METH_SYNY3
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 03-AUG-2022, entry version 144.
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; Cyanobacteria; Synechococcales; Merismopediaceae; Synechocystis;
OC unclassified 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}.
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DR EMBL; BA000022; BAA10438.1; -; Genomic_DNA.
DR PIR; S76592; S76592.
DR AlphaFoldDB; Q55786; -.
DR SMR; Q55786; -.
DR STRING; 1148.1001700; -.
DR PaxDb; Q55786; -.
DR PRIDE; Q55786; -.
DR EnsemblBacteria; BAA10438; BAA10438; BAA10438.
DR KEGG; syn:slr0212; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR InParanoid; Q55786; -.
DR OMA; ADCIAMS; -.
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:0009086; P:methionine biosynthetic process; IBA:GO_Central.
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; -; 2.
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..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
