ID   DYR_CITFR               Reviewed;         159 AA.
AC   P31073;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   03-AUG-2022, entry version 96.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA;
OS   Citrobacter freundii.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Citrobacter; Citrobacter freundii complex.
OX   NCBI_TaxID=546;
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).
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; M26023; AAA23093.1; -; Genomic_DNA.
DR   PIR; B39799; B39799.
DR   RefSeq; WP_003018873.1; NZ_VTEC01000065.1.
DR   AlphaFoldDB; P31073; -.
DR   SMR; P31073; -.
DR   STRING; 1333848.CFNIH1_09955; -.
DR   GeneID; 58318192; -.
DR   GeneID; 67517762; -.
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_0000186386"
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"
SQ   SEQUENCE   159 AA;  18028 MW;  3CE7D7688577DCEE CRC64;
     MISLIAALAV DRVIGMENAM PWNLPADLAW FKRNTLNKPV VMGRHTWESI GRPLPGRKNI
     VISSKPGTDD RVQWVKSVDE AIAACGDEPE IMVIGGGRVY EQFLPKAQKL YLTHIDAEVE
     GDTHFPDYEP DDWESVFSEF HDADAQNSHS YCFEILERR