ID   DYR_ENTFC               Reviewed;         167 AA.
AC   P00380;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 95.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA;
OS   Enterococcus faecium (Streptococcus faecium).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC   Enterococcus.
OX   NCBI_TaxID=1352;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   STRAIN=A / var. Durans;
RX   PubMed=1097435; DOI=10.1016/s0021-9258(19)41260-x;
RA   Peterson D.L., Gleisner J.M., Blakley R.L.;
RT   "The structure of the mutant dihydrofolate reductase from Streptococcus
RT   faecium. Amino acid sequence of peptide CNBr 7 and complete sequence of the
RT   protein.";
RL   J. Biol. Chem. 250:4945-4954(1975).
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   PIR; A00392; RDSODF.
DR   AlphaFoldDB; P00380; -.
DR   SMR; P00380; -.
DR   ChEMBL; CHEMBL3243913; -.
DR   DrugCentral; P00380; -.
DR   SABIO-RK; P00380; -.
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   1: Evidence at protein level;
KW   Direct protein sequencing; NADP; One-carbon metabolism; Oxidoreductase.
FT   CHAIN           1..167
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186390"
FT   DOMAIN          1..162
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
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         58
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         64..65
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         99..106
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         117
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   167 AA;  19583 MW;  E00C2CF3BC420585 CRC64;
     MFISMWAQDK NGLIGKDGLL PWRLPNDMRF FREHTMDKIL VMGRKTYEGM GKLSLPYRHI
     IVLTTQKDFK VEKNAEVLHS IDELLAYAKD IPEDIYVSGG SRIFQALLPE TKIIWRTLID
     AEFEGDTFIG EIDFTSFELV EEHEGIVNQE NQYPHRFQKW QKMSKVV