ID A0A1C0Y5R2_9BACL Unreviewed; 1142 AA.
AC A0A1C0Y5R2;
DT 02-NOV-2016, integrated into UniProtKB/TrEMBL.
DT 02-NOV-2016, sequence version 1.
DT 27-MAR-2024, entry version 43.
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=A6M13_07230 {ECO:0000313|EMBL:OCS82474.1};
OS Caryophanon tenue.
OC Bacteria; Bacillota; Bacilli; Bacillales; Planococcaceae; Caryophanon.
OX NCBI_TaxID=33978 {ECO:0000313|EMBL:OCS82474.1, ECO:0000313|Proteomes:UP000093199};
RN [1] {ECO:0000313|EMBL:OCS82474.1, ECO:0000313|Proteomes:UP000093199}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 14152 {ECO:0000313|EMBL:OCS82474.1,
RC ECO:0000313|Proteomes:UP000093199};
RA Verma A., Pal Y., Krishnamurthi S.;
RT "Caryophanon tenue genome sequencing.";
RL Submitted (JUL-2016) 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:OCS82474.1}.
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DR EMBL; MASJ01000041; OCS82474.1; -; Genomic_DNA.
DR RefSeq; WP_066548454.1; NZ_MASJ01000041.1.
DR AlphaFoldDB; A0A1C0Y5R2; -.
DR STRING; 33978.A6M13_07230; -.
DR OrthoDB; 9803687at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000093199; 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 Gene3D; 3.40.50.280; Cobalamin-binding domain; 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:UP000093199};
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 3..305
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 336..596
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 617..711
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 712..847
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 852..1142
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 227
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 290
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 291
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 722..726
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 725
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 770
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 826
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1085
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1139..1140
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1142 AA; 126249 MW; EE24492B80DE9971 CRC64;
MTKHLIEQQL EKRILILDGA MGTMLQNENL TPEDFGGEEL DGCNENLLLT RPDVLEKIHR
QYLEAGTDII CTNTFGATPL VLNEYDLGHL ADEINTAGVE IARKAVDEFS TPEWPRFVAG
AMGPTTKTLS VTGGITFDEL VENFYVQARA LIKAGADLLL LETSQDMLNV KAGTLGVKQA
FDELGIELPV MISGTIEPMG TTLAGQTIDA FYISIEHIQP LSVGLNCATG PEFMTDHIRS
LSELATSYVS CYPNAGLPDE EGCYHETPDS LSKKLRGFAE KGWLNIIGGC CGTTPAHITA
IREAVDGFTP RKRPEKTHGH AVSGIEPLLY DDTMRPLFIG ERTNVIGSRK FKNLIIDGKF
EEAAEIARAQ VKSGAHVIDI CLANPDRDEL EDMKQFMQEV VKKVKVPLVI DSTDEKVIEE
SLKFSQGKAI INSINLEDGE ERFDAVMPLV KKYGAAVVVG TIDEVGMGVT REKKLEVAER
SYKLLTEKWG LAPEDIIFDP LVFPVGTGDE QYIGSAEETI EGIRLIKQKL PGVLTVLGVS
NVSFGLPPVG REVLNAVYLY HCTQAGLDYA IVNTEKLERY ASIPEQEIQL ANDLIFNTND
QTLAVFTDFY RDKKKEKTED DIPKTVPERL AYYILEGTKE GLIPDLDAAL EIYDTPLDVI
NGPLMAGMAE VGRLFNDNQL IVAEVLQSAG VMKAAVAHLE SFMEKDEESA GKGKMVLATV
KGDVHDIGKN LVDIIMSNNG YRVVDLGIKV TPAELIEAIR KEKPDIIGLS GLLVKSAQQM
VITAQDFKEA GIDVPIIVGG AALSRRFTET KIAPNYDGPV MYAKDAMAGL ETINRLVDDA
ERPALLQELK DAQEKRAESD AKRAERPVAI MERPVRTVTD AQVFVPKDLR RHITREYSVA
HLQPYVNMRT LIGHHLGLKG NLDELLKAND PRAVQLTELT KGYLQSELLK PSSIYRFFPA
QSDGNDVVIY DPENPGVEIE RFTFPRQQKA PFLCLADFLR SKESGEMDYV ALMVVTAGHG
VRAEATRLKE EGKFLESHAI QATALELAEG FAERIHQEIR DQWGFPDATD FTMRDRFAAK
YQGQRFSFGY PACPNLEDQA KLFKLIQPED IGVNLTEGFM MEPEASVTAI VFAHPDARYF
NV
//
