METH_PSEAE
ID METH_PSEAE Reviewed; 1234 AA.
AC Q9I2Q2;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 121.
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=PA1843;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
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; AE004091; AAG05232.1; -; Genomic_DNA.
DR PIR; E83415; E83415.
DR RefSeq; NP_250534.1; NC_002516.2.
DR RefSeq; WP_003113602.1; NZ_QZGE01000003.1.
DR AlphaFoldDB; Q9I2Q2; -.
DR SMR; Q9I2Q2; -.
DR STRING; 287.DR97_34; -.
DR PaxDb; Q9I2Q2; -.
DR PRIDE; Q9I2Q2; -.
DR EnsemblBacteria; AAG05232; AAG05232; PA1843.
DR GeneID; 880631; -.
DR KEGG; pae:PA1843; -.
DR PATRIC; fig|208964.12.peg.1916; -.
DR PseudoCAP; PA1843; -.
DR HOGENOM; CLU_004914_2_1_6; -.
DR InParanoid; Q9I2Q2; -.
DR OMA; ADCIAMS; -.
DR PhylomeDB; Q9I2Q2; -.
DR BioCyc; PAER208964:G1FZ6-1882-MON; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000002438; Chromosome.
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..1234
FT /note="Methionine synthase"
FT /id="PRO_0000287780"
FT DOMAIN 12..332
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 363..624
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 655..749
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 752..888
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 904..1234
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 254
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 318
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 762..766
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 765
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 810
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 814
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 867
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 1142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1197..1198
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1234 AA; 135063 MW; 9877F8AC8BEF44ED CRC64;
MSSPLTDRSA RLQALQHALR ERILILDGGM GTMIQSYKLE EADYRGERFA DWPSDVKGNN
DLLLLSRPDV IQAIEKAYLD AGADILETNT FNATQVSQAD YGMQSLAYEL NVEGARLARQ
VADAKTAETP DKPRFVAGVL GPTSRTCSIS PDVNNPGYRN VTFDELVENY VEATRGLIEG
GADLILIETI FDTLNAKAAI FAVQGVFEEL GVELPIMISG TITDASGRTL SGQTTEAFWN
SVRHARPISV GLNCALGAKE LRPYIEELST KADTHVSAHP NAGLPNAFGE YDESPAEMAV
VVEEFAAAGF LNIVGGCCGT TPAHIEAIAK AVAKYPPRAI PEIPRACRLS GLEPFTIDRS
SLFVNVGERT NITGSAKFAR LIREENYAEA LEVAQQQVEA GAQVIDINMD EGMLDSKAAM
VTFLNLIASE PDISRVPIMI DSSKWEVIEA GLKCIQGKGI VNSISMKEGV EAFKHHARLC
KRYGAAVVVM AFDEDGQADT QARKEEICKR SYDILVDEVG FPPEDIIFDA NIFAIATGIE
EHNNYAVDFI NACAYIRDNL PYALSSGGVS NVSFSFRGNN PVREAIHSVF LYYAIRNGLT
MGIVNAGQLE IYDEIPKALR DRVEDVVLNR TPEATEALLA IADDYKGGGA VKEAEDEEWR
SYSVEKRLEH ALVKGITTWI VEDTEECRQQ CARPIEVIEG PLMSGMNVVG DLFGAGKMFL
PQVVKSARVM KQAVAHLIPF IEAEKGDKPE AKGKILMATV KGDVHDIGKN IVGVVLGCNG
YDVVDLGVMV PAEKILQTAI AEKCDIIGLS GLITPSLDEM VHVAKEMQRQ NFQLPLMIGG
ATTSKAHTAV KIDPQYSNDA VVYVTDASRA VGVATSLLSK ELKADYVART RADYAVVRER
TANRSARTER LSYEQAIANK PAFDWAGYQA PTPSFTGVRV LDEIDLAVLA EYIDWTPFFI
SWDLAGKYPR ILTDEVVGEA ATSLFNDAQA MLKKLIDEKL IKARAVFGFW PANQVEHDDL
EVYGADGETL ATLHHLRQQT IKPDGKPNLS LADFVAPKES GVRDYIGGFI TTAGIGAEEV
AKAYEAKGDD YNSIMVKALA DRLAEACAEW LHERVRKEYW GYARDEHLDN EALIKEQYVG
IRPAPGYPAC PDHTEKGTLF ELLDPQGLSG VSLTEHYAMF PAAAVSGWYF AHPQAQYFAV
GKIDKDQVER YSQRKGQEAS VSERWLAPNL GYDD
