ID METH_VIBPA Reviewed; 1226 AA.
AC Q87L95;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 27-MAR-2024, entry version 118.
DE RecName: Full=Methionine synthase;
DE EC=2.1.1.13;
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase;
DE AltName: Full=Methionine synthase, vitamin-B12 dependent;
DE Short=MS;
GN Name=metH; OrderedLocusNames=VP2717;
OS Vibrio parahaemolyticus serotype O3:K6 (strain RIMD 2210633).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=223926;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RIMD 2210633;
RX PubMed=12620739; DOI=10.1016/s0140-6736(03)12659-1;
RA Makino K., Oshima K., Kurokawa K., Yokoyama K., Uda T., Tagomori K.,
RA Iijima Y., Najima M., Nakano M., Yamashita A., Kubota Y., Kimura S.,
RA Yasunaga T., Honda T., Shinagawa H., Hattori M., Iida T.;
RT "Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism
RT distinct from that of V. cholerae.";
RL Lancet 361:743-749(2003).
CC -!- FUNCTION: Catalyzes the transfer of a methyl group from methyl-
CC cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and
CC methionine. Subsequently, remethylates the cofactor using
CC methyltetrahydrofolate (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine =
CC (6S)-5,6,7,8-tetrahydrofolate + L-methionine; Xref=Rhea:RHEA:11172,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57453, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:58199; EC=2.1.1.13;
CC -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
CC -!- DOMAIN: Modular enzyme with four functionally distinct domains. The
CC isolated Hcy-binding domain catalyzes methyl transfer from free
CC methylcobalamin to homocysteine. The Hcy-binding domain in association
CC with the pterin-binding domain catalyzes the methylation of
CC cob(I)alamin by methyltetrahydrofolate and the methylation of
CC homocysteine. The B12-binding domain binds the cofactor. The AdoMet
CC activation domain binds S-adenosyl-L-methionine. Under aerobic
CC conditions cob(I)alamin can be converted to inactive cob(II)alamin.
CC Reductive methylation by S-adenosyl-L-methionine and flavodoxin
CC regenerates methylcobalamin (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: L-homocysteine is bound via the zinc atom.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC family. {ECO:0000305}.
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DR EMBL; BA000031; BAC60980.1; -; Genomic_DNA.
DR RefSeq; NP_799096.1; NC_004603.1.
DR RefSeq; WP_005453805.1; NC_004603.1.
DR AlphaFoldDB; Q87L95; -.
DR SMR; Q87L95; -.
DR GeneID; 1190262; -.
DR KEGG; vpa:VP2717; -.
DR PATRIC; fig|223926.6.peg.2612; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_2_2_6; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000002493; Chromosome 1.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0042558; P:pteridine-containing compound metabolic process; IEA:InterPro.
DR CDD; cd02069; methionine_synthase_B12_BD; 1.
DR CDD; cd00740; MeTr; 1.
DR Gene3D; 3.40.50.280; Cobalamin-binding domain; 1.
DR Gene3D; 1.10.288.10; Cobalamin-dependent Methionine Synthase, domain 2; 1.
DR Gene3D; 3.20.20.20; Dihydropteroate synthase-like; 1.
DR Gene3D; 3.20.20.330; Homocysteine-binding-like domain; 1.
DR Gene3D; 1.10.1240.10; Methionine synthase domain; 1.
DR Gene3D; 3.10.196.10; Vitamin B12-dependent methionine synthase, activation domain; 1.
DR InterPro; IPR003759; Cbl-bd_cap.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR011005; Dihydropteroate_synth-like_sf.
DR InterPro; IPR003726; HCY_dom.
DR InterPro; IPR036589; HCY_dom_sf.
DR InterPro; IPR033706; Met_synthase_B12-bd.
DR InterPro; IPR011822; MetH.
DR InterPro; IPR036594; Meth_synthase_dom.
DR InterPro; IPR000489; Pterin-binding_dom.
DR InterPro; IPR004223; VitB12-dep_Met_synth_activ_dom.
DR InterPro; IPR037010; VitB12-dep_Met_synth_activ_sf.
DR NCBIfam; TIGR02082; metH; 1.
DR PANTHER; PTHR45833; METHIONINE SYNTHASE; 1.
DR PANTHER; PTHR45833:SF1; METHIONINE SYNTHASE; 1.
DR Pfam; PF02310; B12-binding; 1.
DR Pfam; PF02607; B12-binding_2; 1.
DR Pfam; PF02965; Met_synt_B12; 1.
DR Pfam; PF00809; Pterin_bind; 1.
DR Pfam; PF02574; S-methyl_trans; 1.
DR PIRSF; PIRSF000381; MetH; 1.
DR SMART; SM01018; B12-binding_2; 1.
DR SUPFAM; SSF52242; Cobalamin (vitamin B12)-binding domain; 1.
DR SUPFAM; SSF51717; Dihydropteroate synthetase-like; 1.
DR SUPFAM; SSF82282; Homocysteine S-methyltransferase; 1.
DR SUPFAM; SSF56507; Methionine synthase activation domain-like; 1.
DR SUPFAM; SSF47644; Methionine synthase domain; 1.
DR PROSITE; PS50974; ADOMET_ACTIVATION; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
DR PROSITE; PS51337; B12_BINDING_NTER; 1.
DR PROSITE; PS50970; HCY; 1.
DR PROSITE; PS50972; PTERIN_BINDING; 1.
PE 3: Inferred from homology;
KW Amino-acid biosynthesis; Cobalamin; Cobalt; Metal-binding;
KW Methionine biosynthesis; Methyltransferase; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..1226
FT /note="Methionine synthase"
FT /id="PRO_0000204541"
FT DOMAIN 6..326
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 357..618
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 651..745
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 747..882
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 898..1226
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 695
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 757..761
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 760
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /ligand_part="Co"
FT /ligand_part_id="ChEBI:CHEBI:27638"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 805
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 809
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 861
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 948
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1136
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1191..1192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1226 AA; 136218 MW; 2F7A3269FB7C20A9 CRC64;
MGSKVRQQIE AQLKQRILLI DGGMGTMIQG YKLEEQDYRG ERFANWHCDL KGNNDLLVLS
QPQLIKEIHS AYLEAGADIL ETNTFNATTI AMADYEMESL SEEINFAAAK LAREVADEWT
AKTPDKPRYV AGVLGPTNRT CSISPDVNDP GYRNVSFDEL VEAYSESTRA LIRGGADLIL
IETIFDTLNA KACAFAVDSV FEELGVALPV MISGTITDAS GRTLSGQTTE AFYNSLRHVR
PLSFGLNCAL GPDELRPYVE ELSRISESFV SAHPNAGLPN AFGEYDLSPE DMAEHVKEWA
SSGFLNLIGG CCGTTPEHIR QMAQAVEGVT PRALPDLPVA CRLSGLEPLT IEKETLFINV
GERTNVTGSA RFKRLIKEEQ YDEALEVARQ QVENGAQIID INMDEGMLDA QACMVRFLNL
CASEPEISKV PIMVDSSKWE VIEAGLKCIQ GKGIVNSISL KEGKEKFVEQ AKLIRRYGAA
VIVMAFDEVG QAETRTRKLE ICTNAYRILV DEVGFPPEDI IFDPNIFAVA TGIDEHNNYA
VDFIEAVADI KRDLPHAMIS GGVSNVSFSF RGNNYVREAI HAVFLYHCFK NGMDMGIVNA
GQLEIYDNVP EKLREAVEDV VLNRRDDATE RLLDIAAEYA DKGVGKEEDA SALEWRTWPV
AKRLEHALVK GITEFIVADT EEARVNAVKP LEVIEGPLMD GMNVVGDLFG EGKMFLPQVV
KSARVMKQAV AHLEPFINAE KQSGSSNGKI LLATVKGDVH DIGKNIVGVV LQCNNYEIID
LGVMVPCEKI LKVAIEENVD IIGLSGLITP SLDEMVHVAK EMERLNFDLP LLIGGATTSK
AHTAVKIEQN YKNPVVYVNN ASRAVGVCSS LLSDERRPAF IEKLDADYER VRDQHNRKKP
RTKPVTLEQA RANKVAIDWD AYTPPVPAKP GLHIFDDFDV ATLRKYIDWT PFFMTWSLVG
KYPTIFKHEE VGEEAQRLFH DANELLDRVE REGLLKARGI CGLFPAASVG DDIEVYTDES
RTEVAKVLRN LRQQTEKPKG FNYCLSDYIA PKESGKQDWV GAFAVTGGIG ERELADEYKA
QGDDYNAIMI QAVADRLAEA FAEYLHERVR KEIWGYAADE NLSNDELIRE KYQGIRPAPG
YPACPEHTEK GPLWELLNVE ENIGMSLTTS YAMYPGASVS GWYFSHPDSR YFAIAQIQDD
QLESYADRKG WDRIEAEKWL GPNING
//
