ID   METH_SALTY              Reviewed;        1227 AA.
AC   P37586;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 160.
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=STM4188;
OS   Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Salmonella.
OX   NCBI_TaxID=99287;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX   PubMed=11677609; DOI=10.1038/35101614;
RA   McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA   Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA   Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA   Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA   Wilson R.K.;
RT   "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL   Nature 413:852-856(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-371.
RC   STRAIN=LT2;
RX   PubMed=3072256; DOI=10.1016/0378-1119(88)90325-3;
RA   Urbanowski M.L., Stauffer G.V.;
RT   "The control region of the metH gene of Salmonella typhimurium LT2: an
RT   atypical met promoter.";
RL   Gene 73:193-200(1988).
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAL23012.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AE006468; AAL23012.1; ALT_INIT; Genomic_DNA.
DR   RefSeq; NP_463053.3; NC_003197.2.
DR   RefSeq; WP_014343933.1; NC_003197.2.
DR   AlphaFoldDB; P37586; -.
DR   SMR; P37586; -.
DR   STRING; 99287.STM4188; -.
DR   PaxDb; 99287-STM4188; -.
DR   GeneID; 1255714; -.
DR   KEGG; stm:STM4188; -.
DR   PATRIC; fig|99287.12.peg.4402; -.
DR   HOGENOM; CLU_004914_2_2_6; -.
DR   PhylomeDB; P37586; -.
DR   UniPathway; UPA00051; UER00081.
DR   PHI-base; PHI:8092; -.
DR   Proteomes; UP000001014; Chromosome.
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:0050667; P:homocysteine metabolic process; IBA:GO_Central.
DR   GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0046653; P:tetrahydrofolate metabolic process; IBA:GO_Central.
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   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..1227
FT                   /note="Methionine synthase"
FT                   /id="PRO_0000204536"
FT   DOMAIN          2..325
FT                   /note="Hcy-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   DOMAIN          356..617
FT                   /note="Pterin-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT   DOMAIN          650..744
FT                   /note="B12-binding N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT   DOMAIN          746..881
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT   DOMAIN          897..1227
FT                   /note="AdoMet activation"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT   BINDING         247
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   BINDING         310
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         694
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         756..760
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         759
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         804
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         808
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         860
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         946
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         1134
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         1189..1190
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        115
FT                   /note="A -> R (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1227 AA;  136004 MW;  11C8E21745FF5354 CRC64;
     MSSKVEQLRA QLNERILVLD GGMGTMIQSY RLHEEDFRGE RFADWPCDLK GNNDLLVLSK
     PEVIAAIHNA YFEAGADIIE TNTFNSTTIA MADYRMESLS AEINYAAAKL ARACADEWTA
     RTPEKPRFVA GVLGPTNRTA SISPDVNDPA FRNITFDQLV AAYRESTKAL VEGGADLILI
     ETVFDTLNAK AAVFAVKEEF EALGVDLPIM ISGTITDASG RTLSGQTTEA FYNSLRHAEA
     LTFGLNCALG PDELRQYVQE LSRIAECYVT AHPNAGLPNA FGEYDLDADT MAKQIREWAE
     AGFLNIVGGC CGTTPEHIAA MSRAVAGLLP RQLPDIPVAC RLSGLEPLNI GDDSLFVNVG
     ERTNVTGSAK FKRLIKEEKY SEALDVARQQ VESGAQIIDI NMDEGMLDAE AAMVRFLSLI
     AGEPDIARVP IMIDSSKWEV IEKGLKCIQG KGIVNSISMK EGVEAFIHHA KLLRRYGAAV
     VVMAFDEQGQ ADTRARKIEI CRRAYKILTE EVGFPPEDII FDPNIFAVAT GIEEHNNYAQ
     DFIGACEDIK RELPHALISG GVSNVSFSFR GNDPVREAIH AVFLYYAIRN GMDMGIVNAG
     QLAIYDDLPA ELRDAVEDVI LNRRDDGTER LLDLAEKYRG SKTDEAANAQ QAEWRSWDVK
     KRLEYSLVKG ITEFIEQDTE EARQQAARPI EVIEGPLMDG MNVVGDLFGE GKMFLPQVVK
     SARVMKQAVA YLEPFIEASK EKGSSNGKMV IATVKGDVHD IGKNIVGVVL QCNNYEIVDL
     GVMVPAEKIL RTAREVNADL IGLSGLITPS LDEMVNVAKE MERQGFTIPL LIGGATTSKA
     HTAVKIEQNY SGPTVYVQNA SRTVGVVAAL LSDTQRDDFV ARTRKEYETV RIQHARKKPR
     TPPVTLEAAR DNDLAFDWER YTPPVAHRLG VQEVEASIET LRNYIDWTPF FMTWSLAGKY
     PRILEDEVVG VEAQRLFKDA NDMLDKLSAE KLLNPRGVVG LFPANRVGDD IEIYRDETRT
     HVLTVSHHLR QQTEKVGFAN YCLADFVAPK LSGKADYIGA FAVTGGLEED ALADAFEAQH
     DDYNKIMVKA IADRLAEAFA EYLHERVRKV YWGYAPNESL SNDELIRENY QGIRPAPGYP
     ACPEHTEKGT IWQLLDVEKH TGMKLTESFA MWPGASVSGW YFSHPESKYF AVAQIQRDQV
     TDYAFRKGMS VEDVERWLAP NLGYDAD
//