METH_CAEBR
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 03-AUG-2022, entry version 79.
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.CBG20636; -.
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; 731388at2759; -.
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: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; -; 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; 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
