› 6fmd

X-ray diffraction
1.58Å resolution

Targeting myeloid differentiation using potent human dihydroorotate dehydrogenase (hDHODH) inhibitors based on 2-hydroxypyrazolo[1,5-a]pyridine scaffold

Released:
DOI: 10.2210/pdb6fmd/pdb
PDB entry 6fmd coloured by chain, front view.
PDB entry 6fmd coloured by chain, side view.
PDB entry 6fmd coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors.
Sainas S, Pippione AC, Lupino E, Giorgis M, Circosta P, Gaidano V, Goyal P, Bonanni D, Rolando B, Cignetti A, Ducime A, Andersson M, Järvå M, Friemann R, Piccinini M, Ramondetti C, Buccinnà B, Al-Karadaghi S, Boschi D, Saglio G, Lolli ML
J Med Chem 61 6034-6055 (2018)
PMID: 29939742

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: 395 amino acids
Theoretical weight: 42.93 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q02127 (Residues: 1-395; Coverage: 100%)
Gene name: DHODH
Sequence domains: Dihydroorotate dehydrogenase
Structure domains: Aldolase class I

Ligands and Environments


Cofactor: Ligand FMN 1 x FMN
6 bound ligands:
Ligand DUH 1 x DUH
Ligand CL 2 x CL
Ligand ACT 6 x ACT
Ligand ORO 1 x ORO
Ligand GOL 4 x GOL
Ligand PGE 6 x PGE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P3221
Unit cell:
a: 90.441Å b: 90.441Å c: 122.446Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.138 0.137 0.16
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

5 review citations

DHODH and cancer: promising prospects to be explored.
Zhou et al. (2021)
4 more

5 mentions without citation

Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold: SAR of the Biphenyl Moiety.
Sainas et al. (2021)
4 more