ID   DYR_NEIGO               Reviewed;         162 AA.
AC   P04174;
DT   20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT   20-MAR-1987, sequence version 1.
DT   24-JAN-2024, entry version 94.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA;
OS   Neisseria gonorrhoeae.
OC   Bacteria; Pseudomonadota; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC   Neisseria.
OX   NCBI_TaxID=485;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   STRAIN=T47/F62;
RX   PubMed=6434541; DOI=10.1016/s0021-9258(20)71353-0;
RA   Baccanari D.P., Tansik R.L., Paterson S.J., Stone D.;
RT   "Characterization and amino acid sequence of Neisseria gonorrhoeae
RT   dihydrofolate reductase.";
RL   J. Biol. Chem. 259:12291-12298(1984).
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: Strain T47/F62 is trimethoprim resistant by
CC       overproduction of DHFR.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   PIR; A00393; RDNHD.
DR   AlphaFoldDB; P04174; -.
DR   SMR; P04174; -.
DR   ChEMBL; CHEMBL3565; -.
DR   DrugCentral; P04174; -.
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: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; Direct protein sequencing; NADP;
KW   One-carbon metabolism; Oxidoreductase; Trimethoprim resistance.
FT   CHAIN           1..162
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186401"
FT   DOMAIN          3..161
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         7..9
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         8..9
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         16..21
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         29
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         45..48
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         60
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         65..68
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         98..103
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   162 AA;  17731 MW;  A23BA94E6764E564 CRC64;
     MLKITIIAAC AENLCIGAGN AMPWHIPEDF AFFKVYTLGK PVIMGRKTWE SLPVKPLPGR
     RNIVISRQAD YCAAGAETVA SLEVALALCA GAEEAVIMGG AQIYGQAMPL ATDLRITEVD
     LSVEGDAFFP EIDRTHWREA ERTERRVSSK GVAYTFVHYL GK
//