ID   DYR_STAEP               Reviewed;         161 AA.
AC   P0C0P0; Q59908;
DT   22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2005, sequence version 1.
DT   27-MAR-2024, entry version 88.
DE   RecName: Full=Dihydrofolate reductase;
DE            Short=DHFR;
DE            EC=1.5.1.3;
GN   Name=folA; Synonyms=dfrC, folA1;
OS   Staphylococcus epidermidis.
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1282;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND MUTAGENESIS.
RC   STRAIN=ATCC 14990 / DSM 20044 / CIP 81.55 / NCTC 11047;
RX   PubMed=7768789; DOI=10.1128/jb.177.11.2965-2970.1995;
RA   Dale G.E., Broger C., Hartman P.G., Langen H., Page M.G.P., Then R.L.,
RA   Stueber D.;
RT   "Characterization of the gene for the chromosomal dihydrofolate reductase
RT   (DHFR) of Staphylococcus epidermidis ATCC 14990: the origin of the
RT   trimethoprim-resistant S1 DHFR from Staphylococcus aureus?";
RL   J. Bacteriol. 177:2965-2970(1995).
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   -!- MISCELLANEOUS: Trimethoprim sensitive.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; Z48233; CAA88269.1; -; Genomic_DNA.
DR   PIR; A57271; A57271.
DR   RefSeq; WP_001830952.1; NZ_WLVA01000001.1.
DR   AlphaFoldDB; P0C0P0; -.
DR   SMR; P0C0P0; -.
DR   GeneID; 50018758; -.
DR   PATRIC; fig|1282.1160.peg.1857; -.
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   1: Evidence at protein level;
KW   NADP; One-carbon metabolism; Oxidoreductase.
FT   CHAIN           1..161
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186413"
FT   DOMAIN          2..157
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         6..8
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         7..8
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         15..20
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         28
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         44..47
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         63..66
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         93..98
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         112
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         32
FT                   /note="V->I: 3-fold increase of KM for dihydrofolate."
FT                   /evidence="ECO:0000269|PubMed:7768789"
FT   MUTAGEN         44
FT                   /note="G->A: 5-fold increase of KM for NADPH."
FT                   /evidence="ECO:0000269|PubMed:7768789"
FT   MUTAGEN         99
FT                   /note="F->Y: Trimethoprim resistance."
FT                   /evidence="ECO:0000269|PubMed:7768789"
SQ   SEQUENCE   161 AA;  18417 MW;  CB3167940A387EE0 CRC64;
     MTLSIIVAHD KQRVIGYQNQ LPWHLPNDLK HVKQLTTGNT LVMGRKTFNS IGKPLPNRRN
     VVLTNQASFH HEGVDVINSL DEIKELSGHV FIFGGQTLFE AMIDQVDDMY ITVIDGKFQG
     DTFFPPYTFE NWEVESSVEG QLDEKNTIPH TFLHLVRRKG K
//