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-MAY-2023, entry version 111.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA; Synonyms=atsR;
OS   Klebsiella aerogenes (Enterobacter aerogenes).
OC   Bacteria; Pseudomonadota; 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   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; Dihydrofolate Reductase, subunit A; 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; DIHYDROFOLATE REDUCTASE; 1.
DR   PANTHER; PTHR48069:SF3; DIHYDROFOLATE REDUCTASE; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   PIRSF; PIRSF000194; DHFR; 1.
DR   PRINTS; PR00070; DHFR.
DR   SUPFAM; SSF53597; Dihydrofolate reductase-like; 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
//