ID A0A2Z5EDT2_9SPHN Unreviewed; 883 AA.
AC A0A2Z5EDT2;
DT 10-OCT-2018, integrated into UniProtKB/TrEMBL.
DT 10-OCT-2018, sequence version 1.
DT 27-MAR-2024, entry version 21.
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 Name=metH {ECO:0000313|EMBL:AXB77770.1};
GN ORFNames=TQ38_015700 {ECO:0000313|EMBL:AXB77770.1};
OS Novosphingobium sp. P6W.
OC Bacteria; Pseudomonadota; Alphaproteobacteria; Sphingomonadales;
OC Sphingomonadaceae; Novosphingobium.
OX NCBI_TaxID=1609758 {ECO:0000313|EMBL:AXB77770.1, ECO:0000313|Proteomes:UP000032296};
RN [1] {ECO:0000313|EMBL:AXB77770.1, ECO:0000313|Proteomes:UP000032296}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=P6W {ECO:0000313|EMBL:AXB77770.1,
RC ECO:0000313|Proteomes:UP000032296};
RA Nikolaichik Y.A., Safronova V.I., Belimov A., Gogolev Y.V., Gogoleva N.E.;
RT "Complete genome sequence of Novosphingobium sp. P6W.";
RL Submitted (JUN-2018) 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; CP030352; AXB77770.1; -; Genomic_DNA.
DR RefSeq; WP_043977072.1; NZ_CP030352.1.
DR AlphaFoldDB; A0A2Z5EDT2; -.
DR STRING; 1609758.TQ38_18765; -.
DR KEGG; nov:TQ38_015700; -.
DR OrthoDB; 9803687at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000032296; Chromosome 1.
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 19..279
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 317..415
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 418..553
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 568..883
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 365
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 428..432
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 431
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 476
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 480
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 532
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 617
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 794
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 849..850
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 883 AA; 96576 MW; CFDBA41570BE2338 CRC64;
MTSTTSAPAS TPRSSGARFV NIGERTNVTG SAKFKKLVMA GDYPAAVEVA RQQVENGAQV
IDVNMDEGLL DAIEAMTTYL NLIAAEPDIA RVPVMIDSSK WDVIEAGLKC VSGKPIVNSI
SMKEGEEPFL HYARKCMDYG AAVVVMAFDE TGQADTKARK IEICQRAYKL LTGIGFPPED
IIFDPNVFAV ATGIEEHDRY GLDFIEAVAE IRATCPHVHF SGGLSNLSFS FRGNETVRRA
MHSVFLYHAI PAGLDMAIVN AGQLDVYDQI DPALREACED VIMMRTPGVG ADGRTATERL
IDLAESYKGK DVVAEKAAEE WRSWDVVKRL EHALVRGIDA YVVEDTEECR AAIEVAGGRP
IEVIEGPLMG GMNVVGDLFG SGKMFLPQVV KSARVMKKAV AHLIPFIEAS KEPGAKAKGR
IIMATVKGDV HDIGKNIVGV VLQCNGYEVI DLGVMVPWSK ILEQAAEHDA DIIGLSGLIT
PSLDEMVTVA EEMQRSEMTI PLLIGGATTS KVHTALRIDP AYKGPVIHVL DASRAVGVAS
QLLSDTQAEG FVSSVSIDYE KVREARANKG QSDLLSLADA RANRFPTDFA LKAPAPVEPG
LHVFEEWDLA DLAETFDWTP FFRAWELAGN YPNILTDEVV GESATSLFAD AQAMLKKIID
EKWLTAKGVC AFWPVRADGD DVLLDDGTRL PMLRQQVKKS RGRANFCLSD FIDPAGDWLG
GFAVGIHGIE PHLARFQAAH DDYSDILLKA LADRFAEAFA ERLHAHVRTR LWGYAADEQF
TNEALIREEY RGIRPAPGYP ACPDHSLKPI LFDLLRAEDN AGIILTESQA MLPTAAVSGF
YFAHPESQYF GVARIGRDQL EDYAVRRDVD LPTAERWLRP NLD
//
