METH_SALTY
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 03-AUG-2022, entry version 153.
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; Proteobacteria; 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 AlphaFoldDB; P37586; -.
DR SMR; P37586; -.
DR STRING; 99287.STM4188; -.
DR PaxDb; P37586; -.
DR PRIDE; P37586; -.
DR EnsemblBacteria; AAL23012; AAL23012; STM4188.
DR GeneID; 1255714; -.
DR KEGG; stm:STM4188; -.
DR PATRIC; fig|99287.12.peg.4402; -.
DR HOGENOM; CLU_004914_2_2_6; -.
DR OMA; ADCIAMS; -.
DR PhylomeDB; P37586; -.
DR UniPathway; UPA00051; UER00081.
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: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 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
