TOBZ_STRSD
ID TOBZ_STRSD Reviewed; 570 AA.
AC Q70IY1; Q2MF18;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=nebramycin 5' synthase;
DE EC=6.1.2.2;
DE AltName: Full=Kanamycin A carbamoyltransferase;
DE AltName: Full=Tobramycin carbamoyltransferase;
GN Name=tobZ; Synonyms=tacA;
OS Streptoalloteichus tenebrarius (strain ATCC 17920 / DSM 40477 / JCM 4838 /
OS CBS 697.72 / NBRC 16175 / NCIMB 11028 / NRRL B-12390 / A12253. 1)
OS (Streptomyces tenebrarius).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Streptoalloteichus.
OX NCBI_TaxID=1933;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 17920 / DSM 40477 / JCM 4838 / CBS 697.72 / NBRC 16175 / NCIMB
RC 11028 / NRRL B-12390 / A12253. 1;
RX PubMed=14757238; DOI=10.1016/s0378-1097(03)00881-4;
RA Kharel M.K., Basnet D.B., Lee H.C., Liou K., Woo J.S., Kim B.-G.,
RA Sohng J.K.;
RT "Isolation and characterization of the tobramycin biosynthetic gene cluster
RT from Streptomyces tenebrarius.";
RL FEMS Microbiol. Lett. 230:185-190(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 17920 / DSM 40477 / JCM 4838 / CBS 697.72 / NBRC 16175 / NCIMB
RC 11028 / NRRL B-12390 / A12253. 1;
RA Aboshanab K., Schmidt-Beissner H., Wehmeier U., Welzel K., Vente A.,
RA Piepersberg W.;
RT "Comparison of the gene clusters for the biosynthesis of the aminoglycoside
RT antibiotics tobramycin-apramycin (Streptomyces tenebrarius DSM 40477), and
RT hygromycin B (Streptomyces hygroscopicus subsp. hygroscopicus DSM 40578).";
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H6;
RX PubMed=20936279; DOI=10.1007/s00253-010-2908-5;
RA Ni X., Li D., Yang L., Huang T., Li H., Xia H.;
RT "Construction of kanamycin B overproducing strain by genetic engineering of
RT Streptomyces tenebrarius.";
RL Appl. Microbiol. Biotechnol. 89:723-731(2011).
RN [4] {ECO:0007744|PDB:3VEN, ECO:0007744|PDB:3VEO, ECO:0007744|PDB:3VER, ECO:0007744|PDB:3VES, ECO:0007744|PDB:3VET, ECO:0007744|PDB:3VEW, ECO:0007744|PDB:3VEX, ECO:0007744|PDB:3VEZ, ECO:0007744|PDB:3VF2, ECO:0007744|PDB:3VF4}
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF WILD-TYPE AND MUTANTS ASN-14;
RP ALA-443; ILE-473 AND ALA-530 IN COMPLEXES WITH ATP, ADP; CARBAMOYL
RP ADENYLATE; CARBAMOYL PHOSPHATE; TOBRAMYCIN AND IRON ION, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF HIS-14; LYS-443; MET-473
RP AND SER-530, ACTIVITY REGULATION, REACTION MECHANISM, COFACTOR, AND
RP SUBSTRATE SPECIFICITY.
RX PubMed=22383337; DOI=10.1002/anie.201108896;
RA Parthier C., Gorlich S., Jaenecke F., Breithaupt C., Brauer U.,
RA Fandrich U., Clausnitzer D., Wehmeier U.F., Bottcher C., Scheel D.,
RA Stubbs M.T.;
RT "The O-carbamoyltransferase TobZ catalyzes an ancient enzymatic reaction.";
RL Angew. Chem. Int. Ed. 51:4046-4052(2012).
CC -!- FUNCTION: TobZ is involved in the biosynthesis of the 2-
CC deoxystreptamine-containing aminoglycoside antibiotics such as
CC nebramycin 5 and 6-O-carbamoylkanamycin. Catalyzes the hydrolysis of
CC carbamoyl phosphate and its subsequent adenylation by ATP to yield O-
CC carbamoyladenylate. Then it catalyzes the transfer of the carbamoyl
CC moiety from O-carbamoyladenylate to the tobramycin 6-hydroxy group to
CC yield nebramycin 5'. It catalyzes the same reaction with kanamycin A.
CC These reactions are considerably slower in the presence of deoxy-ATP.
CC {ECO:0000269|PubMed:20936279, ECO:0000269|PubMed:22383337}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + carbamoyl phosphate + H2O + tobramycin = AMP +
CC diphosphate + H(+) + nebramycin 5' + phosphate; Xref=Rhea:RHEA:42096,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228,
CC ChEBI:CHEBI:73678, ChEBI:CHEBI:73679, ChEBI:CHEBI:456215; EC=6.1.2.2;
CC Evidence={ECO:0000269|PubMed:22383337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42097;
CC Evidence={ECO:0000305|PubMed:22383337};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + carbamoyl phosphate + H2O + kanamycin A = 6''-O-
CC carbamoylkanamycin A + AMP + diphosphate + H(+) + phosphate;
CC Xref=Rhea:RHEA:42100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58214, ChEBI:CHEBI:58228, ChEBI:CHEBI:73675,
CC ChEBI:CHEBI:456215; EC=6.1.2.2;
CC Evidence={ECO:0000269|PubMed:22383337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42101;
CC Evidence={ECO:0000305|PubMed:22383337};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + carbamoyl phosphate + H2O = carbamoyl adenylate +
CC diphosphate + phosphate; Xref=Rhea:RHEA:36375, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58228, ChEBI:CHEBI:73674;
CC Evidence={ECO:0000269|PubMed:22383337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36376;
CC Evidence={ECO:0000305|PubMed:22383337};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl adenylate + tobramycin = AMP + H(+) + nebramycin 5';
CC Xref=Rhea:RHEA:36383, ChEBI:CHEBI:15378, ChEBI:CHEBI:73674,
CC ChEBI:CHEBI:73678, ChEBI:CHEBI:73679, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:22383337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36384;
CC Evidence={ECO:0000305|PubMed:22383337};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl adenylate + kanamycin A = 6''-O-carbamoylkanamycin A
CC + AMP + H(+); Xref=Rhea:RHEA:36387, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58214, ChEBI:CHEBI:73674, ChEBI:CHEBI:73675,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:22383337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36388;
CC Evidence={ECO:0000305|PubMed:22383337};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:22383337};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:22383337};
CC -!- ACTIVITY REGULATION: ADP inhibits the formation of nebramycin 5'.
CC {ECO:0000269|PubMed:22383337}.
CC -!- PATHWAY: Antibiotic biosynthesis; kanamycin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; tobramycin biosynthesis.
CC -!- DOMAIN: Consists of two major domains: the N-terminal domain (Kae1-
CC like) is involved in the transfer of carbamoyl from O-
CC carbamoyladenylate to tobramycin or kanamycin; the C-terminal domain
CC (YrdC-like) is involved in the hydrolysis of carbamoyl phosphate and
CC its subsequent adenylation by ATP.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene accumulate kanamycin.
CC {ECO:0000269|PubMed:20936279}.
CC -!- MISCELLANEOUS: It seems that TobZ plays a solely passive role in the
CC adenylation reaction: all functional groups appear to be provided by
CC the substrates themselves, representing an extreme form of substrate-
CC assisted catalysis. The role of the iron in catalysis remains unclear
CC (PubMed:22383337). {ECO:0000305|PubMed:22383337}.
CC -!- SIMILARITY: Belongs to the NodU/CmcH family. {ECO:0000305}.
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DR EMBL; AJ579650; CAE22473.1; -; Genomic_RNA.
DR EMBL; AJ810851; CAH18554.1; -; Genomic_DNA.
DR PDB; 3VEN; X-ray; 1.57 A; A=1-570.
DR PDB; 3VEO; X-ray; 2.19 A; A=1-570.
DR PDB; 3VER; X-ray; 2.34 A; A=1-570.
DR PDB; 3VES; X-ray; 2.23 A; A=1-570.
DR PDB; 3VET; X-ray; 2.20 A; A=1-570.
DR PDB; 3VEW; X-ray; 2.35 A; A=1-570.
DR PDB; 3VEX; X-ray; 1.90 A; A=1-570.
DR PDB; 3VEZ; X-ray; 2.40 A; A=1-570.
DR PDB; 3VF2; X-ray; 2.90 A; A=1-570.
DR PDB; 3VF4; X-ray; 2.40 A; A=1-570.
DR PDBsum; 3VEN; -.
DR PDBsum; 3VEO; -.
DR PDBsum; 3VER; -.
DR PDBsum; 3VES; -.
DR PDBsum; 3VET; -.
DR PDBsum; 3VEW; -.
DR PDBsum; 3VEX; -.
DR PDBsum; 3VEZ; -.
DR PDBsum; 3VF2; -.
DR PDBsum; 3VF4; -.
DR AlphaFoldDB; Q70IY1; -.
DR SMR; Q70IY1; -.
DR PRIDE; Q70IY1; -.
DR KEGG; ag:CAE22473; -.
DR BioCyc; MetaCyc:MON-17235; -.
DR UniPathway; UPA00965; -.
DR UniPathway; UPA00971; -.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016743; F:carboxyl- or carbamoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:1901133; P:kanamycin biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901121; P:tobramycin biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.90.870.20; -; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR031730; Carbam_trans_C.
DR InterPro; IPR038152; Carbam_trans_C_sf.
DR InterPro; IPR003696; Carbtransf_dom.
DR Pfam; PF16861; Carbam_trans_C; 1.
DR Pfam; PF02543; Carbam_trans_N; 2.
DR SUPFAM; SSF53067; SSF53067; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; ATP-binding; Hydrolase; Iron;
KW Ligase; Metal-binding; Nucleotide-binding.
FT CHAIN 1..570
FT /note="nebramycin 5' synthase"
FT /id="PRO_0000425806"
FT REGION 1..354
FT /note="Kae1-like"
FT REGION 367..570
FT /note="YrdC-like"
FT ACT_SITE 14
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:22383337"
FT BINDING 12
FT /ligand="tobramycin"
FT /ligand_id="ChEBI:CHEBI:73678"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEZ"
FT BINDING 114
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 118
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 137
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 139
FT /ligand="carbamoyl adenylate"
FT /ligand_id="ChEBI:CHEBI:73674"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEX"
FT BINDING 168
FT /ligand="carbamoyl adenylate"
FT /ligand_id="ChEBI:CHEBI:73674"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEX"
FT BINDING 172
FT /ligand="carbamoyl adenylate"
FT /ligand_id="ChEBI:CHEBI:73674"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEX"
FT BINDING 172
FT /ligand="tobramycin"
FT /ligand_id="ChEBI:CHEBI:73678"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 228
FT /ligand="tobramycin"
FT /ligand_id="ChEBI:CHEBI:73678"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 310
FT /ligand="carbamoyl adenylate"
FT /ligand_id="ChEBI:CHEBI:73674"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEX"
FT BINDING 314
FT /ligand="carbamoyl adenylate"
FT /ligand_id="ChEBI:CHEBI:73674"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEX"
FT BINDING 338
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 418..419
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 418
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEZ"
FT BINDING 449
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VEZ"
FT BINDING 498
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT BINDING 528..530
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000269|PubMed:22383337,
FT ECO:0007744|PDB:3VET"
FT MUTAGEN 14
FT /note="H->N: Shows negligible tobramycin carbamoylation
FT activity."
FT /evidence="ECO:0000269|PubMed:22383337"
FT MUTAGEN 443
FT /note="K->A: The nucleotide binds in a similar fashion to
FT ACP in wild-type, but the positions of the beta- and gamma-
FT phosphorus atoms are shifted, so that the magnesium ion no
FT longer coordinates the gamma-phosphate and the mutant is
FT unable to catalyze the adenylation."
FT /evidence="ECO:0000269|PubMed:22383337"
FT MUTAGEN 473
FT /note="M->I: Binds carbamoyl phosphate, but not nucleotide,
FT so that the mutant is unable to catalyze the adenylation."
FT /evidence="ECO:0000269|PubMed:22383337"
FT MUTAGEN 530
FT /note="S->A: Binds carbamoyl phosphate, but not nucleotide,
FT so that the mutant is unable to catalyze the adenylation."
FT /evidence="ECO:0000269|PubMed:22383337"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 17..22
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 32..36
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:3VET"
FT HELIX 47..57
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:3VEX"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 140..151
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 154..162
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 200..204
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 230..244
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 261..269
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 275..300
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 303..309
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 315..322
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:3VEX"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 341..352
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 372..382
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 392..401
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 421..430
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 434..440
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 441..443
FT /evidence="ECO:0007829|PDB:3VF4"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 457..463
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 484..486
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 488..490
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 495..497
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 500..502
FT /evidence="ECO:0007829|PDB:3VEN"
FT TURN 504..506
FT /evidence="ECO:0007829|PDB:3VEN"
FT HELIX 508..521
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 525..532
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:3VEZ"
FT HELIX 542..551
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 555..559
FT /evidence="ECO:0007829|PDB:3VEN"
FT STRAND 562..565
FT /evidence="ECO:0007829|PDB:3VEN"
SQ SEQUENCE 570 AA; 62547 MW; 88C6B6E44CC00546 CRC64;
MRVLGLNGWP RDFHDASAAL LVDGRIAAFA EEERFTRKKH GYNTAPVQAA AFCLAQAGLT
VDDLDAVAFG WDLPAMYRER LGGWPHSDSE ALDILLPRDV FPRRTDPPLH FVQHHLAHAA
SAYYFSGEDR GAVLIVDGQG EEECVTLAHA EGGKITVLDT VPGAWSLGFF YEHVSEYTGL
GGDNPGKLMG LAAHGTTVDE TLSAFAFDSD GYRLNLIDPQ ARDPEDWDEY SVTERAWFAH
LERIYRLPPN EFVRRYDPAK GRVVRDTRRD PYEYRDLAAT AQAALERAVF GLADSVLART
GERTLFVAGG VGLNATMNGK LLTRSTVDKM FVPPVASDIG VSLGAAAAVA VELGDRIAPM
GDTAAWGPEF SPDQVRAALD RTGLAYREPA NLEREVAALI ASGKVVGWAQ GRGEVGPRAL
GQRSLLGSAH SPTMRDHINL RVKDREWWRP FAPSMLRSVS DQVLEVDADF PYMIMTTKVR
AAYAERLPSV VHEDWSTRPQ TVTEASNPRY HRMLTELGDL VGDPVCLNTS FNDRGEPIVS
SPADALLTFS RLPIDALAVG PYLVTKDLRH
