ID D3SCH9_THISK Unreviewed; 1263 AA.
AC D3SCH9;
DT 20-APR-2010, integrated into UniProtKB/TrEMBL.
DT 20-APR-2010, sequence version 1.
DT 24-JAN-2024, entry version 94.
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 OrderedLocusNames=TK90_0182 {ECO:0000313|EMBL:ADC70698.1};
OS Thioalkalivibrio sp. (strain K90mix).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Chromatiales;
OC Ectothiorhodospiraceae; Thioalkalivibrio.
OX NCBI_TaxID=396595 {ECO:0000313|EMBL:ADC70698.1, ECO:0000313|Proteomes:UP000009099};
RN [1] {ECO:0000313|Proteomes:UP000009099}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K90mix {ECO:0000313|Proteomes:UP000009099};
RG US DOE Joint Genome Institute;
RA Lucas S., Copeland A., Lapidus A., Cheng J.-F., Bruce D., Goodwin L.,
RA Pitluck S., Foster B., Sun H., Larimer F., Land M., Hauser L., Kyrpides N.,
RA Ivanova N., Sorokin D.Y., Muyzer G., Woyke T.;
RT "Complete sequence of chromosome of Thioalkalivibrio sp. K90mix.";
RL Submitted (FEB-2010) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EMBL:ADC70698.1, ECO:0000313|Proteomes:UP000009099}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K90mix {ECO:0000313|EMBL:ADC70698.1,
RC ECO:0000313|Proteomes:UP000009099};
RX PubMed=22675584; DOI=10.4056/sigs.2315092;
RA Muyzer G., Sorokin D.Y., Mavromatis K., Lapidus A., Foster B., Sun H.,
RA Ivanova N., Pati A., D'haeseleer P., Woyke T., Kyrpides N.C.;
RT "Complete genome sequence of Thioalkalivibrio sp. K90mix.";
RL Stand. Genomic Sci. 5:341-355(2011).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP001905; ADC70698.1; -; Genomic_DNA.
DR RefSeq; WP_012981597.1; NC_013889.1.
DR AlphaFoldDB; D3SCH9; -.
DR STRING; 396595.TK90_0182; -.
DR KEGG; tkm:TK90_0182; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_4_0_6; -.
DR OMA; ADCIAMS; -.
DR OrthoDB; 9803687at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000009099; 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.
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 648..742
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 744..879
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 895..1247
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 692
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 754..758
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 757
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 802
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 806
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 858
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 964
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1209..1210
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1263 AA; 140733 MW; 43BDBF5409C2DCCE CRC64;
MTATRNDIEK ALKERILILD GGMGTTIQLY KLEEADYRGE RFKDWESDLK GNNDLLSLTR
PDIIEQIHND YLEAGADIIE ANTFNGTRIA MADYHMEDLV PELNRESAKL ARKAADAWTE
KTPDKPRYVA GILGPTNRTA SISPDVNDPG ARNVDFDTLV ESYKEAAEAL VEGGVDILLI
ETVFDTLNAK AAIFAVKTLE DELGKELPIM ISGTITDASG RTLSGQTTEA FWNSVRHANP
VSIGLNCALG AKEMRQYVEE LSRIADTHVS AHPNAGLPNE FGDYDESPEQ MAADVGPWAE
QGLLNIIGGC CGTLPEHIRA MREAVEKFPP RKVPEIAPAC RLSGLEPCNI TDDSLFVNVG
ERTNVTGSRK FLRLIQNEEY DVALEVALNQ VEGGAQIIDI NMDEGMLESQ DAMVRFLNLL
AGEPDIARVP VMIDSSKFEI IEAGLKCVQG KAVVNSISMK EGEENFIKQA QLCRRYGAAI
VVMAFDEDGQ ADNEDRRVEI CTRAYRLLTE KVGFPAEDII FDPNIFAVAT GIEEHNNYGV
DFIEATRRIK QDLPHALVSG GVSNVSFSFR GNEPVREAIH AVFLYHAIKA GMDMGIVNAG
QLAVYDDIDE KLKEAVEDVV LNRRDDATER LLDLSEEYKG QGGGKKEENL EWREWEVTKR
LEHSLVKGID TYVVEDTEEA RQQYDRPIQV IEGPLMDGMN VVGDLFGEGK MFLPQVVKSA
RVMKKAVAHL IPYIEAEKTG TENNGKILMA TVKGDVHDIG KNIVGVVLQC NNFEVIDIGV
MQPGAEILKA AKEHDVDVIG LSGLITPSLE EMANFAADLE REGMTTPLMI GGATTSRAHT
AVKIEPNYSG PVVWVKDASR AVGVAQSLIS PELRENYAAE IREEYEKLRV QNAGRKKKTQ
WVTLEKARAN KPQIDWSSYT PTKPKALETD KLPGEPKVLH PHGDGSVLLR FDDFDLNEVR
NFIDWTPFFH SWQLHAAYPR ILDDEKVGEE ARKLFKDGQE MLDRMIEEKW VTLRGVVGFF
PANTVNDDDI EVYTDESRSK VLKKLHHLRQ QTEKRRGQPS HSLADFLMPK EAGGPDYLGA
FAVSAGGDVD AKAEEYEKAN DDYHAILVKS LADRLAEAFA ECMHQYVRKH YWGYVPDEAL
ENEDLIDEKY QGIRPAPGYP ACPEHTEKGT LWELLQADEH ADMTLTESYA MLPVSAVSGW
YFAHPESRYF GLGKVNRDQV EDYAKRKGMS FEEAERWLAP NIGYDDSDEA KAEARAEREA
RSA
//