› 5mvd

X-ray diffraction
1.95Å resolution

Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds

Released:
DOI: 10.2210/pdb5mvd/pdb
PDB entry 5mvd coloured by chain, front view.
PDB entry 5mvd coloured by chain, side view.
PDB entry 5mvd coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds.
Sainas S, Pippione AC, Giorgis M, Lupino E, Goyal P, Ramondetti C, Buccinnà B, Piccinini M, Braga RC, Andrade CH, Andersson M, Moritzer AC, Friemann R, Mensa S, Al-Kadaraghi S, Boschi D, Lolli ML
Eur J Med Chem 129 287-302 (2017)
PMID: 28235702

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-169672 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydroorotate dehydrogenase (quinone), mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 363 amino acids
Theoretical weight: 39.5 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q02127 (Residues: 33-395; Coverage: 92%)
Gene name: DHODH
Sequence domains: Dihydroorotate dehydrogenase
Structure domains: Aldolase class I

Ligands and Environments


Cofactor: Ligand FMN 1 x FMN
4 bound ligands:
Ligand ORO 1 x ORO
Ligand U91 1 x U91
Ligand ACT 2 x ACT
Ligand CL 3 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-2
Spacegroup: P3221
Unit cell:
a: 90.85Å b: 90.85Å c: 122.924Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.169 0.167 0.202
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

13 citation in other articles

Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties.
Cao et al. (2019)
12 more

1 mention without citation

A comprehensive drug repurposing study for COVID19 treatment: novel putative dihydroorotate dehydrogenase inhibitors show association to serotonin-dopamine receptors.
Berber et al. (2021)