg 6635 6683 ata ctg tia tca Ile Leu Leu Scr 2080 cia aat gag Leu Asn Glu cta aaa. Leu Lys 2085 gat aac gtt gat aga Asp Asn Val Asp Arg 2090 aag cit ata Lys Leu Ile gaa ctg Giu Leu 2095 gat aat aaa Asp Asn Lys aat aat Asa Asn 2100 gat ttt cic Asp Phe Leu aag aga ctt gaa Lys Axrg Leu Glu 2120 gaa cia aca aag Giu Leu Thr Lys 2125 gat ici tig aat cia, Asp Ser Leu Asn Leu 2115 caa caa agi tac Gin Gin Ser Tyr aaa. aai gct tig Lys Asn Ala Leu 2135 aac ita. cgg Asn Leu Arg 2105 tat gaa aaa Tyr Giu Lys Z 120 aaa gai gig Lys Asp Val 6731 6779 6827 ita tat aat gac Leu Tyr Asn Asp 2130 gct Al a caa tci Gin Ser 2140 aaa gca aat Lys ALla Asn agg ita Arg Leu 2145 att. ici gat Ile Ser Asp aai ahg Asn Lys 2150 aaa aaa cat aag Lys Lys His Lys 6875 agi gaa cia aaa aac ait ici tat gaa Ser Giu Leu Lys Asn Ile Ser Tyr Giu tic caa. Phe Gln 2165 ica aci aat cic aat Ser Thr Asn Leu Asn 2170 6923 2155 2160 ggc aaa gat Gly Lys Asp act gcg Thr Ala 2175 tat aia tig Tyr Ile Leu gat gia. Asp Val 12180 aaa. aga aat Lys Arg Asn cia gaa agi Leu Giu 2185 6971 aaa ait gag aat act tca aac gaa gig atti aat gaa ata aga aaa cia Lys Ile Glu Azn Thr Scr Asn Glu Val Ile Asn Glu Ile Arg Lys Leu 2190 2195 2200 7019 ace gac cag Thr Asp Gin 2205 ait gca ata atti agt Ile Ala Ile Ile Ser 2210 gat agt ace act Asp Ser Thr Thr 2 tot gaa aat tia Ser Giu Asn Leu 215 ctt gaa cat tta Leu Giu His Leu ica tcg Ser 5cr 2220 cga gac Arg Asp 2235 gct caa gia Ala Gin Val act gaa Thr Giu 2225 gca atc gaa Al1a Ile Giu act gaa Thr Giu 2230 '7067 7115 7163 oaa caa gca aat GIn Gin Ala Asn 2240 aac gca gag Asn Ala Giu tta ata Leu Ile 2245 ota cti ggc Leu Leu Gly atg got Met Ala 2250 cii tot. gta Leu Ser Val gta cat Val His 2255 cat gaa ttt His Giu Phe aat ggt Asn Gly 2260 aat att. agg Asn Ile Arg goa att aga Ala Ile Arg 2265 7211 agt gcg cta agg Ser Ala Leu Axg 2270 gaa ita aaa Giu Leu Lys gca tgg Ala Trp 2275 gct gac aga aat oct Ala Asp Axg Asn Pro 2280 aag ct Lys Leu 7259 gat att ata Asp Ile Ile 2265 tao caa aaa atc aga Tyr Gin Lys Ile Arg 2290 act agt tti gat cac Thr Ser Phe Asp His 2295 tta gat ggt Leu Asp Gly 7307 tat ita Tyr Leu 2300 acc aat Thr Asn 2315 gat gat Asp Asp aaa ace iii Lys Thr Phe ata act gga Ile Thr Gly cgt ctt gag Arg Leu Giu 2335 aca oca Thr Pro 2305 ttg aca aga cgt tia Leu Thr Arg Arg Leu 2310 agt cgc tct aaa Ser ALrg Ser Lys -act Thr 2 320 gco att tta gaa tti Ala Ile Leu Giu Phe 2325 atc aga gat Ile Arg As; gta to Val Phe 2330 tca aag Ser Lys 2345 7355 7403 7451 aaa gaa gga ati gaa Lys Giu Gly Ile Glu 2340 ita ttc act ace Leu Phe Thr Thi iii git aat caa Phe Val Asn Gin 2350 gaa att gia Giu Ile Val act tac Thr Tyr 2355 aca tca ace Thr Ser Thr ait tao cci, gic Ile Tyr Pro Val 2360 7499 itt ata aai cta ati gat aac gca ata Phe Ile Asn Lau Ile Asp Amn Al1a Ile 2365 2370 tac tgg ctt ggg Tyr Trp, Leu Gly 2375 aaa aca act Lys Thr Thr 7547 gga gaa aaa. aga cit ata ctti gat got act gaa. aca gga itt git at Gly Glu Lys Axrg Lau Ile Lau Amp Ala Thr Glu Thr Giy Phe Val Ile 7595 2380 2385 2390 ggt gat act ggt ccc ggt gtt tca act aga, gat cga gat ata aia ttt Gly Asp Thr Gly Pro Gly Val Ser Thz Arg Asp Arg Asp Ile Ile Phe 2395 2400 2405 2410 7643 gat atg gga ttt aca Asp Met Gly Phe Thr 2415 att tcc aaa gag tgt Ile Ser Lys Glu Cys 2430 gat tac act cct gaa Asp Tyr Thr Pro Giu 2445 gaa aca agt gaa tag Giu Thr Ser Giu 2460 cat aaa ctt tct gaa His Lys Leu Ser Giu 2475 gct gta gat gac aat Ala Val Asp Asp A-sn 2490 cga aaa aca gga ggg cgt gga atg gga tta. ttc A.rg Lys Thr Gly Gly Arg Gly Met Gly Leu Phe 2420 2425 tta tct cga gat gga ttt act ata aga. ttg gat Leu Ser Axg Asp Gly Phe Thr Ile Arg Leu Asp 2435 2440 cag ggt gct.ttc ttt att att gag cca, tca gaa, Gin Gly Ala Phe Phe Ile Ile Giu Pro Ser Glu 2450 2455 cggatataaa taa atg aca agc tct act gat ttt Met Thr Ser Ser Thr Asp Phe 2465 2470

7691. 7739 7787 7836 gac tgc gtt cgc cgjt Asp Cys Val Arg Arg 2480 atg tct ttt gga gct Met Ser Phe Gly Al1a 2495 ttt tta cat tct gta gtt Phe Leu His Ser Vali Val 2485 ggt agt. gat act ttc cct Gly Ser Asp Thr Phe Pro 2500 7884 7932 aca gac gaa Thr Asp Giu 2505 gat att. Asp Ile aat gct tta Asn Ala Leu 2510 gtt gat ccc gac gat Val Asp Pro Asp Asp 2515 gat cct aca. Asp Pro Thr '7980 cca ata Pro Ile 2520 aaa. gca Lys Ala 2535 ata aca gca tca gca Ile Thr Ala Ser Ala 2525 tcc cca agg Ser Pro Arg ata gaa Ile Giu 2530 tca act aaa tca Ser Thr Lys Ser 8028 8076 aag gta aaa aac Lys Val Lys Asn 2540 cat cct ttt His Pro Phe gat tac Asp Tyr 2545 caa gct cta gca gaa Gin Ala Leu Ala Glu 2550 gct ttc gcc Ala Phe Al-a aaa gat Lys Asp 2555 ggt att gct Gly Ile Ala tgt tgc Cys Cys .2560 gga tta tta Giy Leu Leu gct aag agt Ala Lys Ser 2565 8124 ttt aat gtt gaa gaa aga gat ata att aca gca tca tcc cac aag gca Phe Asn Val Giu Giu ALrg Asp Ile Ile Thr Al1a Ser Ser His Lys Ala 8172 2570 2575 2580 gat ata aca Asp Ile Thr 2585 ata ctt gac tgg gat Ile Leu Asp Trp Asp 2590 atg caa agc gat agt Met Gin Ser Asp Ser 2595 ggg caa ttt Giy Gin Phe 8220 gct at Ala Ile 2600 gga cgt Giy Arg 2615 gaa ata. ata Gu Ile Ile aaa tcg Lys Ser 2605 ata atc gt Ile Ile Val ica gat Ser Asp 2610 ata aai tot gga Ile Asn Ser Gly 8268 8316 tta, cgt cit ctt Leu Arg Leu Leu 2620 tot ait tat Ser Ile Tyr act ggt Thr Gly 2625 gaa. cat gtt Giu His Val act got Thr Ala 2630 gtt ata act Val Ile Thr aag ttg Lys Leu 2635 aac aat gag Asn Asn Giu tta. aag Leu Lys 2640 aaa aca tao Lys Thr Tyr ogt ago gta Arg Ser Val 2645 ata aaa, aat gat Ile Lys Asn Asp 2650 gat agt att Asp Ser Ile ttt att. Phe Ile 2655 gaa gat aac Giu Asp Asn tat gca cto gaa Tyr Ala Leu Giu 2660 8364 8412 8460 oaa. tgg tgrt Gin Trp, Cys 2665 ata. gtt gtt Ile Val Val att agt Ile Ser 2670 aaa gao gtt Lys Asp Val tat gaa Tyr Glu 2675 aaa. gat ott Lys Asp Leu oca aat Pro Asn 2690 too aac Ser Asn 2695 gtg tta, ata. Val Leu Ile goc gca oto Al1a Ala Leu aaa aaa Lys Lys 2685 ttc act aao ott aca Phe Thr Asn Leu Thr 2690 got ggg ttg ota Ala Gly Leu Leu tct tgo att tot Ser Cys Ile Ser ~700 tat aat aat aaa Tyr Asn Asn Lys gaa ata, Glu Ile 2705 aga. gaa aaa aco oat Arg Glu Lys Thr His 2710 8508 8556 8604 ggg ata tta Giy Ile Leu aca aaa, Thr Lys 2715 tta Leu ~72 0 gao act gca tat gtt too Asp Thr Ala Tyr Val Ser 2725 cac ato tta, aat His Ile Leu Asri 2730 tta ata aaa too aag gag toa agg Leu Ile Lys Ser Lys Glu Ser Arg 2735 goa tat got tat Ala Tyr Ala, Tyr 2740 8652 gaa, aat got Giu Asn Ala 2745 oat gat tat His Asp Tyr gca gta, Ala Val 2750 gat Asp tta att tot gaa Leu Ile Ser Glu 2755 gaa ata aga Glu Ile Arg 8700 toa. ata ttg oaa, ata agt gaa. aao tta aag aaa, tot ota ago aaa aao Ser Ile Leu Gin Ile Ser Giu Asri Leu Lys Lys Ser Leu Ser Lys Asn 8748 2760 2765 2770 tce tta Ser Leu 2775 tcc cat tgg Ser His Trp 2 cct att ttt cac tat gca Pro Ile Phe His Tyr Ala 780 278 5 gga, aaa aaa caa aaa gac Gly Lys Lys Gin Lys Asp 2800 aaa aat ggt tgt aag Lys Asn Gly Cys Lys 2790 tta tca gta gaa eat Leu Ser Val Giu His 2805 8796 8844 aat itt cta tta act Asn Phe Leu Leu Thr 2795 cia. agg aat ata Leu Arg Asn Ile 2810 etc tct gct Leu Ser Ala gat tet Asp Ser 2815 ita gaa gaa Leu Glu Giu att caa cac gct Ile Gin His Ala 2820 8892 8940 ait gaa, cac Ile Giu His 2825 gca ict tia Ala Ser Leu ggt aaa Gly Lys 2830 aag gaa tac Lys Glu Tyr tia agc Leu Ser 2835 caa gat ggt Gin Asp Giy gaa. gaa. Giu Giu 2840 agg agt Arg Ser 2855 gat aaa aag tta. atg Asp Lys Lys Leu Met 2845 caa ita tge tct ctg Gin Leu Cys Ser Leu 2850 gaa ate acg cgc Giu Ile Thr Arg 8988 tta aga Leu Arg tat eat Tyr His 2860 tet cat ata Ser His Ile gat aat Asp Asn 2865 gtg tcc ita aaa caa Val Ser Leu Lys Gin 2870 9036 gga act tta Gly Thr Leu ctt tta Leu Leu 2 8'75 gat gea. tat Asp Ala Tyr aat ttt Asn Phe 2880 gte tat cia igc ata, caa Vai Tyr Leu Cys Ile Gin 2885 9084 eca ita tgt gat Pro Leu Cys Asp 2890 agc gte aga. ttg cat Ser Vai Arg Leu His 2895 gaa aaa gcc Glu Lys Ala gat ttt ita ttc Asp Phe Leu Phe 2900 9132 9180 etc agg gga Leu Arg Gly 2905 aca ctg gac Thr Leu Asp gat aat Asp Asn 2910 aat tac aat ttg tta Asn Tyr Asn Leu Leu 2915 ate gaa gat Ile Giu Asp gaa tat Giu Tyr 2920 ati ati Ile Ile 2935 ggc ggt ttt Gly Gly Phe tat aaa Tyr Lys 2925 ait aaa atg Ile Lys Met ccg gca Pro Ala 2930 aaa gct tct aat Lys Ala Ser Asn 9228 9276 tea tit tea tt Ser Phe Ser Phe 2940 gga. gte gaa aat gga, Giy Val Giu Asn Gly 2945 aac ggt gte atc ata. Asn Gly Val Ile Ile 2950 ggg aaa aag aac aat cia. git aat Gly Lys Lys Asn Asn Leu Val Asn 2955 act gac tat atc tea tic. gtt cci Thr Asp Tyr Ile Ser Phe Vai Pro 9324 2960 2965 tta ctc gtt gaa aaa ata tct act cca aaa gta ttg aaa tgg atc ggg Leu Leu Val Glu Lys Ile Ser Thr Pro Lys Val. Leu Lys Trp Ile Gly 2970 2975 2980 9372 9420 gaa ata aaa Glu Ile Lys 2985 aat cig tca Asn Leu Ser 3000 aca acg tac Thr Thr Tyr gcg caa aaa Ala Gin Lys 2990 ata aca act gat Ile Thr Thr Asp 2995 att gtt gct Ile Val. Ala aga ata ggt tia gat Arg Ile Gly Leu Asp 3005 caa cat gag tgg tia Gin His Giu Trp Leu 3010 cga ata aaa Arg Ile Lys 9468 tca aaa gat ata iaaatgatta tatatgccgt cgttttataa aaactggcgg 9520 Ser Lys Asp Ile 3015 catgtatatc tagitagiec atcatagaag tcaagaaatt tagttigccc tatatcttat 9580 agaaaatata. ttttatatgc ttaaaaaaca ccatctttct aagatggcat ttaigigctt 9640 tgtttcgatc aattacaact gatatattac catattgatt aattttatgt tatttaccaa 9700 agtaacggca tcttaatata tcgtcaiaat atagtgcgcg ttctgactet aatactgaaa 9760 aatttatttg tetattita cacttactgc aaatagcatc cagtttatca iatagtgtcg 9820 catcaattgg cgcag atg tca ica cgc caa atc ctt gag cat tat aat gct Met Ser Ser Arg Gin Ile Leu Giu His Tyr Asri Ala 9871 3020 3025 3030 cia aca tat ccc cta Leu Thr Tyr Pro Leu 3035 aat ttg tia tea gtt Asn Leu Leu Ser Val. 3050 cat caa tca atc ttg HiLs Gin Ser Ile Leu 3040 tgc act gga aaa tee Cys Thr Gly Lys Ser 3055 ttg cag ata atg act tcg Leu Gin Ile Met Thr Ser 3045 9919 9967 att tac Ile Tyr gag gat ate tcc Giu Asp Ile Ser 3060 ggc agt tct Gly Ser Ser 3065 aga gcg aga Arg Ala Arg 3080 tgg aat atc ata cac Trp Asn Ile Ile His 3070 ctt'icc ata ttt tct Leu Ser Ile Phe 5cr 3085 tic aat ate Phe Asn Ile cct ctc Pro Leu 3075 ccc atc tct Pro Ile Ser aaa cot tgg Lys Pro Trp 10015 10063 tat tgt gtc aga att Tyr Cys Val Arg Ile 3090 atg agt atg gat tao aig taaccggctc atttaaaccg tctggtctgt Met Ser Met Asp Tyr Met 10111 3095 3100 ttcctccggt tacaaaaa ta aig icc atc ati itt aat gga cac tat cgt Met Ser Ile Ile Phe Asn Gly His Tyr Axg 3105 3110 10163 atg aaa cac egg act tgg Met Lys His Axg Thr Trp, 3115 atc act gaa get ita cgt cit cac ttt gaa Ile Thr Glu Ala Leu Arg Leo His Phe Glu 3120 3125 10211 gaa cat tia ccc cag Giu His Leu Pro Gin 3130 git gig gte ggg Val Val Val Gly 3135 cgt cgc ctg ggc gia A-rg Arg Leu Gly Val 3140 cca aaa Pro Lys 10259 10307 ica aca gct Ser Thr Ala 3145 igi ggt aig Cys Gly Met tic gig Phe Val 3150 cgc tit cgc aaa get ggc iii ica Arg Phe Arg Lys Ala Gly Phe Ser 3155 tgg cci ctg ccc gca ggi aig icg Trp Pro Leu Pro Ala Gly Met Ser 3160 3165 gag cgg gag cit gat Giu Arg Glu Leu Asp 3170 ggc egi ct Gly Arg Leo 10355 10403 tac ggg Tyr Gly 3175 agi acc icc aca gta cct gic Ser Thr Ser Thr Val Pro Val 3180 gia cii igi Val Leu Cys 3185 agi gga tcg gia Ser Gly Ser Val 3190 att, cag gac Ile Gin Asp acc tcg aaa icc igt Thr Ser Lys Ser Cys 3195 iaaigitaaa acagtgaaaa igaggigatg 10457 c atg atc aaa act egi cgg act aaa egi acc iii icc ccg gag tic aag Met Ile Lys Thz Arg Arg Thr Lys Arg Thr Phe Ser Pro Glu Phe Lys 10506 3200 3205 1210 cii, gaa Leu Giu 3215 gct tic gag cag Ala Phe Glu Gin 3220 gig gig git aaa tac cag Val Val Val Lys Tyr Gin 3225 cgt gat gic aga Arg Asp Val Arg 3230 10554 gaa gic gcg Giu Val Ala cag gca etc Gin Ala Leu 3235 gag etc aac cci Glu Leu Asn Pro 3240 gac cat tig Asp His Leu cgi aaa igg Arg Lys Trp 3245 10602 aia. cgg Ile Arg tig tat aag Leu Tyr Lys 3250 cag gaa cit cag ggt Gin Glu Leu Gin Gly 3255 ati gag Ile Glu cca gci. ggt aat Pro Ala Gly Asn 3260 10650 gci ait acc cci. gaa caa cgc gaa ait cag cag cit aaa gcg cag ata Ala .Ile Thr Pro Giu Gin Arg Glu Ile Gin Gin Leu Lys Ala Gin Ile 10698 3265 aag cgc gtt Lys Arg Val 3280 atg agc gaa Met Ser Giiu 3295 aagtggccag caggtgaagc catgctctca iggcgttgat tcgacagccg tttactgaac ttttattcg 3270 *gag atg gaa aaa gaa *G1u Met Giu Lys Giu 3285 atc ccc ggg aag ctg Ile Pro Gly Lys Leu 3300 gtcctgttaa tgigcaaag gtcgtggcgc agccgggta( gcaggccggt ggctggcat gttaaacatc acaaccgggl cggcaatttc accccgccg 3275 ata cta aag cag gct gcc gtg ctg 10746 Ile Leu Lys Gin Al1a A-la Val Leu 3290 tcg cgc taatcacaca gctgaaagca 10796 Ser Arg a a* 9 9 t, c ttcggtatta attgaattac ccgggcaatc acgactgatg aaacgaagac accaaactgc accgtagcgt gaagccgggt agtcagatgt cgggaatgag aaaagtccgc gtctggtgcg ttattacgcg gagggctttc igcgccagag ggctgacaag cattgccaaa gcgacatcag 10856 10916 10976 11036 11096 11156 11165 <210> <211> 366 <212> PRT <213> Escherichia coli <400> Ser A-sp Met Gin Arg GI 1 5 Leu Val Gly Gly Asn Me y Ile Gin Ala Al1a 10 Leu Thr Al1a Al a GIly Ala Leu Gin Gly t Ala Giy Asn Ala 25 H is Giu Leu Ala Ala Ala Lys Leu Gin Gly Glu Val Ile Ile Ile Gly Ala Giy Ile Al1 a Asp Val 5cr Ala Pro Asp Asn Thr Thr Ala Ala Ala Ile Ala Asn Ser Ala 70 Ala Ser Ala His Ala Ile Leu Gly Ala Gly Ala Ile Leu Ala Gly Thr Ile Ala Lys Ser Tyr Pro Gly Pro Ser Lys Leu Thr Giu Asp Gin Gln Thr Val Ser Thr Leu Ala Thr Leu Ser Ala Giy Met Ala 115 Giy 120 Gly Ile Ala Ser Giy 125 Asp Val Ala Gly Ala 130 Ala Ala Gy Ala GI y 135 Ala Giy Lys Asn Vai Vai Glu Asn Asn 140 Ala 145 Leu Ser Leu Vai Arg Gly Cys Ala Val 155 Ala Ala Pro Cys Arg 160 Thr Lys Val Ala Glu 165 Gin Leu Leu Glu Gly Ala Lys Ala Gly Met 175 Ala Giy Leu Ser Asp Glu 195 Gly Ala Ala Val Lys 185 Asp Met Ala Asp Arg Met Thr 190 Gly Asn Asp Leu Glu His Leu Thr Leu Gin Met Glu Ile 210 Thr Thr Lys Tyr Leu 215 Ser Ser Leu His Lys Tyr Gly Ser Giy 225 Lys Ala Ala Ser Asn Val Glu Leu Giy 245 Asn Ile Giy Lys Asp 235 Leu Thr Asp Ala Glu 240 Gly Ser Gly Ser Gly 250 Thr Gly Thr Pro Pro Pro 255 Ser Giu Asn Asn Gin Lys 275 Asp 260 Pro Lys Gin Gln Asn 265 Glu Lys Thr Vai Asp Lys Leu 270 Thr Ile Lys Gin Giu Ser Ala Lys Lys Ile Asp Asn Ala 290 Leu Lys Asp His Asp 295 le Ile Gly Thr Lys Asp Met Asp Gly 305 Glu Lys Pro Val Pro Met Gin Asn Thr 325 Glu Asn Gly Gly Tyr 315 Trp Asp His Met Gin 320 Leu Arg Giy Leu Asn His Ala Asp Thr Leu 335 Lys Asn Val Asn 340 Asn Pro Giu Ala Gin 345 Ala Ala Tyr Gly Arg Ala Thr 350 Asp Ala Ile Asn Lys Ile Glu Ser Ala Leu Lys Gly Tyr Gly 355 360 365 <210> 36 <211> 128 <212> PRT <213> Escherichia coli <400> 36 Met Ile Thr Leu Arg 1 5 Lys Leu Ile Gly Ile Asn Met Thr Lys Giu Pro Giu Gin Val Pro Leu Ser Pro Leu Glu Leu Trp Phe Giu Arg Ile Ile Asp Ala Ile Arg Giu Lys Leu Thr Val 40 Giu Asp Leu Cys Axg Gin Asn s0 Leu cys Ile Asp Leu Met Pro Arg Leu Glu Val Leu Thr Lys Giu Pro Leu Ala Leu Ser Thr Ile Ala 70 Gly Giu Tyr Tyr Asp 75 Giy Giu Leu Ile Al a Lys Gly Giu Asp Leu 90 Lys Asp Gin Lys Ser Thr Phe Thr Gin Asn Asp Asp 115 Arg Gin*Leu Ile As n 105 Gin Leu Giu Pro Ser Asp Ile 110 Ile Ile Vai Leu Arg Lys Asp Ile 120 Leu Lys Ile Asn Gln 125 <210> 37 <211> 107 <212> PRT <213> Escherichia ci <400> 37 Met Vai Ala Lys Ala Phe Ala Tyr Ala Leu Asn Gin Trp Pro Ala Leu 1 5 10 Thr Tyr Tyr Ala Asn Asp Giy Trp Val Giu Ile Asp Asn Asn Ile Ala 25 Glu Asn Ala 1.eu Arg Ala Val Ser Leu Gay Arg Lys Asn Phe Leu Phe Phe Gly Ser Asp His Gly Gly Glu Arg Gly Ala Leu Tyr Ser Leu Ile Gly Thr Cys Lys His Val Leu Ala Val Leu 70 Asn Asp Val Asp Pro Glu Ser Tyr Leu 75 Arg Ile Ala Asp Trp Val Asn Arg Val Ser Giu Leu Leu Pro Trp 100 Arg Ile Ala Leu Pro Ala Giu 105 <210> 38 <211> 86 <212> PRT <213> Escherichia cli <400> 38 Met Leu Met I Ser Giu Thr Ile Asn Leu Ser Val Gin Lys Giu Lys 5 Val Ala Giu Ser Val Val Thr Giy Asp Ser Val Tyr Ala Ser Leu Phe Glu Lys Asn Pro Val Ser Ala 40 Leu Ser Ala Leu Asp Asn Pro Phe .Arg Ser Ala Asp Asn Ala. Gly Arg Ile Thr Ser Ile Gln Pro Al1a Val Gin Cys Ala Al a '70 Ala Ala Ala Thr Glu Gly Ser Cys Pro Gin Ser Pro Cys Se: Gly <210> 39 <211> 111 <212> PRT <213> Escherichia ccli <400> 39 Met Val Asp Asn Trp Gin Lys Se: Val Arg Ser Axg Ala Leu Pro Glu 1 Glu Ala Met Ala Giu Arg Thr Gly Trp, Asn Giu Gl.y 25 Met Ile Arg Leu Gln Gin Leu Tyr Met Thr Leu Asn Arg Gin Giu Gin Arg Gly Val Ser Giu Leu Lys Thr Ile Pro Ala Giu 70 Vai Phe Gly Ile Met Gin Ala Phe Asn Tyr Giy Glu Val Arg Axrg His Giu Gin Leu Arg Arg Asn Gin Asn Giy Ser Giu Gin Gin Gin Gin Ala Giu Met Ala Leu Asn Gin Leu Ile 100 Asn ALrg Tyr Gin Met 105 Ile Arg Al1a Giy Lys Gin 110 <210> (211> 143 <212> PRT (213> Escherichia cli <400> Met Vai Giy Cys Ala Trp Leu Ala Giu Gin Ala Phe Ser Asp His Ala Leu Ser Pro Leu Ala Asp Ser Ala Trp Pro Tyr Ser Ala Ser Arg Asp Ala Giy Gin Arg Trp Thr Gly Ala Gly Giy 40 Tyr Pro Thr Cys Lys Ala Asp s0 Asp Thr Vai Gly Lys Ala Arg Leu Leu Gin Leu Pro Ala Leu Tyr Asp Ile Trp Thr Giu Giu Ala Val Phe Lys Lys Ile Gin Ser Gin Val Val Leu Arg Ser Arg Vai 90 Ser Giu Arg Asn Met Gin Vai Ser Gin Asn 100 Giy Arg Val Tyr Pro 105 Ser Tyr Giy Gly Asn Val Asp 110 Gly Thr Val Ala Asn Ala Ala Thr Arg Leu Ala Ser Gly Ala Arg Asn 125 Ile Leu Gly Ser Ile Ala Ala 130 135 Cys Thr Ala Phe Asp Ser Val Arg 140 <210> 41 <211> 118 <212> PRT <213> Escherichia coli <400> 41 Met Val Gin Ala Gin Leu GIn Ile Ala 1 5 Val Ile Cys Ile Pro Leu Ile Thr Leu Phe Vai Gin Ser Ala Trp Asp Lys Val Val Met Thr Leu Thr Giu Leu Ala Phe Ala Leu Phe Phe Leu Thr Phe Trp Arg Trp Leu Asp Ser Trp Leu Asp Val Leu Asn Ser Asp Thr His Ser Ser Trp Asn Leu 70 Ala Giy Ile Gin Asn Thr Gin Asp Asp Ile Ile Asn Leu Met Arg Leu Met Phe s0 Leu Val Leu Pro Thr Phe Trp Leu Gly Asn Gly Ala 115 Ala 100 Met Thr Trp Al1a Gl y 105 Val Arg Val Gly Vai Ala Leu 110 Leu Ala Giy <210> 42 <211> 81 <212> PRT <213> Escherichia coli <400> 42 Met Lys Tyr Leu Phe Phe Giu Asn Ile His Ser Ile Phe Leu Thr Phe Ser Leu Phe A-rg 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 Ilie Cys Met Gly Asn Thr Val Giu Arg Arg Leu Gly Vai Val 55 His Asn Pro Phe Lys Arg Ser Giy Asp Giy His Asp Leu Arg Ala Val 170 75 Al.a <210> 43 <211> 348 <212> PRT <213> Escherichia ci <400> 43 Leu 1 Leu Gln Ile Vai Ile ALrg Gin Ala Ala Ser Giu Asp Giy Phe Phe Cys Giy Cys Gly Giy Ala Ser Giu Gly Leu Phe Asp Ile Giu 25 Asn Giy Leu Asp Thr Phe Lys Phe Pro Asp Ile Asp Gin Lys Phe Ile Asp Ile Ile Gin Asp Asp Ile Arg Lys AsD Ile Ile Pro Pro Gin Asp Lys Ala Lys Leu Leu Leu Gln S er 75 Thr Cys Ala Pro Cys Pro Phe Ser Asn Lys Asn Lys Phe Ser Asp Asp Ser Arg Arg Asn Leu Giu Tyr Ile 115 Glu Lvs Giu Leu 100 Met Giu Thr His Arg 105 Pro Ile Arg Giu Leu Glu Asn Vai 120 Giu Gly Met Gin Leu Leu Pro 110 Ile Asp Glu Lys Giu Leu Gly Pro Phe 130 Giu'Tyr Asn Tyr Ile Ser Gin 135 Phe Phe Ile Lys Leu 140 Ile Ala Asn Ala Giu Asn Tyr Giy Ile Be 160 Gly Lys 115 Pro Gin Arg Arg Arg Leu Val Leu Leu 170 Al~a Ser Arg Val Val. Thr Leu Thr Val. Arg 195 Giu Ile Thr His Lys Asn Lys Ile Pro Phe Lys 190 Ser Giy Giu Asp Tyr Ile Gin As p 200 Phe Thr Lys Leu Cys 205 Thr Asp 210 Pro Lys Asp Pro Leu 215 His Arg Ala Gly Thr Leu Ser Pro 220 Gly Asp Arg Arg Leu Leu Lys ALrg Ile Met 23C His Thr Pro Giu Asn 240 Trp Pro Glu Giu Val Asn Lys Cys His 250 Lys Asn Tyr Asp Gly His 255 Thr Asp Thr Thr Thr Lys 275 Giy Arg Met Ser Asp Lys Pro Ala Pro Thr Leu 270 His Pro Asp Cys Asn Ser Tyr Ser 280 Asn Gly Arg Phe Gly 285 Pro Thr 290 Gin His Arg Ala le A.95t Ser Ile Arg Giu Ala 300 Se: Arg Leu Gin Phe Pro Leu Ser Tyr 310 Val Phe Lys Gly Ser 315 Leu Asn Ser Met Lys Gin Ile Gly Ala Val Pro Cys Gi u 330 Leu Ala Arg Leu Phe Giy 335 Leu His Leu Ile 340 Glu Asn Cys Thr Lys Asp Ser <210> 44 <211> 974 <212> PRT <213> Escherichia coli <400> 44 Met Leu Gly Arg Gin Gin Ile Ala Giy Ile Pro Thr Ala Leu Ser Giu Leu Phe Lys Phe Phe Arg Asn Ala His Asp Ala Ala Asp Asn Val Glu Val Asp Gly Leu Gly Lys Glu Asn Leu Ile Leu Arg Asp Met Thr Thr Asp Giu Phe Glu 55 Giu Arg Trp Leu Thr lie Giy Thr Ser Ser Lys Leu Ile Asp Asp Ala lie Asn Pro Ala Val Asp Ser Asn Lys Ala Phe Pro Ile Met Gly Glu Lys Gly Ile Gly Arg Leu Ser Ile Ala Arg Asp Asn 115 Ile Gly Pro Gin Leu Val Leu Thr Arg Ala Lys 110 Asn Trp Ser Glu Leu Lys Pro Leu 120 Val Ala Ala Phe Val 125 Leu Phe 130 Ala Ile Pro Ser Asp Leu Asp Asp Ile Giu Ile Pro 140 Lys Thr Leu Asp Ile Glu 160 A.rg 145 Met Thr Ile Ile Asn Ile Giu Gin Ala 165 Asp 150 Glu Cys Phe Thr Lys 155 Arg Asn Asn Leu Ser Leu Ser His Lys Ile 175 Sex Lys Sex Phe Asp Pro 195 Lys 180 Vai Ser Gin Ile Asn 185 Thr Gin Leu Ser Ser Phe Glu 190 Arg Leu Sex Ile Leu Trp Glu Lys 200 Lys Leu Gly Gly Leu 205 Giy Asp 210 Gly His Gly Thr His 215 Phe Ile Ile Met Pro 220 Thr Giu Giu Ile Leu 225 Ser Ile Asp Asp Ile Ser Arg Leu Giu 245 Sex 230 Thr Ser Asp Ser Asn 235 Lys Thr Ser Glu Gin 240 Lys Ala Leu Leu Giy 250 Phe Thr Asn Thr Met Tyr 255 Ser Asp Sex Asn 260 Pro Pro Ile Ile Ala 265 Arg Phe Arg Asp Tyr Leu Glu 270 Asp Giy Giu Cys Ile Asp Arg le Ser Glu Ser Ile Phe Phe Thr Pro 280 285 Trp Gin Glu 290 Phe Gly Asn Leu Ala Asp 295 Thr His Ile Glu Phe Asn Glu Gln Phe Ser 305 His Giy 310 Trp Val Ser Val Tyr 315 Gin Glu Glu Pro His Val Val Thr 325 Lys Lys Asn Asn Leu Thr Gin Cys Gly 335 Pro Phe Lys Arg Leu Pro 355 Tyr Gly Gly Ile 340 Met Leu Ala Tyr Ile 345 Pro Gly Arg Leu Glu Leu Trp Ala 360 Arg Leu Lys Glu Arg Asp Ser 350 Thr Asp Arg Leu Pro Tyr Leu Tyr Ile 370 Gly Asp Tyr 375 Phe Asp Giy Leu Ser Asp Thr 385 Ser Asp 390 Phe Leu Lys Ile Giu 395 Arg Arg Arg Thr Leu 400 Ala Ser Glu Tyr 405 Glu Phe Ser Tyr Arg 410 Leu Leu Phe Gly Ala Ile 415 Glu Leu Thr Glu Giy Phe 435 Glu Asn Phe Asn Asn Ala Ser 425 Tyr Val Giu Lys Glu Asn Lys Pro 440 Ala Lys Gin Phe Ala Gly Arg 430 Glu Met Leu Asp Asp Gly Phe Ile Glu 450 Asp Met Ile 455 Val Arg Asp Phe Phe 460 Arg Ser Giu Leu 465 His Phe 470 Lys Glu Thr Lys Gln 475 Thr Arg Asn Glu Glu 480 Asp Leu Leu Ser 485 Asp Arg Ser Lys Lys Ala Lys Lys Asp 495 Arg Leu Lys Tyr Trp Asn 515 Lys 500 Ile Leu Tyr Asp Phe 505 Leu Asp Lys Leu Asp Asn Asp 510 Glu Giu Tyr Glu lie Asn Lys 520 Lie Asn Lys Phe Ser 530 Ser Thr Glu Ile Asp Thr Asn Ile Tyr Val Tyr Asn Lys 545 Ile Lys Giu Gln Asp Aia Ile Ile Lys 555 Asn Leu Axg Asn Val Asp Ile Lys Pro Ser Gly Val Leu Thr Lys Glu Leu Ser 575 Asn Leu Trp Leu Asn Glu 595 Asp 580 Arg Tyr Gin Ile Glu 585 Arg Gln Lys Ile Leu Leu Ser 590 Glu Leu Asp Leu Lys Asp Asn Asp Arg Lys Leu Asn Lys 610 Asn Asn Asp Phe Asn Leu Arg Lys Leu Glu Asp Ser Leu 625 Asn Asn Leu Gin Gln Asp Ala Lys Asn 645 Ser 630 Tyr Tyr Giu Lys Leu Thr Lys Leu Ala Leu Lys Asp Gin Ser Lys Ala Asn Arg 655 Leu Ile Ser Ser Tyr Glu 675 Asp 660 Asn Lys Lys Lys His 665 Lys Ser Giu Leu Lys Asn Ile 670 Thr Ala Tyr Phe Gin Ser Thr Asn 680 Leu Asn Giy Lys Ile Leu 690 Asp Vai Lys Arg Asn 695 Leu Giu Ser Lys Ile 700 Glu Asn Thr Ser Asn 705 Glu Val Ile Asn Ile Arg Lys Leu Thr 715 Asp Gin Ile Ala Ile Ser Asp Ser Thr 725 Thr Ser Giu Asn Leu 730 Ser Ser Ala Gln Val Thr 735 Glu Ala Ile Asn Ala Glu 755 Glu 740 Thr Giu Leu Glu His 745 Leu Arg Asp Gin Gin Ala Asn 750 Val His His Leu Ile Leu Leu Gly 760 Met Ala Leu Ser Val 765 Glu Phe 770 Asn Gy Asn Ile Arg 775 Ala Ile Arg Ser Ala 780 Leu Arg Giu Leu Lys 785 Al1a Trp Ala Asp A.rg Asn 790 Pro Lys Leu Asp 795 Ile Ile Tyr Gin Lys 800 Phe Thr 815 Ile Arg Thr Ser Asp His Leu Asp Tyr Leu Lys Thr Pro Leu Thr Ala Ile Leu 835 Arg 820 Arg Leu Ser Arg Ser 825 Lys Thr Asn Ile Thr Gly Thr 830 Leu Giu Lys Giu Phe Ile Arg Asp Val Phe Asp Asp 840 Axrg 845 GiU Gly 850 Ile Giu Leu Phe Thr 855 Thr.Ser Lys Phe Vai 860 Asn Gin Glu Ile Val 865 Thr Tyr Thr Ser Thr 870 Ile Tyr Pro Val Phe 8-75 Ile Asn Leu Ile Asn Ala Ile Tyr Leu Giy Lys Thr Gly Giu Lys Arg Leu Ile 895 Leu Asp Ala Val Ser Thr 915 Thr 900 Giu Thr Gly Phe Val 905 Ile Gly Asp Thr Gly Pro Gly 910 Phe Thr Arg Arg Asp Arg Asp Ile Phe Asp Met Gi y 925 Lys Thr 930 Giy Gly Arg Gly Met 935 Giy Leu Phe Ile Ser Lys Giu Cys Leu 940 Tyr Thr Pro Giu Gin Ser 945 Gly A.rg Asp Giy Phe Ala Phe Phe Ile 965 Thr 950 Ile Arg Leu Asp Asp 955 Ile Giu Pro Ser Giu Thr Ser Giu <210> <211> 555 <212> PRT <213> Escherichia ci <400> Met Thr Ser Ser Thr Asp Phe His 1 5 Azg Phe Leu His Ser Val Val. Ala Lys Leu Ser Giu Asp Cys Vai Arg 10 Val Asp Asp Asn Met Ser Phe Gly 25 Ala Gly Ser Asp Thr Phe Pro Thr Asp Giu Asp Ile Asn Ala Leu Val Asp Asp Asp Pro Asp Pro Thr Pro Ile Ile Thr Ser Ala Ser Pro Arg Ile Giu Ser Thr Ser Lys Ala Lys Val 75 Lys Asn His Pro Phe Asp Tyr Gin Ala Leu Ala Glu Ala Phe Lys Asp Gly lle Ala Cys Cys Gly Leu Thr Ala Ser 115 Ala Lys Ser Phe Asn 105 Val Giu Giu Arg Asp Ile Ile 110 Trp Asp Met Ser His Lys Ala Ile Thr Ile Leu Gin Ser 130 Asp Ser Gly Gin Phe 135 Ala Ile Giu Ile lie 140 Lys Ser Ile Ile Val 145 Ser Asp Ile Asn Gly Gly Arg Leu Leu Leu Ser Ile Tyr 160 Thr Gly Giu His Val 165 Thr Ala Val Ile Thr 170 Lys Leu Asn Asn Glu Leu 175 Lys Lys Thr Giu Asp Asn 195 Tyr 180 Arg Ser Val Ile Lys Asn Asp Asp Ser 185 Trp Cys Ile Val Vai 205 Ile Phe Ile 190 Lie Ser Lys Tyr Ala Leu Glu Gln 200 Asp Val 210 Tyr Giu Lys Asp Leu 215 Pro Asn Vai Leu Ile Lys Lys Phe 220 Leu Ser Cys Ile Thr Ser As 225 Glu Leu Thr Ala Giy Ile Arg Giu Lys 245 Leu Ser Asn Ala Ala 235 240 Asn Lys 255 Thr His Giy Ile Leu 250 Thr Lys Tyr Asn Leu Asp Thr Glu Ser Arg 275 Ala 260 Tyr Vai Ser His Ile 265 Leu Asn Leu Ile Lys Ser Lys 270 Ala Vai Asp Ala Tyr Ala Tyr Glu 280 Asn Ala His Asp Tyr 285 Leu Ile 290 Ser Giu Giu Ile Arg 295 Ser Ile Leu Gln Ser Giu Asn Leu Lys Ser Leu Ser Lys 310 Asn Ser Leu Ser His 315 Trp Pro Ile Phe His 320 Tyr Aia Lys Asn Cys Lys Asn Phe Leu 330 Leu Thr Giy Lys Lys Gin 335 LyS Asp Leu Leu Giu Glu 355 Val Giu His Leu Ag 315 Asn Ile Leu Ser Ala Asp Ser 350 Giy Lys Lys Ile Gin His Ala Glu His Ala Ser Glu Tyr 370 Leu Ser Gin Asp Gly 375 Glu Giu Asp Lys Lys 380 Leu Met Gin Leu cys 385 Ser Leu Giu Ile Thr 390 Arg Arg Ser Leu Tyr His Ser His Asp Asn Val Sex Lys Gin Giy Thr Leu 410 Leu Leu Asp Ala Tyr Asn 415 Phe Vai Tyr Glu Lys Ala 435 Leu 420 Cys Ile Gin Pro Cys Asp Ser Vai Arg Leu His 430 Asp Phe Leu Phe Leu 440 Arg Gly Thr Leu Asp Asp Asn Asn 445 Tyr Asn 450 Leu Leu Ile Glu Asp 455 Glu Tyr Giy Gly Ph. 460 Tyr Lys Ile Lys Met 465 Asn Pro Ala Lys Ala Giy Asn Giy Vai 485 Ser 470 Asn Ile Ile Ser Phe 475 Ser Ph. Giy Val lie Ile Giy Lys Lys 490 Asn Asn Leu Val Asn Thr 495 Asp Tyr Ile Lys Vai Leu 515 Ser 500 Ph. Val Pro Leu Leu 505 Val Giu Lys Ile Ser Thr Pro 510 Ala Gin Lys Lys Trp Ile Gly Glu 520 Ile Lys Thr Thr Tyr 525 Ile Thr Thr Asp Ile Vai Ala Asn Leu Ser Arg 530 535 Ile 540 Gly Leu Asp Gin His Giu Trp, Leu Arg Ile Lys Ser Lys Asp Ile 545 550 555 <210> 46 <211> 82 <212> PRT <213> Escherichia coli <400> 46 met Ser Ser Arg Gin Ile Leu Giu His Tyr Asn Ala Leu Thr Tyr Pro 1 5 10 Leu His Gin Vai Cys Thr Ile Leu Leu Gin Met Thr Ser Asn Leu Leu Ser Ser Ser Trp Gly Lys Ser Ile Tyr 40 Giu Asp Ile Ser Giy Asn Ile Ile His Phe Asn Ile 55 Pro Leu Pro Ile Ser Arg Ala.Arg Trp Met Ser Met Leu Asp Ser Ile Phe Ser Tyr Val Arg Ile Lys Tyr Met <210> 47 <211> 98 <212> PRT <213> Escherichia coi <400> 47 Met Ser Ile Ilie I Ile Thr Giu Ala Val Val Gly Arg Phe Val Arg Phe Phe Asn Gly His Tyr Arg Met Lys His Arg Thr Trp Leu Arg Leu His Giu Giu His Leu Pro Gin Val Cys Gly Met Arg Leu Gly Arg Lys Ala Pro Lys Ser Thr Ala Giy Phe Ser Trp Leu Pro Ala Gly Met .Ser Giu Arg Glu Leu Asp Gly Arg Leu Tyr GlIy Ser Thr Ser Thr '7 Val Pro Val Val Leu Cys Ser Gly Ser Val Ile Gin Asp Thr Ser Lys 90 Ser Cys <210> 48 <211> 106 <212> PRT <213> Escherichia coli <400> 48 Met Ile Lys Thr Arg 1 Arg Thr Lys Arg Thr Phe Ser Pro Giu Phe Lys Leu Giu Ala Giu Val Ala Phe Giu Gin Val Val Val 25 Lys Tyr Gin Arg Asp Val Arg Arg Lys Trp, Gin Ala Leu Giu Asn Pro Asp His Leu Ile Arg Leu Tyr Lys Gin Leu Gin Giy Ile Pro Ala Gly Asn Al a Ile Thr Pro Giu Arg Giu Ile Gin Gin 75 Leu Lys Ala Gin Ile Lys Arg Val Glu Met Glu Lys Giu Ile Leu 90 Lys Gin Ala Ala Val Leu Met Ser Giu Ile 100 Pro Gly Lys Leu Ser Arg 105 <210> 49 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucieotide <400> 49 tgctctagag ccattactca gaatggg 27 <210> <211> 26 <212> DNA 00 <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide tr~ <400> cgcgagctcg acgactgaatgcc 26 <210> 51 CKI<211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> 51 tcccccgggt actgcagcac icaacc 26 <210> 52 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <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 tggagcg 27 CK1 <210> 54 <211> 28 <212> DNA 00 <213> Artificial Sequence <220> <223> Description of Artificial Sequerice:Oligonucleotide <400> 54 gaactgcagc caaatactga taccaccc 28 <210> CK1<211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> gaactgcagg ctaaaacaga agacgcg 27 <210> 56 <211> 27 (212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <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 <212> DNA <213> Artificial Sequence .00 <220> <223> Description of Artificial Sequence: Oligonucleotide tfl<400> 58 caactgcagt cgcaaattgc gaactgg 27 <210> 59 ri<21.1> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 59 caactgcaga ccgcaacttt tcgacgc 27 <210> <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> catgcatgcc agtgagccat tgttccc 27 <210> 61 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 61 tgctctagat acgactctga caggagg 27 100 <210> 62 <211> 26 <212> DNA <213> Artificial Sequence 00 <220> <223> Description of Artificial Sequence:Oligoriucleotide <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> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> 64 tgctctagaa aacgtggcaa cagagcg 27 <210> <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:Oligonucleotide <400> tgctctagaa ggcgttgtcg atcctg 26 <210> 66 <211> 28 <212> DNA <213> Artificial Sequence 00 <220> <223> Description of Artificial sequence: Oligonucleotide <400> 66 gaatgcggaaaaggccga gcagactg 2 <210> 67 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligoriucleotide <400> 67 gaactgcagi acagccatgt ttacggt 27 <210> 68 <211> 27 <212> DNA <213> Artificial sequence <220> <223> Description of Artificial Sequence:oligonucleotide <400> 68 catgcatgcg gtgtacgaca gtttgcg 27 <210> 69 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:0ligonucleotide <400> 69 tgctctagac acatcatggg cacacc 26 <210> <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial sequence: Oligonucleotide <400> gaactgcaga accgtccaca tcaggcg 27 <210> 71 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Oligonucleotide <400> 71 gaactgcaga ccctgcttgc cattceg 27 <210> 72 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence:oligonucleotide <400> 72 catgcatgca taagcgtcga acaggcg 27