ID G2FIT3_9GAMM Unreviewed; 1234 AA. AC G2FIT3; DT 16-NOV-2011, integrated into UniProtKB/TrEMBL. DT 16-NOV-2011, sequence version 1. DT 12-OCT-2022, entry version 62. DE RecName: Full=Methionine synthase {ECO:0000256|ARBA:ARBA00013998, ECO:0000256|PIRNR:PIRNR000381}; DE EC=2.1.1.13 {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|PIRNR:PIRNR000381}; DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|ARBA:ARBA00031040, ECO:0000256|PIRNR:PIRNR000381}; GN Name=metH {ECO:0000313|EMBL:EGW53268.1}; GN ORFNames=TevJSym_bg00040 {ECO:0000313|EMBL:EGW53268.1}; OS endosymbiont of Tevnia jerichonana (vent Tica). OC Bacteria; Proteobacteria; Gammaproteobacteria; sulfur-oxidizing symbionts. OX NCBI_TaxID=1049564 {ECO:0000313|EMBL:EGW53268.1, ECO:0000313|Proteomes:UP000005167}; RN [1] {ECO:0000313|EMBL:EGW53268.1, ECO:0000313|Proteomes:UP000005167} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Gardebrecht A., Markert S., Felbeck H., Thuermer A., Albrecht D., RA Wollherr A., Kabisch J., Lehmann R., Daniel R., Liesegang H., Hecker M., RA Sievert S.M., Schweder T.; RT "The endosymbionts of the deep-sea tubeworms Riftia pachyptila and Tevnia RT jerichonana share an identical physiology as revealed by proteogenomic RT analyses."; RL ISME J. 0:0-0(2011). 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. {ECO:0000256|ARBA:ARBA00025552, CC ECO:0000256|PIRNR:PIRNR000381}. 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 Evidence={ECO:0000256|ARBA:ARBA00001700, CC ECO:0000256|PIRNR:PIRNR000381}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000256|ARBA:ARBA00001947, CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00333}; CC -!- COFACTOR: CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115; CC Evidence={ECO:0000256|ARBA:ARBA00001956, CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1}; CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1. CC {ECO:0000256|ARBA:ARBA00005178, ECO:0000256|PIRNR:PIRNR000381}. 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. {ECO:0000256|PIRNR:PIRNR000381}. CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase CC family. {ECO:0000256|ARBA:ARBA00010398}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:EGW53268.1}. 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; AFZB01000033; EGW53268.1; -; Genomic_DNA. DR STRING; 1049564.TevJSym_bg00040; -. DR EnsemblBacteria; EGW53268; EGW53268; TevJSym_bg00040. DR PATRIC; fig|1049564.3.peg.2817; -. DR eggNOG; COG0646; Bacteria. DR eggNOG; COG1410; Bacteria. DR UniPathway; UPA00051; UER00081. DR Proteomes; UP000005167; Unassembled WGS sequence. DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-UniRule. DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule. 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 {ECO:0000256|ARBA:ARBA00022605, KW ECO:0000256|PIRNR:PIRNR000381}; KW Cobalamin {ECO:0000256|ARBA:ARBA00022628, ECO:0000256|PIRNR:PIRNR000381}; KW Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|PIRNR:PIRNR000381}; KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167, KW ECO:0000256|PIRNR:PIRNR000381}; KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603, KW ECO:0000256|PIRNR:PIRNR000381}; KW Reference proteome {ECO:0000313|Proteomes:UP000005167}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691, KW ECO:0000256|PIRNR:PIRNR000381}; KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381}; KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRNR:PIRNR000381}. FT DOMAIN 5..323 FT /note="Hcy-binding" FT /evidence="ECO:0000259|PROSITE:PS50970" FT DOMAIN 354..615 FT /note="Pterin-binding" FT /evidence="ECO:0000259|PROSITE:PS50972" FT DOMAIN 647..741 FT /note="B12-binding N-terminal" FT /evidence="ECO:0000259|PROSITE:PS51337" FT DOMAIN 745..880 FT /note="B12-binding" FT /evidence="ECO:0000259|PROSITE:PS51332" FT DOMAIN 896..1232 FT /note="AdoMet activation" FT /evidence="ECO:0000259|PROSITE:PS50974" FT BINDING 245 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT BINDING 308 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT BINDING 309 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT BINDING 691 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 755..759 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 758 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:0000256|PIRSR:PIRSR000381-1" FT BINDING 803 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 807 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 859 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 946 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 1139 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 1194..1195 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" SQ SEQUENCE 1234 AA; 136285 MW; D5F649C9B4E4EA60 CRC64; MDNITPELES ILCERILILD GAMGTMIQRH KLTEEDYRGE RFTDWPSDLK GNNDLLVLSQ PELIRNIHEE YMEAGADILE TNTFGANRIS MADYDMQELA YEMNVAGARL CREAADKYAT PEKPRYVAGV LGPTNRTASI SPDVNDPGAR NISFDELVEA YAEATRGLIE GGVDILLIET IFDTLNAKAA VAACEQVFDQ DQLRLPIMIS GTITDASGRT LSGQTTEAFY NSLRHARPIS IGLNCALGPE LMRQYVEEIS RVAECYVNVH PNAGLPNEFG EYDLGPEAMG QQIAEWAEAG FLNIIGGCCG TTPAHIKAIA EAVADQAPRK LPEIRPECRL SGLEPLNIGP DSLFVNVGER ANVTGSAKFK RLILNEEYEE ALDVCRAQVE NGAQVVDVNM DEAMLDGVAA MQRFLNLCAG EPDISKVPVM IDSSKWEIIE AGLKCVQGKP IVNSISMKEG IDKFKQQAKL CRRYGAAVIV MAFDEEGQAD TQARKVEICT RAYQILTEEV GFPAEDIIFD PNIFAVATGI PEHDNYGVDF IEATREIKAA CPHALISGGV SNVSFSFRGN NPVREAIHAV FLYHAIQAGM DMGIVNAAQL AVYDDLPAEL RDAVEDVVLN KDPEAGDRLV EIAPNYAGDV VGGNKVEDLE WRSWPVNKRL EHALVKGITE YIDTDTEEAR LAVDKSLEVI EGPLMDGMNV VGDLFGAGKM FLPQVVKSAR VMKKSVAYLE PFLEAEKAEC GVQAQGKILM ATVKGDVHDI GKNIVGVVLQ CNNYEVIDIG VMVPADTILK QAQEHQVDII GLSGLITPSL DEMVHVAKEM KRLRMSQPLM IGGATTSIAH TAVKIEPEYD HPVVYVPDAS RAVGVASNLL SKDLRDDYIA DLRRSYEDVR ERRASKNEAR NLVPIEAARA NPVAIDWDNF VACEPNKLGV NVMDDIQLEL LIDYIDWTFF FHAWQLKGRY PQILEDREKG EEAKKLLADA REMLHKIITE KWLTAKAVIG LFPANAVGDD VEVYGLQPAA GEQRRPISTL HFLRKQGKQP KGKANTCLAD FIAPKASGHS DYIGGFACTA GIGINDKIVE FEKDHDDYSA IMLKALADRL AEALAEWLHE RVRRHYWGYA ANEKLSNEER VAEKYTGIRP AMGYPASPDH TEKDMLWELL DVEKNTGIWL TEAKAMVPTA AVSGLYFSHP DSHYFAVGKI NRDQVVSYAA RIDMELQEVE RWLAPNLAYE PESN //