ID   DYR_STAHA               Reviewed;         166 AA.
AC   Q54277;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 92.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=dfrD;
OS   Staphylococcus haemolyticus.
OG   Plasmid pABU17.
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1283;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND MASS SPECTROMETRY.
RC   STRAIN=MUR313;
RX   PubMed=8540692; DOI=10.1128/aac.39.9.1920;
RA   Dale G.E., Langen H., Page M.G., Then R.L., Stueber D.;
RT   "Cloning and characterization of a novel, plasmid-encoded trimethoprim-
RT   resistant dihydrofolate reductase from Staphylococcus haemolyticus
RT   MUR313.";
RL   Antimicrob. Agents Chemother. 39:1920-1924(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   -!- MASS SPECTROMETRY: Mass=19821.2; Mass_error=2; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:8540692};
CC   -!- MISCELLANEOUS: Confers trimethoprim resistance.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; Z50141; CAA90486.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q54277; -.
DR   SMR; Q54277; -.
DR   STRING; 1283.ShL2_01296; -.
DR   KEGG; ag:CAA90486; -.
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:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   GO; GO:0031427; P:response to methotrexate; 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   Antibiotic resistance; Methotrexate resistance; NADP;
KW   One-carbon metabolism; Oxidoreductase; Plasmid; Trimethoprim resistance.
FT   CHAIN           1..166
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186416"
FT   DOMAIN          6..164
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         10..12
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         11..12
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         19..24
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         32
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         48..51
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         62
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         67..70
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         100..105
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         119
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   166 AA;  19825 MW;  9AAD03F3ECCA9990 CRC64;
     MWSFLKISLI VAMDKKRVIG KDNDIPWRIS SDWEYVKNTT KGHAIILGRK NLQSIGRALP
     DRRNIILTRD KNFNFKDCEI AHSIEAAFKL CENEEEVFIF GGEQIYVMFL PYVEKMYVTK
     IHHEFEGDTF FPVVNFDDWK EVSVEKGIKD EKNPYDYYFH IYERIR
//