ID   METH_CAEBR              Reviewed;        1273 AA.
AC   A8XY95;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 2.
DT   27-MAR-2024, entry version 85.
DE   RecName: Full=Probable methionine synthase;
DE            EC=2.1.1.13;
DE   AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase;
DE   AltName: Full=Vitamin-B12 dependent methionine synthase;
DE            Short=MS;
GN   Name=metr-1; ORFNames=CBG20636;
OS   Caenorhabditis briggsae.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6238;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AF16;
RX   PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA   Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA   Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA   Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA   Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA   Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA   Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA   Durbin R.M., Waterston R.H.;
RT   "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT   genomics.";
RL   PLoS Biol. 1:166-192(2003).
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; HE600991; CAP37612.2; -; Genomic_DNA.
DR   AlphaFoldDB; A8XY95; -.
DR   SMR; A8XY95; -.
DR   STRING; 6238.A8XY95; -.
DR   WormBase; CBG20636; CBP04996; WBGene00039583; Cbr-metr-1.
DR   eggNOG; KOG1579; Eukaryota.
DR   HOGENOM; CLU_004914_2_0_1; -.
DR   InParanoid; A8XY95; -.
DR   OMA; ADCIAMS; -.
DR   OrthoDB; 66796at2759; -.
DR   UniPathway; UPA00051; UER00081.
DR   Proteomes; UP000008549; Chromosome II.
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; 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..1273
FT                   /note="Probable methionine synthase"
FT                   /id="PRO_0000412913"
FT   DOMAIN          7..327
FT                   /note="Hcy-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT   DOMAIN          360..621
FT                   /note="Pterin-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT   DOMAIN          652..749
FT                   /note="B12-binding N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT   DOMAIN          762..897
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT   DOMAIN          927..1273
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         699
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         772..776
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         775
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         820
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         824
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         876
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000250|UniProtKB:P13009"
FT   BINDING         977
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         1171
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         1225..1226
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1273 AA;  141762 MW;  7178233645CE06AE CRC64;
     MTRSSLFKEL ADIAKERIMI IDGAMGTMIQ REYMEEHDFR GEILKDHDKP LKGNNDLLSI
     TRPDIIYKIH KLYLEAGADF IETNTFSGTT IAQADYHCEH LVHEINYQSA LVARRACDDV
     GAATGIRRYV CGAIGPTNRT LSISPSVEKP DFRNVTFQEL VKAYGDQARS LIQGGVDVLL
     VETVFDSANA KAALFAIRTL FEDEGVPEIP VFLSGTIVDM SGRTLSGQTG EAFLVSTKQG
     KPIAVGLNCA LGAKDMRQFV QNMSLWSDTL ILCYPNAGLP NALGGYDETP EEMAEVLREF
     AQDGLVNIIG GCCGTTPDHI NAMYKAVQGI SPRVPPADPH AGKMLLSGLE PSIVGPETNF
     VNIGERCNVA GSRRFCNLIK NENYDTAIDV ARVQVDSGAQ ILDVNMDDGL LDGPYAMSKF
     LRLISSEPDV AKIPVCIDSS DFDVIIAGLE STQGKCVVNS ISLKEGEEKF KERARIVKRY
     GAAVVVMAFD EEGQAAETER KFEICERSYR ILTEEVGFNP NDIIFDANIL TIATGMDEHA
     NYGMYFIEAT RMIRENLPGA HVSGGVSNIS FSFRGMEAIR EAMHSVFLFY AIKAGMDMGI
     VNAGALPVYE DIDKPLLQLL EDLLFNRDPE ATEKLLVAAQ EMKKDGKKAD TKTDEWRNTS
     VEERLKFALV KGIDQFVVAD TEEARQNTEK YPRPLNVIER PLMDGMAVVG ELFGAGKMFL
     PQVIKSARVM KKAVAHLLPF MDAERQANIE KMGLDEDESP YQGTVVIATV KGDVHDIGKN
     IVAVVLGCNN FKVVDLGVMT PCENIIKAAI EEKADFIGLS GLITPSLDEM VHVAKEMNRV
     GLKIPLLIGG ATTSKTHTAV KIAPRYPHPV VHCLDASKSV VVCSSLSDMT VRDAFLQDLN
     EDYEDVRTKM CLVSYLNHFF ITEHYESLKD RRFVALGKTR EKKFNIDWNK FSPVKPSFIG
     RREFQNFDFK ELIPYIDWKP FFDVWQLRGK YPNRSYPKIF DDADVGGEAK RVFDDAQTWL
     KKLIDEKVLT ANAVVSFLPA ASEGDDIHVY DPETGNKLDT FYGLRQQSGR EHDQSHFCLS
     DFIRPLKIGV PDDYLGLFAC TAGLGAEEYC KVLEENHDDY ASIMVKALAD RLAEAYAEYL
     HKEVRVNLWG YSTNEQLTET DLLSIKYEGI RPACGYPSQP DHTEKRTLWK LLEAEKNGIV
     LTEHLAMLPA ASVSGLYFAN PQSQYFAVGK IDEDQVAFIY VRSKNVTDYA ARKNVPKEEV
     ERWLSPIIGY ELD
//