› 6q2t

X-ray diffraction
2.8Å resolution

Human sterol 14a-demethylase (CYP51) in complex with the functionally irreversible inhibitor (R)-N-(1-(3-chloro-4'-fluoro-[1,1'-biphenyl]-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-(3-fluoro-5-(5-fluoropyrimidin-4-yl)phenyl)-1,3,4-oxadiazol-2-yl)benzamide

Released:
DOI: 10.2210/pdb6q2t/pdb
PDB entry 6q2t coloured by chain, front view.
PDB entry 6q2t coloured by chain, side view.
PDB entry 6q2t coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Validation of Human Sterol 14α-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors.
Friggeri L, Hargrove TY, Wawrzak Z, Guengerich FP, Lepesheva GI
J Med Chem 62 10391-10401 (2019)
PMID: 31663733

Function and Biology Details

Reaction catalysed: 
(1a) a 14-alpha-methylsteroid + [reduced NADPH--hemoprotein reductase] + O(2) = a 14-alpha-hydroxysteroid + [oxidized NADPH--hemoprotein reductase] + H(2)O
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-172597 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Lanosterol 14-alpha demethylase Chains: A, B
Molecule details ›
Chains: A, B
Length: 446 amino acids
Theoretical weight: 51.05 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q16850 (Residues: 67-509; Coverage: 87%)
Gene names: CYP51, CYP51A1
Sequence domains: Cytochrome P450

Ligands and Environments

3 bound ligands:
Ligand HEM 2 x HEM
Ligand PJM 3 x PJM
Ligand DXC 8 x DXC
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-G
Spacegroup: I4
Unit cell:
a: 117.664Å b: 117.664Å c: 157.842Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.228 0.227 0.256
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases.
Monk et al. (2021)
2 more

3 mentions without citation

Validation of Human Sterol 14α-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors.
Friggeri et al. (2019)
2 more