DYR_KLEAE
ID DYR_KLEAE Reviewed; 159 AA.
AC P31074; P27498;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=folA; Synonyms=atsR;
OS Klebsiella aerogenes (Enterobacter aerogenes).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Klebsiella/Raoultella group; Klebsiella.
OX NCBI_TaxID=548;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1766362; DOI=10.1093/oxfordjournals.molbev.a040676;
RA Garvin L.D., Hardies S.C.;
RT "Temporal and topological clustering of diverged residues among
RT enterobacterial dihydrofolate reductases.";
RL Mol. Biol. Evol. 8:654-668(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=W70;
RX PubMed=1551851; DOI=10.1128/jb.174.7.2344-2351.1992;
RA Azakami H., Sugino H., Murooka Y.;
RT "Cloning and nucleotide sequence of a negative regulator gene for
RT Klebsiella aerogenes arylsulfatase synthesis and identification of the gene
RT as folA.";
RL J. Bacteriol. 174:2344-2351(1992).
CC -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential
CC reaction for de novo glycine and purine synthesis, and for DNA
CC precursor synthesis (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00660};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; M26022; AAA24800.1; -; Genomic_DNA.
DR EMBL; D10358; BAA01187.1; -; Genomic_DNA.
DR PIR; A39799; A39799.
DR RefSeq; WP_015368294.1; NZ_WPHE01000007.1.
DR AlphaFoldDB; P31074; -.
DR SMR; P31074; -.
DR STRING; 548.EAG7_03293; -.
DR ChEMBL; CHEMBL3853; -.
DR GeneID; 66605527; -.
DR OMA; RDNQLPW; -.
DR OrthoDB; 1920912at2; -.
DR UniPathway; UPA00077; UER00158.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR Gene3D; 3.40.430.10; -; 1.
DR InterPro; IPR012259; DHFR.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
DR PANTHER; PTHR48069; PTHR48069; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR PIRSF; PIRSF000194; DHFR; 1.
DR SUPFAM; SSF53597; SSF53597; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
PE 3: Inferred from homology;
KW NADP; One-carbon metabolism; Oxidoreductase.
FT CHAIN 1..159
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186389"
FT DOMAIN 1..158
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 5
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 7
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 13..19
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 27
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 45..46
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 52
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 63..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 76
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 95..102
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 9
FT /note="A -> R (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 23..26
FT /note="DLPA -> NLNE (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="K -> S (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="D -> E (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="A -> V (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 101..102
FT /note="EQ -> DE (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="H -> Q (in Ref. 2; BAA01187)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 159 AA; 17974 MW; 73C9B8D31D0C1C07 CRC64;
MISLIAALAV DRVIGMENAM PWDLPADLAW FKRNTLNKPV VMGRLTWESI GRPLPGRKNI
VISSKPGSDD RVQWVKSVDE AIAACGDAEE IMVIGGGRVY EQFLPKAHKL YLTHIDAEVE
GDTHFPDYDP DEWESVFSEF HDADAQNSHS YCFEILERR
