METH_MYCLE
ID METH_MYCLE Reviewed; 1206 AA.
AC Q49775; Q9CC37; Q9S378;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 3.
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=ML1307; ORFNames=B2126_C1_157, MLCB2533.04;
OS Mycobacterium leprae (strain TN).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=272631;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Smith D.R., Robison K.;
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=TN;
RX PubMed=11234002; DOI=10.1038/35059006;
RA Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA Barrell B.G.;
RT "Massive gene decay in the leprosy bacillus.";
RL Nature 409:1007-1011(2001).
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA17182.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA22918.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U00017; AAA17182.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AL035310; CAA22918.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL583921; CAC31688.1; -; Genomic_DNA.
DR PIR; E87072; E87072.
DR PIR; S72842; S72842.
DR RefSeq; NP_301940.1; NC_002677.1.
DR RefSeq; WP_010908261.1; NC_002677.1.
DR AlphaFoldDB; Q49775; -.
DR SMR; Q49775; -.
DR STRING; 272631.ML1307; -.
DR EnsemblBacteria; CAC31688; CAC31688; CAC31688.
DR KEGG; mle:ML1307; -.
DR PATRIC; fig|272631.5.peg.2411; -.
DR Leproma; ML1307; -.
DR eggNOG; COG0646; Bacteria.
DR eggNOG; COG1410; Bacteria.
DR HOGENOM; CLU_004914_4_0_11; -.
DR OMA; ADCIAMS; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000000806; Chromosome.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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..1206
FT /note="Methionine synthase"
FT /id="PRO_0000204533"
FT DOMAIN 1..314
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 350..609
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 642..735
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 740..877
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 907..1206
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT REGION 873..925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 885..924
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 233
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 750..754
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 753
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 798
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 856
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 954
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1149
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1203..1204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1206 AA; 132392 MW; 7786CE5307D7CA86 CRC64;
MRVTAANQHQ YDTDLLETLA QRVMVGDGAM GTQLQDAELT LDDFRGLEGC NEILNETRPD
VLETIHRRYF EAGADLVETN TFGCNLSNLG DYDIADKIRD LSQRGTVIAR RVADELTTPD
HKRYVLGSMG PGTKLPTLGH TEYRVVRDAY TESALGMLDG GADAVLVETC QDLLQLKAAV
LGSRRAMTQA GRHIPVFVHV TVETTGTMLL GSEIGAALAA VEPLGVDMIG LNCATGPAEM
SEHLRHLSKH ARIPVSVMPN AGLPVLGAKG AEYPLQPDEL AEALAGFIAE FGLSLVGGCC
GTTPDHIREV AAAVARCNDG TVPRGERHVT YEPSVSSLYT AIPFAQKPSV LMIGERTNAN
GSKVFREAMI AEDYQKCLDI AKDQTRGGAH LLDLCVDYVG RNGVADMKAL AGRLATVSTL
PIMLDSTEIP VLQAGLEHLG GRCVINSVNY EDGDGPESRF VKTMELVAEH GAAVVALTID
EQGQARTVEK KVEVAERLIN DITSNWGVDK SAILIDCLTF TIATGQEESR KDGIETIDAI
RELKKRHPAV QTTLGLSNIS FGLNPSARQV LNSVFLHECQ EAGLDSAIVH ASKILPINRI
PEEQRQAALD LVYDRRREGY DPLQKLMWLF KGVSSPSSKE TREAELAKLP LFDRLAQRIV
DGERNGLDVD LDEAMTQKPP LAIINENLLD GMKTVGELFG SGQMQLPFVL QSAEVMKAAV
AYLEPHMEKS DCDFGKGLAK GRIVLATVKG DVHDIGKNLV DIILSNNGYE VVNLGIKQPI
TNILEVAEDK SADVVGMSGL LVKSTVIMKE NLEEMNTRGV AEKFPVLLGG AALTRSYVEN
DLAEVYEGEV HYARDAFEGL KLMDTIMSAK RGEALAPGSP ESLAAEADRN KETERKARHE
RSKRIAVQRK AAEEPVEVPE RSDVPSDVEV PAPPFWGSRI IKGLAVADYT GFLDERALFL
GQWGLRGVRG GAGPSYEDLV QTEGRPRLRY WLDRLSTYGV LAYAAVVYGY FPAVSEDNDI
VVLAEPRPDA EQRYRFTFPR QQRGRFLCIA DFIRSRDLAT ERSEVDVLPF QLVTMGQPIA
DFVGELFVSN SYRDYLEVHG IGVQLTEALA EYWHRRIREE LKFSGNRTMS ADDPEAVEDY
FKLGYRGARF AFGYGACPDL EDRIKMMELL QPERIGVTIS EELQLHPEQS TDAFVLHHPA
AKYFNV
