› 4ori

X-ray diffraction
1.5Å resolution

Rat dihydroorotate dehydrogenase bound with DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)

Released:
DOI: 10.2210/pdb4ori/pdb
PDB entry 4ori coloured by chain, front view.
PDB entry 4ori coloured by chain, side view.
PDB entry 4ori coloured by chain, top view.
Source organism: Rattus norvegicus
Primary publication:
Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.
Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA
J Med Chem 57 5381-94 (2014)
PMID: 24801997

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-179032 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydroorotate dehydrogenase (quinone), mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 372 amino acids
Theoretical weight: 40.41 KDa
Source organism: Rattus norvegicus
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: Q63707 (Residues: 32-395; Coverage: 92%)
Gene name: Dhodh
Sequence domains: Dihydroorotate dehydrogenase
Structure domains: Aldolase class I

Ligands and Environments


Cofactor: Ligand FMN 1 x FMN
2 bound ligands:
Ligand ORO 1 x ORO
Ligand 2V6 1 x 2V6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 19-ID
Spacegroup: C2
Unit cell:
a: 124.365Å b: 43.845Å c: 63.305Å
α: 90° β: 99.96° γ: 90°
R-values:
R R work R free
0.183 0.18 0.234
Expression system: Escherichia coli BL21

Quick links

Citations

8 review citations

Malaria medicines: a glass half full?
Wells et al. (2015)
7 more

2 mentions without citation

Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.
Deng et al. (2014)
1 more