ID K6H5A9_9LEPT Unreviewed; 1247 AA.
AC K6H5A9;
DT 09-JAN-2013, integrated into UniProtKB/TrEMBL.
DT 09-JAN-2013, 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 Name=metH {ECO:0000313|EMBL:EKO76278.1};
GN ORFNames=LEP1GSC068_0310 {ECO:0000313|EMBL:EKO76278.1};
OS Leptospira sp. Fiocruz LV3954.
OC Bacteria; Spirochaetota; Spirochaetia; Leptospirales; Leptospiraceae;
OC Leptospira.
OX NCBI_TaxID=1193012 {ECO:0000313|EMBL:EKO76278.1, ECO:0000313|Proteomes:UP000002809};
RN [1] {ECO:0000313|EMBL:EKO76278.1, ECO:0000313|Proteomes:UP000002809}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Fiocruz LV3954 {ECO:0000313|EMBL:EKO76278.1,
RC ECO:0000313|Proteomes:UP000002809};
RA Harkins D.M., Durkin A.S., Brinkac L.M., Selengut J.D., Sanka R., DePew J.,
RA Ko A.I., Reis M.G., Ribeiro G.S., Wunder E.Jr., Vinetz J.M., Sutton G.G.,
RA Nelson W.C., Fouts D.E.;
RL Submitted (OCT-2012) 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}.
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:EKO76278.1}.
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; AKWV02000091; EKO76278.1; -; Genomic_DNA.
DR RefSeq; WP_008400451.1; NZ_AKWV02000091.1.
DR AlphaFoldDB; K6H5A9; -.
DR PATRIC; fig|1193012.3.peg.4366; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000002809; 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}; 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 13..333
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 364..629
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 657..751
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 756..891
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 907..1241
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 255
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 318
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 319
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 701
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 766..770
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 769
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 814
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 818
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 870
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 958
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1148
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1203..1204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1247 AA; 138414 MW; ADAC3468FB3E9DC2 CRC64;
MTYKVQNYTN PKAKELLSLL EKQILVIDGA MGTMIQRFPL TEDDFRGEVL KNHPHPLKGN
NELLCLTRPD VIEAIHVKFL EAGANILETN TFSSNQVSQG DYKTEFLVAD LNKAAVVCAR
NAIKKFQKTN RHQPCFLAGA IGPTTRTATL SPDVNNPAFR AVTFDDLVAT FYEQARALVE
AGVDLLLPET NIDTLNLKAA IFAIEQVFED LQVRIPVCLS VTITDASGRT LSGQTVEAFY
NSIAHCNPLS VGINCALGAD EMRPYIEELA RVSSCYISCY PNAGLPNAFG GYDQTPEEFG
KYIQEFASSG WLNIAGGCCG TTPEHIEAAA KAVRGKKPRV LPKIEEITRL SGLEPLNVTP
DKGFLLVGER TNVTGSPKFK KLIIEGNFEE AVSVALQQVE AGANIVDINF DEALLDGEAS
MRHFLNLVAG EPDIAKVPFM IDSSKWSVLE EGLKCIQGKP IVNSISLKEG EEKFLEHAKK
IRRYGAAAIV MAFDEQGQAA TKDDKVRICK RAYDLLVTKA NFSPTDIIFD PNILTVATGI
EEHNNYAVDF IEAVREIKKL CLGAKVSGGL SNVSFSFRGN NPVREAMHSV FLYYAIQAGM
DMAIVNAGML AVYEEIPKDL LGYVEDVILN RRPDATERLV EFAESVKSSG DKSEKKEEAW
REGTSVEERL SHALVKGIVE YIDQDTEEAR LKYGRPLTVI EGPLMDGMKI VGELFGAGKM
FLPQVVKSAR VMKKSVAYLL PFMEEEKKQS EQTSARPKFL IATVKGDVHD IGKNIVGVVL
ACNNYEVIDL GVMVPSDRIL EEAKKHNASI IGLSGLITPS LDEMVHVASE MKRTGFEIPL
LIGGATTSSA HTAVKIAPVY DQPVVHVVDA SRVVNVVNQL LHPDLNEAYS QKIKEDQKAA
RENYFNTRAE RKLISLEQAR NNREEIDWAT TRIDSPSLTG IRVFDEEVSL ETLIPFIDWT
PFFTAWELKG RYPAILESAT TGKQARELFA DAQKLMKTIV DGKLFKTKGV IGIFPANSVG
DDIEVYEDES RSRLLAVFHT LRQQIQKEDA TEPNYCLADY IAPKNSGRVD YIGGFAVTAG
HGVEEFAKEF ENNQDDYNSI MAKALGDRFA EAFAEYMHYK VRKEYWGYDK DESLSPEDLI
RERYRGIRPA AGYPASPDHT EKRILFDLLQ AEENTGITLT EHFAMWPASS VSGLYFAHPK
SKYFAVAKIN RDQIEEYANR KGMNVEEAER WLAPNLAYDP LAISAIR
//
