ID   DYR_MYCLE               Reviewed;         165 AA.
AC   Q9CBW1;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=folA; OrderedLocusNames=ML1518;
OS   Mycobacterium leprae (strain TN).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium.
OX   NCBI_TaxID=272631;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=TN;
RX   PubMed=11234002; DOI=10.1038/35059006;
RA   Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA   Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA   Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA   Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA   Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA   Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA   Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA   Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA   Barrell B.G.;
RT   "Massive gene decay in the leprosy bacillus.";
RL   Nature 409:1007-1011(2001).
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AL583922; CAC30469.1; -; Genomic_DNA.
DR   PIR; H87098; H87098.
DR   RefSeq; NP_302063.1; NC_002677.1.
DR   RefSeq; WP_010908384.1; NC_002677.1.
DR   AlphaFoldDB; Q9CBW1; -.
DR   SMR; Q9CBW1; -.
DR   STRING; 272631.ML1518; -.
DR   PRIDE; Q9CBW1; -.
DR   EnsemblBacteria; CAC30469; CAC30469; CAC30469.
DR   KEGG; mle:ML1518; -.
DR   PATRIC; fig|272631.5.peg.2861; -.
DR   Leproma; ML1518; -.
DR   eggNOG; COG0262; Bacteria.
DR   HOGENOM; CLU_043966_5_0_11; -.
DR   OMA; RDNQLPW; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000000806; 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; -; 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; PTHR48069; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   PIRSF; PIRSF000194; DHFR; 1.
DR   SUPFAM; SSF53597; SSF53597; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   3: Inferred from homology;
KW   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..165
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186399"
FT   DOMAIN          3..165
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         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   165 AA;  18509 MW;  E6A76965BFBEC74F CRC64;
     MTVVGLIWAQ STTGVIGRDG GMPWRVPEDL TRFKQLTMGH PVVMGRRTWD SLPVGVRPLP
     GRRNIVLSRQ IDFMAEGAEV FGSLEETISN LETEPEMWVI GGEQIYRLAL PLATRCGVTE
     VDTYLLHEDD DVLAPVLDDT WVGVTGEWLV SCSGLRYRLH SYHRS