› 5k9d

X-ray diffraction
1.7Å resolution

Crystal structure of human dihydroorotate dehydrogenase at 1.7 A resolution

Released:
DOI: 10.2210/pdb5k9d/pdb
PDB entry 5k9d coloured by chain, front view.
PDB entry 5k9d coloured by chain, side view.
PDB entry 5k9d coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.
Lewis TA, Sykes DB, Law JM, Muñoz B, Rustiguel JK, Nonato MC, Scadden DT, Schreiber SL
ACS Med Chem Lett 7 1112-1117 (2016)
PMID: 27994748

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: 368 amino acids
Theoretical weight: 39.94 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q02127 (Residues: 29-395; Coverage: 93%)
Gene name: DHODH
Sequence domains: Dihydroorotate dehydrogenase
Structure domains: Aldolase class I

Ligands and Environments


Cofactor: Ligand FNR 1 x FNR
6 bound ligands:
Ligand ORO 1 x ORO
Ligand CE9 1 x CE9
Ligand SO4 2 x SO4
Ligand ACT 3 x ACT
Ligand CL 3 x CL
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: LNLS BEAMLINE W01B-MX2
Spacegroup: P3221
Unit cell:
a: 90.14Å b: 90.14Å c: 122.152Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.138 0.136 0.16
Expression system: Escherichia coli

Quick links

Citations

6 review citations

Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine.
Wang et al. (2021)
5 more

2 mentions without citation

Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.
Lewis et al. (2016)
1 more