ID   DYR_STAAR               Reviewed;         159 AA.
AC   Q6GGY1;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 109.
DE   RecName: Full=Dihydrofolate reductase;
DE            Short=DHFR;
DE            EC=1.5.1.3;
GN   Name=folA; OrderedLocusNames=SAR1439;
OS   Staphylococcus aureus (strain MRSA252).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=282458;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MRSA252;
RX   PubMed=15213324; DOI=10.1073/pnas.0402521101;
RA   Holden M.T.G., Feil E.J., Lindsay J.A., Peacock S.J., Day N.P.J.,
RA   Enright M.C., Foster T.J., Moore C.E., Hurst L., Atkin R., Barron A.,
RA   Bason N., Bentley S.D., Chillingworth C., Chillingworth T., Churcher C.,
RA   Clark L., Corton C., Cronin A., Doggett J., Dowd L., Feltwell T., Hance Z.,
RA   Harris B., Hauser H., Holroyd S., Jagels K., James K.D., Lennard N.,
RA   Line A., Mayes R., Moule S., Mungall K., Ormond D., Quail M.A.,
RA   Rabbinowitsch E., Rutherford K.M., Sanders M., Sharp S., Simmonds M.,
RA   Stevens K., Whitehead S., Barrell B.G., Spratt B.G., Parkhill J.;
RT   "Complete genomes of two clinical Staphylococcus aureus strains: evidence
RT   for the rapid evolution of virulence and drug resistance.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:9786-9791(2004).
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; BX571856; CAG40436.1; -; Genomic_DNA.
DR   RefSeq; WP_000175746.1; NC_002952.2.
DR   AlphaFoldDB; Q6GGY1; -.
DR   SMR; Q6GGY1; -.
DR   KEGG; sar:SAR1439; -.
DR   HOGENOM; CLU_043966_5_1_9; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000000596; Chromosome.
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   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..159
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186409"
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"
SQ   SEQUENCE   159 AA;  18251 MW;  811898409FEAFAAB CRC64;
     MTLSILVAHD LQRVIGFENQ LPWHLPNDLK HVKKLSTGHT LVMGRKTFES IGKPLPNRRN
     VVLTSDTSFN VEGVDVIHSI EDIYQLPGHV FIFGGQTLFE EMIDKVDDMY ITVIEGKFRG
     DTFFPPYTFE DWEVASSVEG KLDEKNTIPH TFLHLIRKK
//