ID Q8Z1V6_SALTI Unreviewed; 1227 AA.
AC Q8Z1V6; Q7C5Q3;
DT 01-MAR-2002, integrated into UniProtKB/TrEMBL.
DT 01-MAR-2002, sequence version 1.
DT 27-MAR-2024, entry version 164.
DE RecName: Full=Methionine synthase {ECO:0000256|ARBA:ARBA00013998, ECO:0000256|PIRNR:PIRNR000381};
DE EC=2.1.1.13 {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|PIRNR:PIRNR000381};
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|ARBA:ARBA00031040, ECO:0000256|PIRNR:PIRNR000381};
GN Name=metH {ECO:0000313|EMBL:CAD09193.1};
GN OrderedLocusNames=STY4405 {ECO:0000313|EMBL:CAD09193.1}, t4115
GN {ECO:0000313|EMBL:AAO71579.1};
GN ORFNames=CAJ85_17655 {ECO:0000313|EMBL:EDG8894196.1}, CC907_14095
GN {ECO:0000313|EMBL:EDI0994721.1}, D4Z37_19220
GN {ECO:0000313|EMBL:EBS6527913.1}, DKA88_19520
GN {ECO:0000313|EMBL:EBW2554634.1}, EID90_15005
GN {ECO:0000313|EMBL:EBZ9856156.1}, G2227_07870
GN {ECO:0000313|EMBL:HAE0480808.1}, G2244_19420
GN {ECO:0000313|EMBL:HAE0418666.1}, G3982_003017
GN {ECO:0000313|EMBL:HAE3629351.1}, G4Y55_001796
GN {ECO:0000313|EMBL:HAE9579043.1}, G9C68_001428
GN {ECO:0000313|EMBL:HAF0685916.1}, G9X37_000555
GN {ECO:0000313|EMBL:HAF7360073.1}, GND71_003726
GN {ECO:0000313|EMBL:HAE7811777.1}, K3U68_20810
GN {ECO:0000313|EMBL:QZA29227.1};
OS Salmonella typhi.
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=90370 {ECO:0000313|EMBL:CAD09193.1, ECO:0000313|Proteomes:UP000000541};
RN [1] {ECO:0000313|EMBL:CAD09193.1, ECO:0000313|Proteomes:UP000000541}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CT18 {ECO:0000313|EMBL:CAD09193.1,
RC ECO:0000313|Proteomes:UP000000541};
RX PubMed=11677608; DOI=10.1038/35101607;
RA Parkhill J., Dougan G., James K.D., Thomson N.R., Pickard D., Wain J.,
RA Churcher C., Mungall K.L., Bentley S.D., Holden M.T.G., Sebaihia M.,
RA Baker S., Basham D., Brooks K., Chillingworth T., Connerton P., Cronin A.,
RA Davis P., Davies R.M., Dowd L., White N., Farrar J., Feltwell T.,
RA Hamlin N., Haque A., Hien T.T., Holroyd S., Jagels K., Krogh A.,
RA Larsen T.S., Leather S., Moule S., O'Gaora P., Parry C., Quail M.,
RA Rutherford K., Simmonds M., Skelton J., Stevens K., Whitehead S.,
RA Barrell B.G.;
RT "Complete genome sequence of a multiple drug resistant Salmonella enterica
RT serovar Typhi CT18.";
RL Nature 413:848-852(2001).
RN [2] {ECO:0000313|EMBL:AAO71579.1, ECO:0000313|Proteomes:UP000002670}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700931 / Ty2 {ECO:0000313|Proteomes:UP000002670}, and Ty2
RC {ECO:0000313|EMBL:AAO71579.1};
RX PubMed=12644504; DOI=10.1128/JB.185.7.2330-2337.2003;
RA Deng W., Liou S.R., Plunkett G.III., Mayhew G.F., Rose D.J., Burland V.,
RA Kodoyianni V., Schwartz D.C., Blattner F.R.;
RT "Comparative genomics of Salmonella enterica serovar Typhi strains Ty2 and
RT CT18.";
RL J. Bacteriol. 185:2330-2337(2003).
RN [3] {ECO:0000313|EMBL:HAE0418666.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=09-1703 {ECO:0000313|EMBL:HAE3629351.1}, 12-0437
RC {ECO:0000313|EMBL:HAF7360073.1}, 13-0747
RC {ECO:0000313|EMBL:HAF0685916.1}, 13-7562
RC {ECO:0000313|EMBL:HAE9579043.1}, IP E.88.374
RC {ECO:0000313|EMBL:HAE7811777.1},
RC Sam_1c96eabc-5ba9-4785-8bb4-b62bc64a6574
RC {ECO:0000313|EMBL:HAE0418666.1}, and
RC Sam_2e1fd039-ec06-4964-b74e-443d7665d7a0
RC {ECO:0000313|EMBL:HAE0480808.1};
RX PubMed=30286803;
RA Souvorov A., Agarwala R., Lipman D.J.;
RT "SKESA: strategic k-mer extension for scrupulous assemblies.";
RL Genome Biol. 19:153-153(2018).
RN [4] {ECO:0000313|EMBL:EBW2554634.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=186520 {ECO:0000313|EMBL:EDG8894196.1}, 257355
RC {ECO:0000313|EMBL:EBW2554634.1}, 348081
RC {ECO:0000313|EMBL:EDI0994721.1}, 588927
RC {ECO:0000313|EMBL:EBS6527913.1}, and 643219
RC {ECO:0000313|EMBL:EBZ9856156.1};
RA Ashton P.M., Dallman T., Nair S., De Pinna E., Peters T., Grant K.;
RL Submitted (JUL-2018) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000313|EMBL:HAE0418666.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=09-1703 {ECO:0000313|EMBL:HAE3629351.1}, 12-0437
RC {ECO:0000313|EMBL:HAF7360073.1}, 13-0747
RC {ECO:0000313|EMBL:HAF0685916.1}, 13-7562
RC {ECO:0000313|EMBL:HAE9579043.1}, IP E.88.374
RC {ECO:0000313|EMBL:HAE7811777.1},
RC Sam_1c96eabc-5ba9-4785-8bb4-b62bc64a6574
RC {ECO:0000313|EMBL:HAE0418666.1}, and
RC Sam_2e1fd039-ec06-4964-b74e-443d7665d7a0
RC {ECO:0000313|EMBL:HAE0480808.1};
RG NCBI Pathogen Detection Project;
RL Submitted (JAN-2019) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000313|EMBL:QZA29227.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=ISP2825 {ECO:0000313|EMBL:QZA29227.1};
RA Lee G.Y., Song J.;
RT "Complete Genome Sequence of Salmonella enterica Serovar Typhi Strain
RT ISP2825.";
RL Submitted (AUG-2021) to the EMBL/GenBank/DDBJ databases.
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. {ECO:0000256|ARBA:ARBA00025552,
CC ECO:0000256|PIRNR:PIRNR000381}.
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 Evidence={ECO:0000256|ARBA:ARBA00001700,
CC ECO:0000256|PIRNR:PIRNR000381};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|ARBA:ARBA00001947,
CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00333};
CC -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000256|ARBA:ARBA00001956,
CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
CC {ECO:0000256|ARBA:ARBA00005178, ECO:0000256|PIRNR:PIRNR000381}.
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. {ECO:0000256|PIRNR:PIRNR000381}.
CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC family. {ECO:0000256|ARBA:ARBA00010398}.
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DR EMBL; AE014613; AAO71579.1; -; Genomic_DNA.
DR EMBL; AL513382; CAD09193.1; -; Genomic_DNA.
DR EMBL; AAGWES010000025; EBS6527913.1; -; Genomic_DNA.
DR EMBL; AAHHUX010000025; EBW2554634.1; -; Genomic_DNA.
DR EMBL; AAHSWZ010000020; EBZ9856156.1; -; Genomic_DNA.
DR EMBL; AAMFQZ010000024; EDG8894196.1; -; Genomic_DNA.
DR EMBL; AAMJVG010000021; EDI0994721.1; -; Genomic_DNA.
DR EMBL; DAAQQG010000024; HAE0418666.1; -; Genomic_DNA.
DR EMBL; DAAQQU010000005; HAE0480808.1; -; Genomic_DNA.
DR EMBL; DAARRK010000031; HAE3629351.1; -; Genomic_DNA.
DR EMBL; DAATAS010000024; HAE7811777.1; -; Genomic_DNA.
DR EMBL; DAATPQ010000006; HAE9579043.1; -; Genomic_DNA.
DR EMBL; DAATYW010000005; HAF0685916.1; -; Genomic_DNA.
DR EMBL; DAAWCE010000009; HAF7360073.1; -; Genomic_DNA.
DR EMBL; CP080960; QZA29227.1; -; Genomic_DNA.
DR RefSeq; NP_458507.1; NC_003198.1.
DR RefSeq; WP_000095965.1; NZ_QXGZ01000028.1.
DR AlphaFoldDB; Q8Z1V6; -.
DR STRING; 220341.gene:17588237; -.
DR KEGG; stt:t4115; -.
DR KEGG; sty:STY4405; -.
DR PATRIC; fig|220341.7.peg.4504; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_2_0_6; -.
DR OMA; ADCIAMS; -.
DR OrthoDB; 9803687at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000000541; Chromosome.
DR Proteomes; UP000002670; Chromosome.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
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 {ECO:0000256|ARBA:ARBA00022605,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Cobalamin {ECO:0000256|ARBA:ARBA00022628, ECO:0000256|PIRNR:PIRNR000381};
KW Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR000381}; Repeat {ECO:0000256|ARBA:ARBA00022737};
KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRNR:PIRNR000381}.
FT DOMAIN 5..325
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 356..617
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 650..744
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 746..881
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 897..1227
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 694
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 756..760
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
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:0000256|PIRSR:PIRSR000381-1"
FT BINDING 804
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 808
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 860
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 946
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1134
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1189..1190
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1227 AA; 136019 MW; 5A8080F777214A56 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 MSRAVAGLSP RQLPDIPVAC RLSGLEPLNI GDDSLFVNVG
ERTNVTGSAK FKRLIKEEKY SEALDVARQQ VESGAQIIDI NMDEGMLDAE AAMVRFLSLI
AGEPDIARVP IMIDSSKWEV IEKGLKCIQG KGIVNSISMK EGVEAFIHHA KLLRRYGAAV
VVMAFDEQGQ ADTRERKIEI CRRAYKILLE EVGFPPEDII FDPNIFAVAT GIEEHNNYAQ
DFIGACEDIK RELPHALISG GVSNVSFSFR GNDPVREAIH AVFLYYAIRN GMDMGIVNAG
QLAIYDNLPA ELRDAVEDVI LNRRDDGTER LLDLAEKYRG SKTDEAASAQ 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 FAVTGGLKED ALADAFEAQH
DDYNKIMVKA IADRLAEAFA EYLHERVRKV YWGYAPNESL SNDELIRENY QGIRPAPGYP
ACPEHTEKGT IWQLLDVEKH TGMKLTESFA MWPGASVSGW YFSHPESKYF AVAQIQRDQV
TDYAFRKGMS VEDVERWLAP NLGYDAD
//
