METH_VIBCH
ID METH_VIBCH Reviewed; 1226 AA.
AC Q9KUW9;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 122.
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=VC_0390;
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
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; AE003852; AAF93563.1; -; Genomic_DNA.
DR PIR; E82328; E82328.
DR RefSeq; NP_230044.1; NC_002505.1.
DR RefSeq; WP_000514261.1; NZ_LT906614.1.
DR AlphaFoldDB; Q9KUW9; -.
DR SMR; Q9KUW9; -.
DR STRING; 243277.VC_0390; -.
DR DNASU; 2614987; -.
DR EnsemblBacteria; AAF93563; AAF93563; VC_0390.
DR GeneID; 57739129; -.
DR KEGG; vch:VC_0390; -.
DR PATRIC; fig|243277.26.peg.365; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_2_2_6; -.
DR OMA; ADCIAMS; -.
DR BioCyc; VCHO:VC0390-MON; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000000584; Chromosome 1.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008705; F:methionine synthase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
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 Gene3D; 1.10.1240.10; -; 1.
DR Gene3D; 3.10.196.10; -; 1.
DR Gene3D; 3.20.20.20; -; 1.
DR Gene3D; 3.20.20.330; -; 1.
DR InterPro; IPR003759; Cbl-bd_cap.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR011005; Dihydropteroate_synth-like.
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 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; SSF47644; SSF47644; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR SUPFAM; SSF56507; SSF56507; 1.
DR SUPFAM; SSF82282; SSF82282; 1.
DR TIGRFAMs; TIGR02082; metH; 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_0000204538"
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; 135793 MW; 5CF4AB07A738D74F CRC64;
MGKEVRQQLE QQLKQRILLI DGGMGTMIQS YKLQEEDYRG ARFVDWHCDL KGNNDLLVLT
QPQIIKEIHS AYLEAGADIL ETNTFNSTTI AMADYDMQSL SAEINFAAAK LAREVADEWT
AKDPSRPRYV AGVLGPTNRT CSISPDVNDP GFRNVTFDGL VEAYSESTRA LIKGGSDLIL
IETIFDTLNA KACAFAVDSV FEELGISLPV MISGTITDAS GRTLSGQTTE AFYNALRHVR
PISFGLNCAL GPDELRQYVE ELSRISECYV SAHPNAGLPN AFGEYDLSAE EMAEHIAEWA
QAGFLNLVGG CCGTTPEHIA AIAKAVEGVK PRALPDLKVE CRLSGLEPLN IGPETLFVNV
GERTNVTGSA RFKRLIKEEQ YDEALDVARE QVENGAQIID INMDEGMLDA EACMVRFLNL
CASEPEISKV PVMVDSSKWE VIEAGLKCIQ GKGIVNSISL KEGKEKFIAQ AKLVRRYGAA
VIVMAFDEVG QADTRERKLE ICRRAYHILV DEVGFPPEDI IFDPNIFAVA TGIDEHNNYA
LDFINAVADI KRELPHAMIS GGVSNVSFSF RGNNYVREAI HAVFLYHCFK HGMDMGIVNA
GQLEIYDNVP LKLREAVEDV ILNRRSDGTE RLLEIAEAYR ENSVGKEEDA SALEWRAWPV
AKRLEHALVK GITEFIVQDT EEARQQASKP LEVIEGPLMD GMNVVGDLFG EGKMFLPQVV
KSARVMKQAV AYLEPFINAQ KSGSTSNGKI LLATVKGDVH DIGKNIVGVV LQCNNFEIID
LGVMVPCEQI LKVAREQNVD IIGLSGLITP SLDEMVHVAK EMERQGFELP LLIGGATTSK
AHTAVKIEQN YHAPVVYVNN ASRAVGVCTS LLSDEQRPGF IERLDLDYER TRDQHARKTP
KSRPVTLEQA RANKAALDWA NYTPPAPAKP GVHVFENIAL ATLRPYIDWT PFFMTWSLMG
KYPAILEHEE VGEEAKRLFH DANALLDKVE REGLLKASGM CALFPAASVG DDIEVYSDES
RTQVAHVLYN LRQQTEKPKG ANYCLSDYVA PKESGKRDWI GAFAVTGGIG ERALADAYKA
QGDDYNAIMI QAVADRLAEA FAEYLHEKVR KEIWGYASDE NLSNDDLIRE RYQGIRPAPG
YPACPEHTEK ATLWQMLNVE ETIGMSLTTS YAMWPGASVS GWYFSHPDSR YFAVAQIQPD
QLHSYAERKG WRLEEAEKWL APNLDA
