METH_ALIF1
ID METH_ALIF1 Reviewed; 1226 AA.
AC Q5E814;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
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=VF_0337;
OS Aliivibrio fischeri (strain ATCC 700601 / ES114) (Vibrio fischeri).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Aliivibrio.
OX NCBI_TaxID=312309;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700601 / ES114;
RX PubMed=15703294; DOI=10.1073/pnas.0409900102;
RA Ruby E.G., Urbanowski M., Campbell J., Dunn A., Faini M., Gunsalus R.,
RA Lostroh P., Lupp C., McCann J., Millikan D., Schaefer A., Stabb E.,
RA Stevens A., Visick K., Whistler C., Greenberg E.P.;
RT "Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with
RT pathogenic congeners.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:3004-3009(2005).
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; CP000020; AAW84832.1; -; Genomic_DNA.
DR RefSeq; WP_011261140.1; NC_006840.2.
DR RefSeq; YP_203720.1; NC_006840.2.
DR AlphaFoldDB; Q5E814; -.
DR SMR; Q5E814; -.
DR STRING; 312309.VF_0337; -.
DR EnsemblBacteria; AAW84832; AAW84832; VF_0337.
DR KEGG; vfi:VF_0337; -.
DR PATRIC; fig|312309.11.peg.328; -.
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; UP000000537; 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_0000204539"
FT DOMAIN 7..327
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 358..619
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 652..746
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 748..883
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 899..1226
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 249
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 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 696
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 758..762
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 761
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 806
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 810
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 862
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 949
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1137
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1192..1193
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1226 AA; 136369 MW; A1464CA5E141F3BD CRC64;
MAGSNIKVQI EKQLSERILL IDGGMGTMIQ GYKFEEEDYR GERFNKWHCD LKGNNDLLVL
SQPQIIRDIH EAYLEAGADI LETNTFNATT IAMADYDMES LSEEINFEAA KLAREVADKW
TEKTPNKPRY VAGVLGPTNR TCSISPDVND PGFRNVSFDE LVEAYSESTR ALIRGGSDLI
LIETIFDTLN AKACSFAVES VFEELDITLP VMISGTITDA SGRTLSGQTT EAFYNALRHV
KPISFGLNCA LGPDELREYV SDLSRISECY VSAHPNAGLP NAFGEYDLSP EDMAEHVAEW
ASSGFLNLIG GCCGTTPEHI RQMALVVEGV KPRQLPELPV ACRLSGLEPL TIEKDSLFIN
VGERTNVTGS ARFKRLIKEE LYDEALSVAQ EQVENGAQII DINMDEGMLD AEACMVRFLN
LCASEPEISK VPVMVDSSKW EVIEAGLKCI QGKGIVNSIS LKEGKEKFVH QAKLIRRYGA
AVIVMAFDEV GQADTRERKI EICTNAYNIL VDEVGFPPED IIFDPNIFAV ATGIDEHNNY
AVDFIEAVGD IKRTLPHAMI SGGVSNVSFS FRGNNYVREA IHAVFLYHCF KNGMDMGIVN
AGQLEIYDNV PEDLREAVED VVLNRRDDST ERLLDIATEY LERAVGKVED KSALEWRDWP
VEKRLEHSLV KGITEFIVED TEEARINAEK PIEVIEGPLM DGMNVVGDLF GEGKMFLPQV
VKSARVMKQA VAHLEPFINA SKEVGATNGK ILLATVKGDV HDIGKNIVGV VLQCNNYEII
DLGVMVSCET ILKVAKEENV DIIGLSGLIT PSLDEMVHVA KEMERQGFDL PLLIGGATTS
KAHTAVKIEQ NYSQPVVYVN NASRAVGVCT SLLSDELKPS FVEKLDIDYE RVREQHSRKQ
PRTKPVTLEV ARANKVAIDW ASYTPPVPLK PGVHIFDNFD VSTLRNYIDW TPFFMTWSLV
GKYPKILDHE EVGEEAKRLF KDANDLLDRV EKEGLLKARG MCALFPASSV GDDIEVYTDE
SRTKVAKVLH NLRQQTEKPK GFNYCLSDYI APKESGKNDW IGGFAVTGGI GERELADEYK
ANGDDYNAIM IQAVADRLAE AFAEYLHEKV RKEIWGYSPN ETLSNDDLIR EKYQGIRPAP
GYPACPEHTE KGALWELMNV EESIGMSLTS SYAMWPGASV SGMYFSHPDS RYFAIAQIQQ
DQAESYADRK GWNMLEAEKW LGPNLN
