ID D5X700_THIK1 Unreviewed; 910 AA.
AC D5X700;
DT 13-JUL-2010, integrated into UniProtKB/TrEMBL.
DT 13-JUL-2010, sequence version 1.
DT 27-MAR-2024, entry version 73.
DE RecName: Full=Methionine synthase {ECO:0000256|PIRNR:PIRNR000381};
DE EC=2.1.1.13 {ECO:0000256|PIRNR:PIRNR000381};
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|PIRNR:PIRNR000381};
GN OrderedLocusNames=Tint_2807 {ECO:0000313|EMBL:ADG32147.1};
OS Thiomonas intermedia (strain K12) (Thiobacillus intermedius).
OC Bacteria; Pseudomonadota; Betaproteobacteria; Burkholderiales; Thiomonas.
OX NCBI_TaxID=75379 {ECO:0000313|EMBL:ADG32147.1};
RN [1] {ECO:0000313|EMBL:ADG32147.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 {ECO:0000313|EMBL:ADG32147.1};
RG US DOE Joint Genome Institute;
RA Lucas S., Copeland A., Lapidus A., Cheng J.-F., Bruce D., Goodwin L.,
RA Pitluck S., Davenport K., Detter J.C., Han C., Tapia R., Land M.,
RA Hauser L., Kyrpides N., Ovchinnikova G., Kerfeld C.A., Cannon G.C.,
RA Heinhorst S., Woyke T.;
RT "Complete sequence of Thiomonas intermedia K12.";
RL Submitted (APR-2010) 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|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|PIRNR:PIRNR000381};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|PIRNR:PIRNR000381};
CC -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000256|PIRNR:PIRNR000381,
CC 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|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; CP002021; ADG32147.1; -; Genomic_DNA.
DR AlphaFoldDB; D5X700; -.
DR STRING; 75379.Tint_2807; -.
DR KEGG; tin:Tint_2807; -.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_2_0_4; -.
DR BioCyc; TINT75379:TINT_RS14045-MONOMER; -.
DR UniPathway; UPA00051; UER00081.
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; 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; 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 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; 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; PS50972; PTERIN_BINDING; 1.
PE 3: Inferred from homology;
KW Amino-acid biosynthesis {ECO:0000256|PIRNR:PIRNR000381};
KW Cobalamin {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1};
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|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|PIRNR:PIRNR000381,
KW ECO:0000256|PIRSR:PIRSR000381-2};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381};
KW Zinc {ECO:0000256|PIRNR:PIRNR000381}.
FT DOMAIN 27..288
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 318..416
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 425..564
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 578..910
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 366
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 435..439
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 438
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 483
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 487
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 543
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 628
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 821
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 875..876
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 910 AA; 99997 MW; AB97F2C1B0EE38DE CRC64;
MSQDAPALPP LQLSGLEPLI VGPGSLFVNI GERTNVTGSK AFARMILAGE YDKALAVARQ
QVENGAQIID VNMDEAMLDS KAAMVRFLNL MASEPDIARV PVMIDSSKWS VIEAGLRCVQ
GKAVVNSISM KEGEAEFIRQ ARLLRRYGAA TVVMAFDEQG QADTFERKTQ ICERAYRLLV
DQVGFPAEDI IFDPNIFAIA TGIEEHNNYA VDFINATRWI KQNLPGAKVS GGVSNVSFSF
RGNEPVREAI HTVFLYHAIA AGMDMGIVNA GQMGVYDDLD PELRERVEDV VLNRRPDATE
RLLEVAEAVK GAAKDDSVRL AWRELPVRQR LSHALVHGIT DFIVDDTEEV WQTIRAEGGR
PLHVIEGPLM DGMNVVGDLF GAGKMFLPQV VKSARVMKQA VAHLLPYIEA EKLEMQAAGC
DVRAKGKIVI ATVKGDVHDI GKNIVTVVLQ CNNFEVVNMG VMVPAKDILA KAREEGADII
GLSGLITPSL EEMQHVAAEM QRDDYFRSRK MPLLIGGATT SRVHTAVKIS PHYEGPVVYV
PDASRSVGVA QSLLSDQAAA YIAEIEADYE KVRILHANKR VTPLVPLAAA RANKTKIDWS
GYTPPVPKFI GRRVFRNYDL SEIAACIDWA PFFQTWDLAG KFPDILTDDI VGESARRVYS
DAQRMLKRLI EGRWLTANAV IGLWPANSVN DDDIALYTDE SRSAELMVWH GLRQQTERPV
VDGVPRPNRA LADFIAPKGV AADYIGMFAV TAGLGVEAKE KAFLADLDDY SAIMLKSLAD
RLAEALAERM HQRVRTEFWA YAPEESLSNA ELIAEKYRGI RPAPGYPACP EHSVKGEMFA
ALQAQDIGMS LTESWAMMPA ASVSGFYFAH PQAQYFNVGA VGEDQKADWE RRAGRPLESV
AIQALEPAKV
//
