ID   D0LDR3_GORB4            Unreviewed;      1199 AA.
AC   D0LDR3;
DT   15-DEC-2009, integrated into UniProtKB/TrEMBL.
DT   15-DEC-2009, sequence version 1.
DT   02-SEP-2026, entry version 104.
DE   RecName: Full=Methionine synthase {ECO:0000256|ARBA:ARBA00013998, ECO:0000256|NCBIfam:TIGR02082};
DE            EC=2.1.1.13 {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|NCBIfam:TIGR02082};
DE   AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|PIRNR:PIRNR000381};
GN   OrderedLocusNames=Gbro_2445 {ECO:0000313|EMBL:ACY21686.1};
OS   Gordonia bronchialis (strain ATCC 25592 / DSM 43247 / BCRC 13721 / JCM 3198
OS   / KCTC 3076 / NBRC 16047 / NCTC 10667) (Rhodococcus bronchialis).
OC   Bacteria; Bacillati; Actinomycetota; Actinomycetes; Mycobacteriales;
OC   Gordoniaceae; Gordonia.
OX   NCBI_TaxID=526226 {ECO:0000313|EMBL:ACY21686.1, ECO:0000313|Proteomes:UP000001219};
RN   [1] {ECO:0000313|Proteomes:UP000001219}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25592 / DSM 43247 / BCRC 13721 / JCM 3198 / KCTC 3076 /
RC   NBRC 16047 / NCTC 10667 {ECO:0000313|Proteomes:UP000001219};
RG   US DOE Joint Genome Institute (JGI-PGF);
RA   Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Dalin E., Tice H.,
RA   Bruce D., Goodwin L., Pitluck S., Kyrpides N., Mavromatis K., Ivanova N.,
RA   Ovchinnikova G., Saunders E., Brettin T., Detter J.C., Han C., Larimer F.,
RA   Land M., Hauser L., Markowitz V., Cheng J.-F., Hugenholtz P., Woyke T.,
RA   Wu D., Jando M., Schneider S., Goeker M., Klenk H.-P., Eisen J.A.;
RT   "The complete chromosome of Gordonia bronchialis DSM 43247.";
RL   Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|EMBL:ACY21686.1, ECO:0000313|Proteomes:UP000001219}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25592 / DSM 43247 / BCRC 13721 / JCM 3198 / KCTC 3076 /
RC   NBRC 16047 / NCTC 10667 {ECO:0000313|Proteomes:UP000001219};
RX   PubMed=21304674;
RA   Ivanova N., Sikorski J., Jando M., Lapidus A., Nolan M., Lucas S.,
RA   Del Rio T.G., Tice H., Copeland A., Cheng J.F., Chen F., Bruce D.,
RA   Goodwin L., Pitluck S., Mavromatis K., Ovchinnikova G., Pati A., Chen A.,
RA   Palaniappan K., Land M., Hauser L., Chang Y.J., Jeffries C.D., Chain P.,
RA   Saunders E., Han C., Detter J.C., Brettin T., Rohde M., Goker M.,
RA   Bristow J., Eisen J.A., Markowitz V., Hugenholtz P., Klenk H.P.,
RA   Kyrpides N.C.;
RT   "Complete genome sequence of Gordonia bronchialis type strain (3410).";
RL   Stand. Genomic Sci. 2:19-28(2010).
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}.
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DR   EMBL; CP001802; ACY21686.1; -; Genomic_DNA.
DR   RefSeq; WP_012834241.1; NC_013441.1.
DR   AlphaFoldDB; D0LDR3; -.
DR   STRING; 526226.Gbro_2445; -.
DR   KEGG; gbr:Gbro_2445; -.
DR   eggNOG; COG0646; Bacteria.
DR   eggNOG; COG1410; Bacteria.
DR   HOGENOM; CLU_004914_4_0_11; -.
DR   UniPathway; UPA00051; UER00081.
DR   Proteomes; UP000001219; Chromosome.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
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:0050667; P:homocysteine metabolic process; IEA:TreeGrafter.
DR   GO; GO:0046653; P:tetrahydrofolate metabolic process; IEA:TreeGrafter.
DR   CDD; cd02069; methionine_synthase_B12_BD; 1.
DR   CDD; cd00740; MeTr; 1.
DR   FunFam; 1.10.1240.10:FF:000002; Methionine synthase; 1.
DR   FunFam; 3.20.20.20:FF:000007; Methionine synthase; 1.
DR   FunFam; 3.20.20.330:FF:000006; Methionine synthase; 1.
DR   FunFam; 3.40.50.280:FF:000004; Methionine synthase; 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; 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; IPR050554; Met_Synthase/Corrinoid.
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 {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:UP000001219};
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          17..321
FT                   /note="Hcy-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50970"
FT   DOMAIN          352..615
FT                   /note="Pterin-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50972"
FT   DOMAIN          644..737
FT                   /note="B12-binding N-terminal"
FT                   /evidence="ECO:0000259|PROSITE:PS51337"
FT   DOMAIN          737..874
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS51332"
FT   DOMAIN          901..1199
FT                   /note="AdoMet activation"
FT                   /evidence="ECO:0000259|PROSITE:PS50974"
FT   BINDING         240
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         306
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         307
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         747..751
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         750
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         795
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         853
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         948
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         1142
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         1196..1197
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ   SEQUENCE   1199 AA;  130734 MW;  4F71BBF1480F805E CRC64;
     MSSVSRPDHS TDPADFDTTF MSAMSRRVLI GDGAMGTMLQ AADLTLDDFN GLEGCNEILN
     DARPDVLEGI HRAYFEAGAD AVETNTFGCN LSNLGDYDIA DRIRELAYKG TGIARGVADE
     MGPTANGTDR FVLGSIGPGT KLPSLGHTTF AVIRDAYFEC VAGMLDGGAD AILIETSQDL
     LQVKAAVVAA RRAMDKLGRR IPIISHVTVE TTGTMLLGSE IGAALTAIEP LGVDMIGLNC
     ATGPAEMSEH LRYLSRHARI PVSVMPNAGL PVLGPNGAEY PLSPEELAQA LHGFVAEFGL
     DFVGGCCGTT PEHIRQVAEA VHGATPAART PEHASETSSL YTAVPFDQDA SFLVIGERTN
     TNGSKAFREA MIAGDYQRCL DIAKDQTRDG AHMLDLNVDY VGRDGAVDMT ALASRFATSS
     TLPIMLDSTE PEVIRAGLET LGGRCAVNSV NYEDGDGPNS RFTRIMQLVV EHGAAVVALT
     IDEEGQARTA DWKVRIAERL IADITGNWGL AEEDIIIDAL TFPISTGQEE VRRDGIETIE
     AIRRIHEAHP EVHFTLGISN ISFGLNPAAR QVLNSVFLHE CVQAGLDTAI VHASKILPMA
     RIPEEHRKVA LDLVYDRRAP GYDPLQKLME LFEGVSAASA RESRAAELAK LPLFERLERR
     IVDGERNGLE DDLDEAMTTV PPLKIINETL LSGMKTVGEL FGSGQMQLPF VLQSAEVMKT
     AVAHLEPHME STGEDGKGRI VLATVKGDVH DIGKNLVDII LSNNGYEVVN IGIKQPITNI
     LDVAADKKVD VIGMSGLLVK STVVMKENLE EINARGLADE YPVLLGGAAL TRSYVENDLS
     ETYEGDVHYA RDAFEGLRLM DEIMATKRGE GPDPDSPEAI AAAEKAAERK ARHDRSKRIA
     AKRKAAEEPV EVPARSDVAA DNDIPAPPFW GTRIVKGVPV ADYLQLLDER ALFLGQWGLR
     GARGGDGPSY EDLVESEGRP RLRYWIDRLA TEGILQHAAV VYGYFPAVSD GDTVHVLTEP
     RPDAPVRYSF GFPRQQRSRF LCIADFIRSR EDAIRDGHVD VLPFQLVTMG QPIADFANEL
     FAADAYRDYL EVHGIGVQLT EALAEYWHQR VRSELRFGER TMDSEDPDEA QGFFDLEYRG
     ARFSFGYGAC PDLDDRAKMM ELLQPERIGV HLSEELQLHP EQSTDAFVLH HPEAKYFNT
//