ID METH_SYNY3 Reviewed; 1195 AA. AC Q55786; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 152. 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=slr0212; OS Synechocystis sp. (strain PCC 6803 / Kazusa). OC Bacteria; Cyanobacteriota; Cyanophyceae; Synechococcales; Merismopediaceae; OC Synechocystis. OX NCBI_TaxID=1111708; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 27184 / PCC 6803 / N-1; RX PubMed=8590279; DOI=10.1093/dnares/2.4.153; RA Kaneko T., Tanaka A., Sato S., Kotani H., Sazuka T., Miyajima N., RA Sugiura M., Tabata S.; RT "Sequence analysis of the genome of the unicellular cyanobacterium RT Synechocystis sp. strain PCC6803. I. Sequence features in the 1 Mb region RT from map positions 64% to 92% of the genome."; RL DNA Res. 2:153-166(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=PCC 6803 / Kazusa; RX PubMed=8905231; DOI=10.1093/dnares/3.3.109; RA Kaneko T., Sato S., Kotani H., Tanaka A., Asamizu E., Nakamura Y., RA Miyajima N., Hirosawa M., Sugiura M., Sasamoto S., Kimura T., Hosouchi T., RA Matsuno A., Muraki A., Nakazaki N., Naruo K., Okumura S., Shimpo S., RA Takeuchi C., Wada T., Watanabe A., Yamada M., Yasuda M., Tabata S.; RT "Sequence analysis of the genome of the unicellular cyanobacterium RT Synechocystis sp. strain PCC6803. II. Sequence determination of the entire RT genome and assignment of potential protein-coding regions."; RL DNA Res. 3:109-136(1996). 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; BA000022; BAA10438.1; -; Genomic_DNA. DR PIR; S76592; S76592. DR AlphaFoldDB; Q55786; -. DR SMR; Q55786; -. DR STRING; 1148.gene:10499939; -. DR PaxDb; 1148-1001700; -. DR EnsemblBacteria; BAA10438; BAA10438; BAA10438. DR KEGG; syn:slr0212; -. DR eggNOG; COG0646; Bacteria. DR eggNOG; COG1410; Bacteria. DR InParanoid; Q55786; -. DR PhylomeDB; Q55786; -. DR UniPathway; UPA00051; UER00081. DR Proteomes; UP000001425; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW. DR GO; GO:0008705; F:methionine synthase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0050667; P:homocysteine metabolic process; IBA:GO_Central. DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0046653; P:tetrahydrofolate metabolic process; IBA:GO_Central. 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; 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; 2. 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..1195 FT /note="Methionine synthase" FT /id="PRO_0000204537" FT DOMAIN 1..309 FT /note="Hcy-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT DOMAIN 340..599 FT /note="Pterin-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334" FT DOMAIN 629..722 FT /note="B12-binding N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667" FT DOMAIN 724..859 FT /note="B12-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666" FT DOMAIN 896..1195 FT /note="AdoMet activation" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346" FT BINDING 228 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 294 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 734..738 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 737 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 782 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 838 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 945 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 1138 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 1195 AA; 132540 MW; 1D9635B1B1DDB583 CRC64; MKSAFLDRIH SPDRPVLVFD GAMGTNLQVQ NLTAADFGGA EYEGCNEYLV HTKPEAVATV HRAFYEAGAD VVETDTFGGT PLVLAEYDLA DQSYYLNKAA AELAKAVAAE FSTPEKPRFV AGSMGPGTKL PTLGHVDYDS LKDAYVVQVR GLYDGGVDLL LVETCQDVLQ IKAALNAIEQ VFAEKGDRLP LMVSVTMETM GTMLVGTEMA AALAILEPYP IDILGLNCAT GPDLMKEHVK YLSEHSPFVV SCIPNAGLPE NVGGQAFYRL TPMELQMSLM HFIEDLGVQV IGGCCGTRPD HIKALADIAK DLQPKQRQPH YEPSAASIYS TQTYAQENSF LIIGERLNAS GSKKCRDLLN AEDWDSLVSL AKSQVKEGAQ ILDVNVDYVG RDGVRDMKEL ASRLVNNVTL PLMLDSTEWQ KMEAGLKVAG GKCILNSTNY EDGEERFYKV LEIAKEYGAG IVIGTIDEDG MGRTADKKFE IAKRAYEAAI AFGIPATEIF FDPLALPIST GIEEDRENGK ATVDAIRRIR QELPDCHILL GVSNVSFGLN PAARQVLNSI FLHECMQVGM DAAIVSANKI LPLAKIDPEQ QQVCLDLIYD RREFEGERCT YDPLTKLTTL FEGKTTKRDK SGDANLPVEE RLKRHIIDGE RLGLEEALNE ALKLYAPLDI INIYLLDGMK VVGELFGSGQ MQLPFVLQSA QTMKAAVAFL EPHMDKDDSA DNAKGTFLIA TVKGDVHDIG KNLVDIILSN NGYRVVNLGI KQPVENIIEA YKKHRPDCIA MSGLLVKSTA FMKENLEVFN QEGITVPVIL GGAALTPKFV HQDCQNTYKG QVIYGKDAFA DLHFMDKLMP AKNSHNWDDF QGFLGEYATE NGHNVTTDDG AKTNFGIEEE KLIDASEQSR EPEVIDTVRS EAVDPDLERP VPPFWGTKIL QSSDISLDEV FPLLDLQALF VGQWQFRKPR EQSREEYEQF LAEKVHPILA EWKGKVMAEN LLHPTVVYGY FPCQSQGNTL LIYDPELVSQ NNGQIPPDAT AIAKFEFPRQ KSGRRLCIAD FFASKESGIT DVFPLQAVTV GEIATEYARK LFAGDNYTDY LYFHGMAVQM AEALAEWTHQ RIRQELGFGH LDPDNIRDLL QQRYQGSRYS FGYPACPNMQ DQYTQLELLQ TERIGLYMDE SEQVYPEQST TAIISYHPAA KYFSA //