› 1ia4

X-ray diffraction
1.85Å resolution

Candida albicans dihydrofolate reductase complex in which the dihydronicotinamide moiety of dihydro-nicotinamide-adenine-dinucleotide phosphate (NADPH) is displaced by 5-{[4-(4-MORPHOLINYL)PHENYL]SULFANYL}-2,4-QUINAZOLINEDIAMIN (GW2021)

Released:
DOI: 10.2210/pdb1ia4/pdb
PDB entry 1ia4 coloured by chain, front view.
PDB entry 1ia4 coloured by chain, side view.
PDB entry 1ia4 coloured by chain, top view.
Source organism: Candida albicans
Primary publication:
X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.
Whitlow M, Howard AJ, Stewart D, Hardman KD, Chan JH, Baccanari DP, Tansik RL, Hong JS, Kuyper LF
J Med Chem 44 2928-32 (2001)
PMID: 11520201

Function and Biology Details

Reaction catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:
Structure domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-149838 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chains: A, B
Molecule details ›
Chains: A, B
Length: 192 amino acids
Theoretical weight: 22.19 KDa
Source organism: Candida albicans
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P22906 (Residues: 1-192; Coverage: 100%)
Gene name: DFR1
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
2 bound ligands:
Ligand TQ6 2 x TQ6
Ligand MES 2 x MES
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ELLIOTT GX-21
Spacegroup: P21
Unit cell:
a: 77.05Å b: 67.09Å c: 38.54Å
α: 90° β: 93.43° γ: 90°
R-values:
R R work R free
0.159 0.159 not available
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Antimicrobial dihydrofolate reductase inhibitors--achievements and future options: review.
Then RL. (2004)
17 other articles

1 mention without citation

Crystal structures of Candida albicans dihydrofolate reductase bound to propargyl-linked antifolates reveal the flexibility of active site loop residues critical for ligand potency and selectivity.
Paulsen et al. (2011)