METH_VIBVY
ID METH_VIBVY Reviewed; 1226 AA.
AC Q7MHB1;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Methionine synthase;
DE EC=2.1.1.13;
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase;
DE AltName: Full=Methionine synthase, vitamin-B12 dependent;
DE Short=MS;
GN Name=metH; OrderedLocusNames=VV2960;
OS Vibrio vulnificus (strain YJ016).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=196600;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=YJ016;
RX PubMed=14656965; DOI=10.1101/gr.1295503;
RA Chen C.-Y., Wu K.-M., Chang Y.-C., Chang C.-H., Tsai H.-C., Liao T.-L.,
RA Liu Y.-M., Chen H.-J., Shen A.B.-T., Li J.-C., Su T.-L., Shao C.-P.,
RA Lee C.-T., Hor L.-I., Tsai S.-F.;
RT "Comparative genome analysis of Vibrio vulnificus, a marine pathogen.";
RL Genome Res. 13:2577-2587(2003).
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 (By similarity). {ECO:0000250}.
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 -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
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 (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: L-homocysteine is bound via the zinc atom.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC family. {ECO:0000305}.
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DR EMBL; BA000037; BAC95724.1; -; Genomic_DNA.
DR RefSeq; WP_011151258.1; NC_005139.1.
DR AlphaFoldDB; Q7MHB1; -.
DR SMR; Q7MHB1; -.
DR STRING; 672.VV93_v1c26820; -.
DR PRIDE; Q7MHB1; -.
DR EnsemblBacteria; BAC95724; BAC95724; BAC95724.
DR KEGG; vvy:VV2960; -.
DR PATRIC; fig|196600.6.peg.2940; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_2_2_6; -.
DR OMA; ADCIAMS; -.
DR OrthoDB; 118138at2; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000002675; Chromosome I.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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; 1.10.1240.10; -; 1.
DR Gene3D; 3.10.196.10; -; 1.
DR Gene3D; 3.20.20.20; -; 1.
DR Gene3D; 3.20.20.330; -; 1.
DR InterPro; IPR003759; Cbl-bd_cap.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR011005; Dihydropteroate_synth-like.
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 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; SSF47644; SSF47644; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR SUPFAM; SSF56507; SSF56507; 1.
DR SUPFAM; SSF82282; SSF82282; 1.
DR TIGRFAMs; TIGR02082; metH; 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; Cobalamin; Cobalt; Metal-binding;
KW Methionine biosynthesis; Methyltransferase; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..1226
FT /note="Methionine synthase"
FT /id="PRO_0000204543"
FT DOMAIN 6..326
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 357..618
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 651..745
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 747..882
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 898..1226
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 695
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 757..761
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 760
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:0000250|UniProtKB:P13009"
FT BINDING 805
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 809
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 861
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 948
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1136
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1191..1192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1226 AA; 136333 MW; 299B647CC6D24028 CRC64;
MGSNIRAQIE AQLKQRILLI DGGMGTMIQG YKLQEQDYRG ERFADWHSDL KGNNDLLVLT
QPQLIKEIHH AYLEAGADIL ETNTFNATTI AMADYDMESL SEEINFAAAK LAREAADEWT
AKNPAKPRYV AGVLGPTNRT CSISPDVNDP GYRNVSFDEL VEAYSESTRA LIRGGSDLIL
IETIFDTLNA KACAFAVESV FEELGFALPV MISGTITDAS GRTLSGQTTE AFYNSLRHVR
PISFGLNCAL GPDELRPYVE ELSRISETFV STHPNAGLPN AFGEYDLSPE EMAEHVKEWA
QSGFLNLIGG CCGTTPEHIR HMAMAVEGES PRVLPEIPVA CRLSGLEPLT IAKDTLFVNV
GERTNVTGSA RFKRLIKEEL YDEALDVARE QVENGAQIID INMDEGMLDA EACMVRFLNL
CASEPEISKV PIMVDSSKWE VIEAGLKCIQ GKGIVNSISL KEGKEKFVEQ AKLIRRYGAA
VIVMAFDEVG QADTRERKLE ICTKAYRILV DEVGFPPEDV IFDPNIFAVA TGIDEHNNYA
VDFIEAVADI KRDLPHAMIS GGVSNVSFSF RGNNYVREAI HAVFLYHCFK NGMDMGIVNA
GQLEIYDNVP EKLREAVEDV VLNRRDDATE RLLEIAEEYR ENAVGKQEDA SALEWRTWSV
EKRLEHALVK GITEFIVEDT EEARLNASKP LEVIEGPLMD GMNVVGDLFG EGKMFLPQVV
KSARVMKQAV AHLEPFINAS KQVGSSNGKI LLATVKGDVH DIGKNIVGVV LQCNNYEIID
LGVMVPCEQI LKVAKEQQVD IIGLSGLITP SLDEMVHVAK EMERLGFDLP LLIGGATTSK
AHTAVKIEQN YSHPVVYVNN ASRAVGVCTS LLSDELRPAF VERLQADYEL VRDQHNRKKP
RTKPVTLEAA RANKVAIDWQ SYTPPAPSQP GVHVFDDFDV ATLRQYIDWT PFFLTWSLVG
KYPTIFEHEE VGEEAKRLFE DANEWLDRIE QEGLLKARGM CGLFPAASVG DDIEVYTDES
RTQVAKVLHN LRQQTEKPKG ANYCLSDYVA PKESGKKDWI GAFAVTGGVN ERELADQFKA
QGDDYNAIMI QAVADRLAEA FAEYLHERVR KEIWGYAADE NLSNEELIRE KYQGIRPAPG
YPACPEHTEK GPLWELLNVE ETIGMSLTSS YAMWPGASVS GWYFSHPDSR YFAIAQIQQD
QVESYAKRKG WDLLEAEKWL GPNING
