DYR_CANAX
ID DYR_CANAX Reviewed; 192 AA.
AC P22906; O59840;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 4.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=DFR1;
OS Candida albicans (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=5476;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=10127/5;
RX PubMed=7916311; DOI=10.1016/0378-1119(94)90049-3;
RA Daly S., Mastromei G., Yacoub A., Lorenzetti R.;
RT "Sequence of a dihydrofolate reductase-encoding gene from Candida
RT albicans.";
RL Gene 147:115-118(1994).
RN [2]
RP PROTEIN SEQUENCE OF 1-25, AND NUCLEOTIDE SEQUENCE OF 26-36.
RX PubMed=2642898; DOI=10.1016/s0021-9258(19)85059-7;
RA Baccanari D.P., Tansik R.L., Joyner S.S., Fling M.E., Smith P.L.,
RA Freisheim J.H.;
RT "Characterization of Candida albicans dihydrofolate reductase.";
RL J. Biol. Chem. 264:1100-1107(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND X-RAY CRYSTALLOGRAPHY (1.85
RP ANGSTROMS).
RC STRAIN=SYNTEX CA755;
RX PubMed=9374515; DOI=10.1074/jbc.272.48.30289;
RA Whitlow M., Howard A.J., Stewart D., Hardman K.D., Kuyper L.F.,
RA Baccanari D.P., Fling M.E., Tansik R.L.;
RT "X-ray crystallographic studies of Candida albicans dihydrofolate
RT reductase. High resolution structures of the holoenzyme and an inhibited
RT ternary complex.";
RL J. Biol. Chem. 272:30289-30298(1997).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH NADPH AND INHIBITOR.
RX PubMed=11520201; DOI=10.1021/jm0101444;
RA Whitlow M., Howard A.J., Stewart D., Hardman K.D., Chan J.H.,
RA Baccanari D.P., Tansik R.L., Hong J.S., Kuyper L.F.;
RT "X-Ray crystal structures of Candida albicans dihydrofolate reductase: high
RT resolution ternary complexes in which the dihydronicotinamide moiety of
RT NADPH is displaced by an inhibitor.";
RL J. Med. Chem. 44:2928-2932(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.
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; X78968; CAA55561.1; -; Genomic_DNA.
DR EMBL; U84588; AAC05610.1; -; Genomic_DNA.
DR PIR; A32203; A32203.
DR PDB; 1AI9; X-ray; 1.85 A; A/B=1-192.
DR PDB; 1AOE; X-ray; 1.60 A; A/B=1-192.
DR PDB; 1IA1; X-ray; 1.70 A; A/B=1-192.
DR PDB; 1IA2; X-ray; 1.82 A; A/B=1-192.
DR PDB; 1IA3; X-ray; 1.78 A; A/B=1-192.
DR PDB; 1IA4; X-ray; 1.85 A; A/B=1-192.
DR PDB; 1M78; X-ray; 1.71 A; A/B=1-192.
DR PDB; 1M79; X-ray; 1.70 A; A/B=1-192.
DR PDB; 1M7A; X-ray; 1.76 A; A/B=1-192.
DR PDB; 3QLR; X-ray; 2.15 A; A/B=3-192.
DR PDB; 3QLS; X-ray; 1.73 A; A/B=3-192.
DR PDB; 3QLW; X-ray; 2.50 A; A/B=3-192.
DR PDB; 4H95; X-ray; 2.60 A; A/B=4-192.
DR PDB; 4H96; X-ray; 2.60 A; A/B=4-192.
DR PDB; 4H97; X-ray; 2.20 A; A/B=3-192.
DR PDB; 4HOE; X-ray; 1.76 A; A/B=1-192.
DR PDB; 4HOF; X-ray; 1.76 A; A/B=1-192.
DR PDBsum; 1AI9; -.
DR PDBsum; 1AOE; -.
DR PDBsum; 1IA1; -.
DR PDBsum; 1IA2; -.
DR PDBsum; 1IA3; -.
DR PDBsum; 1IA4; -.
DR PDBsum; 1M78; -.
DR PDBsum; 1M79; -.
DR PDBsum; 1M7A; -.
DR PDBsum; 3QLR; -.
DR PDBsum; 3QLS; -.
DR PDBsum; 3QLW; -.
DR PDBsum; 4H95; -.
DR PDBsum; 4H96; -.
DR PDBsum; 4H97; -.
DR PDBsum; 4HOE; -.
DR PDBsum; 4HOF; -.
DR AlphaFoldDB; P22906; -.
DR SMR; P22906; -.
DR BindingDB; P22906; -.
DR ChEMBL; CHEMBL2329; -.
DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR DrugBank; DB02402; 5-(4-Methoxyphenoxy)-2,4-Quinazolinediamine.
DR DrugBank; DB02001; 5-(4-Morpholin-4-Yl-Phenylsulfanyl)-2,4-Quinazolinediamine.
DR DrugBank; DB04306; 5-[(4-Methylphenyl)Sulfanyl]-2,4-Quinazolinediamine.
DR DrugBank; DB01958; 5-[4-Tert-Butylphenylsulfanyl]-2,4-Quinazolinediamine.
DR DrugBank; DB01929; 5-Chloryl-2,4,6-quinazolinetriamine.
DR DrugBank; DB04163; 5-Phenylsulfanyl-2,4-Quinazolinediamine.
DR DrugCentral; P22906; -.
DR VEuPathDB; FungiDB:C7_03130C_A; -.
DR VEuPathDB; FungiDB:CAWG_05646; -.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; P22906; -.
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 SUPFAM; SSF53597; SSF53597; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; NADP; One-carbon metabolism;
KW Oxidoreductase.
FT CHAIN 1..192
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186374"
FT DOMAIN 5..191
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 11
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11520201"
FT BINDING 18..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11520201"
FT BINDING 32..37
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11520201"
FT BINDING 56..58
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11520201"
FT BINDING 72
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT BINDING 78..80
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11520201"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11520201"
FT BINDING 113..120
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11520201"
FT BINDING 118
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11520201"
FT VARIANT 2
FT /note="S -> L (in strain: SYNTEX CA755)"
FT VARIANT 84
FT /note="K -> E (in strain: SYNTEX CA755)"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:1AOE"
FT TURN 14..17
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:1IA1"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 56..61
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:4H96"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 127..136
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1AOE"
FT HELIX 161..168
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:1AOE"
FT STRAND 182..191
FT /evidence="ECO:0007829|PDB:1AOE"
SQ SEQUENCE 192 AA; 22139 MW; D8E3BEAC1DCADB4C CRC64;
MSKPNVAIIV AALKPALGIG YKGKMPWRLR KEIRYFKDVT TRTTKPNTRN AVIMGRKTWE
SIPQKFRPLP DRLNIILSRS YENKIIDDNI IHASSIESSL NLVSDVERVF IIGGAEIYNE
LINNSLVSHL LITEIEHPSP ESIEMDTFLK FPLESWTKQP KSELQKFVGD TVLEDDIKEG
DFTYNYTLWT RK
