ID J9DJ06_9PROT Unreviewed; 1237 AA.
AC J9DJ06;
DT 31-OCT-2012, integrated into UniProtKB/TrEMBL.
DT 31-OCT-2012, sequence version 1.
DT 27-MAR-2024, entry version 62.
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 ORFNames=IMCC14465_03100 {ECO:0000313|EMBL:EJW21916.1};
OS alpha proteobacterium IMCC14465.
OC Bacteria; Pseudomonadota; Alphaproteobacteria; PS1 clade.
OX NCBI_TaxID=1220535 {ECO:0000313|EMBL:EJW21916.1, ECO:0000313|Proteomes:UP000004836};
RN [1] {ECO:0000313|EMBL:EJW21916.1, ECO:0000313|Proteomes:UP000004836}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IMCC14465 {ECO:0000313|EMBL:EJW21916.1,
RC ECO:0000313|Proteomes:UP000004836};
RX PubMed=23209213; DOI=10.1128/JB.01888-12;
RA Yang S.J., Kang I., Cho J.C.;
RT "Genome Sequence of Strain IMCC14465, Isolated from the East Sea, Belonging
RT to the PS1 Clade of Alphaproteobacteria.";
RL J. Bacteriol. 194:6952-6953(2012).
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 -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:EJW21916.1}.
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DR EMBL; ALYF01000002; EJW21916.1; -; Genomic_DNA.
DR AlphaFoldDB; J9DJ06; -.
DR STRING; 1220535.IMCC14465_03100; -.
DR PATRIC; fig|1220535.3.peg.307; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR OrthoDB; 9803687at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000004836; Unassembled WGS sequence.
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};
KW Reference proteome {ECO:0000313|Proteomes:UP000004836};
KW 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 9..329
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 360..621
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 652..746
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 757..893
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 909..1237
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 251
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 314
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 315
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 696
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 767..771
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 770
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 815
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 819
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 872
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 957
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1145
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1200..1201
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1237 AA; 135802 MW; 27A32464629F27CB CRC64;
MSWNREKRIA ELPRLTEQRI LTLDGAMGTM IQRHKPDEAT YRGSRFADFH VDLQGNNDLL
SLTQPDMIRD IHTAYLEAGA DILETNTFSS TTIAQADYEL ENFAYEMNVI GAKLAREACD
TFEAADPSRP RYVAGALGPT NRTASISPDV NDPGMRNVHY DELVEAYAAA TRGLIEGGAD
IIIVETVFDT LNAKAALHGV QSVFDETGIR LPLMVSGTIT DRSGRTLSGQ TTEAFWNSIK
HCKPFSVGLN CALGAEEMRP YVAEIARIAD TNICIYPNAG LPNEFGEYDQ MAAEMASIVG
EFAESGLVNI LGGCCGTTPD HIAAISTAAG QNNPRPIPEI DKRLRLSGLE PFTMTEDIRF
VNIGERTNVT GSAKFRKLIT DNDYEAALDV ARQQVENGAQ IIDVNMDEGM LDSEAAMTKF
LNLAATEPDI ARVPVMIDSS KWSVIEAGLK CVQGKAVVNS ISLKEGEAEF LEHARLCLRY
GAAVIVMAFD EQGQADTADR KFEICKRSYH LLVDEVGFPP EDIIFDPNIF AVATGIEEHN
NYAVDFIEAT KRIRQELPGA HVSGGVSNIS FSFRGNDAVR EAMHSAFLYH AIHSGMDMGI
VNAGQLAIYE DIDANLKSAV EDVLLNANDN ATDHLLKVAE GFLGQGGAKQ EADLSWREGS
VPERLMHALV NGIGDFIEED TELARQGFDR PLNVIEGPLM DGMNRVGDLF GDGKMFLPQV
VKSARVMKKA VAYLEPFMDK EKEEAQKAGA NIQSSSKGKV LMATVKGDVH DIGKNIVGVV
LQCNNFDVID MGVMVPANDI IDRAVEEQVD IIGLSGLITP SLDEMCHVAA EMERRGLNIP
LLIGGATTSK IHTAVKINPN YERGQTVYVT DASRAVGVAS RLLSEETSED YCKEIRSDYE
DMAEKHARGR SEDKRCPIEK ARANAFKGDD VTPVTPSFLG TKVFEDYNLA ELRDYIDWTP
FFQSWDLHGR YPAILSDNVV GEAATSLFKD ANDMLDKMIN EKWLTAKAVI GFWPAARDGD
DIIVYEDETR DAELARLHTL RQQMLRTNNR PNFALSDYIQ PVGGKPDYIG GFAVTSGHGE
DDVAKKFEAD GDDYSSIMSK ALADRLAEAF AERMHQRVRT ELWGYAPDEA LDNEALINEA
FTGIRPAAGY PAQPDHTEKG TLFELLDAEA AIGLTLTESF AMWPGAAVSG LYFSHPESAY
FGVGKINRDQ VADYAERKGM TLEICEKWMA PILSYKA
//
