› 8ewp

X-ray diffraction
2.4Å resolution

Crystal structure of CYP3A4 bound to an inhibitor

Released:
DOI: 10.2210/pdb8ewp/pdb
PDB entry 8ewp coloured by chain, front view.
PDB entry 8ewp coloured by chain, side view.
PDB entry 8ewp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Dynamic Ir(III) Photosensors for the Major Human Drug-Metabolizing Enzyme Cytochrome P450 3A4.
Denison M, Ahrens JJ, Dunbar MN, Warmahaye H, Majeed A, Turro C, Kocarek TA, Sevrioukova IF, Kodanko JJ
Inorg Chem 62 3305-3320 (2023)
PMID: 36758158

Function and Biology Details

Reactions catalysed: 
RH + [reduced NADPH--hemoprotein reductase] + O(2) = ROH + [oxidized NADPH--hemoprotein reductase] + H(2)O
Quinine + [reduced NADPH--hemoprotein reductase] + O(2) = 3-hydroxyquinine + [oxidized NADPH--hemoprotein reductase] + H(2)O
1,8-cineole + [reduced NADPH--hemoprotein reductase] + O(2) = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH--hemoprotein reductase] + H(2)O
Albendazole + [reduced NADPH--hemoprotein reductase] + O(2) = albendazole S-oxide + [oxidized NADPH--hemoprotein reductase] + H(2)O
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140290 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cytochrome P450 3A4 Chain: A
Molecule details ›
Chain: A
Length: 487 amino acids
Theoretical weight: 55.76 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P08684 (Residues: 21-503; Coverage: 96%)
Gene names: CYP3A3, CYP3A4
Sequence domains: Cytochrome P450

Ligands and Environments


Cofactor: Ligand HEM 1 x HEM
1 bound ligand:
Ligand X2Q 1 x X2Q
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL12-2
Spacegroup: I222
Unit cell:
a: 77.45Å b: 100.34Å c: 130.94Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.223 0.222 0.248
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Ruthenium-Based Photoactivated Chemotherapy.
Bonnet S. (2023)