› 7lrl

X-ray diffraction
2Å resolution

Co-complex CYP46A1 with 7742 (Soticlestat/TAK-935))

Released:
DOI: 10.2210/pdb7lrl/pdb
PDB entry 7lrl coloured by chain, front view.
PDB entry 7lrl coloured by chain, side view.
PDB entry 7lrl coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Soticlestat, a Potent and Selective Inhibitor for Cholesterol 24-Hydroxylase (CH24H).
Koike T, Yoshikawa M, Ando HK, Farnaby W, Nishi T, Watanabe E, Yano J, Miyamoto M, Kondo S, Ishii T, Kuroita T
J Med Chem 64 12228-12244 (2021)
PMID: 34387987

Function and Biology Details

Reaction catalysed: 
Cholesterol + [reduced NADPH--hemoprotein reductase] + O(2) = (24S)-cholest-5-ene-3-beta,24-diol + [oxidized NADPH--hemoprotein reductase] + H(2)O
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-195348 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cholesterol 24-hydroxylase Chain: A
Molecule details ›
Chain: A
Length: 474 amino acids
Theoretical weight: 54.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y6A2 (Residues: 28-494; Coverage: 93%)
Gene names: CYP46, CYP46A1
Sequence domains: Cytochrome P450

Ligands and Environments


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

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P212121
Unit cell:
a: 58.241Å b: 63.532Å c: 123.749Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.22 0.219 0.236
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes.
Wang et al. (2022)
1 more

2 mentions without citation

Assessment of cholesterol homeostasis in the living human brain.
Haider et al. (2022)
1 more