› 6xz9

X-ray diffraction
2.77Å resolution

Structure of aldosterone synthase (CYP11B2) in complex with 5-chloro-3,3-dimethyl-2-[5-[1-(1-methylpyrazole-4-carbonyl)azetidin-3-yl]oxy-3-pyridyl]isoindolin-1-one

Released:
DOI: 10.2210/pdb6xz9/pdb
PDB entry 6xz9 coloured by chain, front view.
PDB entry 6xz9 coloured by chain, side view.
PDB entry 6xz9 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.
Liu Y, Wu J, Zhou M, Chen W, Li D, Wang Z, Hornsperger B, Aebi JD, Märki HP, Kuhn B, Wang L, Kuglstatter A, Benz J, Müller S, Hochstrasser R, Ottaviani G, Xin J, Kirchner S, Mohr S, Verry P, Riboulet W, Shen HC, Mayweg AV, Amrein K, Tan X
J Med Chem 63 6876-6897 (2020)
PMID: 32530624

Function and Biology Details

Reactions catalysed: 
A steroid + 2 reduced adrenodoxin + O(2) + 2 H(+) = an 11-beta-hydroxysteroid + 2 oxidized adrenodoxin + H(2)O
Corticosterone + 2 reduced adrenodoxin + O(2) + 2 H(+) = 18-hydroxycorticosterone + 2 oxidized adrenodoxin + H(2)O
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-148500 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cytochrome P450 11B2, mitochondrial Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 489 amino acids
Theoretical weight: 56.24 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P19099 (Residues: 28-503; Coverage: 95%)
Gene name: CYP11B2
Sequence domains: Cytochrome P450

Ligands and Environments


Cofactor: Ligand HEC 3 x HEC
1 bound ligand:
Ligand O4W 3 x O4W
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: I222
Unit cell:
a: 107.682Å b: 121.603Å c: 298.702Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.236 0.234 0.273
Expression system: Escherichia coli

Quick links

Citations

2 citation in other articles

Genetic variants in CYP11B1 influence the susceptibility to coronary heart disease.
Huang et al. (2022)
1 more

1 mention without citation

Exploring the mechanism of action of Hedyotis diffusa Willd on acne using network analysis.
Seo et al. (2023)