› 4cq8

X-ray diffraction
1.98Å resolution

Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) in complex with Genz-669178

Released:
DOI: 10.2210/pdb4cq8/pdb
PDB entry 4cq8 coloured by chain, front view.
PDB entry 4cq8 coloured by chain, side view.
PDB entry 4cq8 coloured by chain, top view.
Source organism: Plasmodium falciparum
Primary publication:
In vitro resistance selections for Plasmodium falciparum dihydroorotate dehydrogenase inhibitors give mutants with multiple point mutations in the drug-binding site and altered growth.
Ross LS, Gamo FJ, Lafuente-Monasterio MJ, Singh OM, Rowland P, Wiegand RC, Wirth DF
J Biol Chem 289 17980-95 (2014)
PMID: 24782313

Function and Biology Details

Reaction catalysed: 
(S)-dihydroorotate + a quinone = orotate + a quinol
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-170607 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydroorotate dehydrogenase (quinone), mitochondrial Chains: A, B
Molecule details ›
Chains: A, B
Length: 401 amino acids
Theoretical weight: 45.39 KDa
Source organism: Plasmodium falciparum
Expression system: Escherichia coli
UniProt:
  • Canonical: Q08210 (Residues: 158-569; Coverage: 67%)
Gene name: PFF0160c
Sequence domains: Dihydroorotate dehydrogenase
Structure domains: Aldolase class I

Ligands and Environments


Cofactor: Ligand FMN 2 x FMN
2 bound ligands:
Ligand ORO 2 x ORO
Ligand JBW 2 x JBW
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: C2
Unit cell:
a: 147.82Å b: 69.13Å c: 103.85Å
α: 90° β: 103.84° γ: 90°
R-values:
R R work R free
0.171 0.17 0.19
Expression system: Escherichia coli

Quick links

Citations

7 review citations

Defining the biology component of the drug discovery strategy for malaria eradication.
Leroy et al. (2014)
6 more

4 mentions without citation

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.
Ogungbe et al. (2016)
3 more