› 9diz

X-ray diffraction
3.1Å resolution

Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM959 (6-cyclopropyl-2,4-dimethyl-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one)

Released:
DOI: 10.2210/pdb9diz/pdb
Model geometry
Fit model/data
PDB entry 9diz coloured by chain, front view.
PDB entry 9diz coloured by chain, side view.
PDB entry 9diz coloured by chain, top view.
Source organism: Plasmodium falciparum 3D7
Primary publication:
Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.
Nie Z, Bonnert R, Tsien J, Deng X, Higgs C, El Mazouni F, Zhang X, Li R, Ho N, Feher V, Paulsen J, Shackleford DM, Katneni K, Chen G, Ng ACF, McInerney M, Wang W, Saunders J, Collins D, Yan D, Li P, Campbell M, Patil R, Ghoshal A, Mondal P, Kundu A, Chittimalla R, Mahadeva M, Kokkonda S, White J, Das R, Mukherjee P, Angulo-Barturen I, Jiménez-Díaz MB, Malmstrom R, Lawrenz M, Rodriguez-Granillo A, Rathod PK, Tomchick DR, Palmer MJ, Laleu B, Qin T, Charman SA, Phillips MA
J Med Chem (2024)
PMID: 39710971

Function and Biology Details

Reaction catalysed: 
(S)-dihydroorotate + a quinone = orotate + a quinol
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned

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 Chain: A
Molecule details ›
Chain: A
Length: 401 amino acids
Theoretical weight: 45.39 KDa
Source organism: Plasmodium falciparum 3D7
Expression system: Escherichia coli
UniProt:
  • Canonical: Q08210 (Residues: 158-569; Coverage: 67%)
Gene name: PFF0160c
Sequence domains: Dihydroorotate dehydrogenase

Ligands and Environments


Cofactor: Ligand FMN 1 x FMN
2 bound ligands:
Ligand A1A53 1 x A1A53
Ligand OG6 1 x OG6
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: APS BEAMLINE 19-ID
Spacegroup: P64
Unit cell:
a: 85.224Å b: 85.224Å c: 139.888Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.198 0.194 0.228
Expression system: Escherichia coli

Quick links

Citations

1 mention without citation

Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.
Nie et al. (2025)