ID   DYR23_ECOLX             Reviewed;          78 AA.
AC   P05794;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   03-MAY-2023, entry version 104.
DE   RecName: Full=Dihydrofolate reductase type 2;
DE            EC=1.5.1.3;
DE   AltName: Full=Dihydrofolate reductase type II;
OS   Escherichia coli.
OG   Plasmid IncP-beta R751.
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=562;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3526286; DOI=10.1093/nar/14.14.5933;
RA   Flensburg J., Steen R.;
RT   "Nucleotide sequence analysis of the trimethoprim resistant dihydrofolate
RT   reductase encoded by R plasmid R751.";
RL   Nucleic Acids Res. 14:5933-5933(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Radstroem P., Sundstroem L., Swedberg G., Flensburg J., Skoeld O.;
RL   Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Thomas C.M.;
RL   Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
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;
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC       tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- DOMAIN: The active site is situated at the inner surface of a pore
CC       formed by the four subunits. {ECO:0000250}.
CC   -!- MISCELLANEOUS: Type II plasmid-specified enzyme is practically
CC       insensitive to trimethoprim and methotrexate.
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DR   EMBL; X04128; CAA27740.1; -; Genomic_DNA.
DR   EMBL; X72585; CAA51181.1; -; Genomic_DNA.
DR   EMBL; U67194; AAC64461.1; -; Genomic_DNA.
DR   PIR; A23598; RDECD5.
DR   PIR; S32183; S32183.
DR   RefSeq; WP_010890144.1; NZ_KU997026.1.
DR   AlphaFoldDB; P05794; -.
DR   SMR; P05794; -.
DR   KEGG; ag:CAA51181; -.
DR   UniPathway; UPA00077; UER00158.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
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:0009410; P:response to xenobiotic stimulus; IEA:InterPro.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 2.30.30.60; -; 1.
DR   InterPro; IPR009159; Dhfr_type_II.
DR   InterPro; IPR008990; Elect_transpt_acc-like_dom_sf.
DR   InterPro; IPR023408; MscS_beta-dom_sf.
DR   Pfam; PF06442; DHFR_2; 1.
DR   PIRSF; PIRSF000199; Dhfr_type_II; 1.
DR   SUPFAM; SSF50090; Electron transport accessory proteins; 1.
PE   3: Inferred from homology;
KW   Antibiotic resistance; Methotrexate resistance; NADP;
KW   One-carbon metabolism; Oxidoreductase; Plasmid; Trimethoprim resistance.
FT   CHAIN           1..78
FT                   /note="Dihydrofolate reductase type 2"
FT                   /id="PRO_0000186437"
FT   BINDING         32
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         66..69
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         68
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   78 AA;  8328 MW;  3D67C2EB67220697 CRC64;
     MDQHNNGVST LVAGQFALPS HATFGLGDRV RKKSGAAWQG QVVGWYCTKL TPEGYAVESE
     SHPGSVQIYP VAALERVA
//