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 27-MAR-2024, entry version 111. 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; Pseudomonadota; 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}. 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; 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 OrthoDB; 9803687at2; -. 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 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; 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 //