› 4zgx

X-ray diffraction
3.2Å resolution

Structure of aldosterone synthase (CYP11B2) in complex with (+)-(R)-N-(4-(4-chloro-3-fluorophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide

Released:
DOI: 10.2210/pdb4zgx/pdb
PDB entry 4zgx coloured by chain, front view.
PDB entry 4zgx coloured by chain, side view.
PDB entry 4zgx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors: In Vivo Evaluation in Rodents and Cynomolgus Monkeys.
Martin RE, Aebi JD, Hornsperger B, Krebs HJ, Kuhn B, Kuglstatter A, Alker AM, Märki HP, Müller S, Burger D, Ottaviani G, Riboulet W, Verry P, Tan X, Amrein K, Mayweg AV
J Med Chem 58 8054-65 (2015)
PMID: 26403853

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:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-148499 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cytochrome P450 11B2, mitochondrial Chains: A, B, C, D, E, F, G, H, I, J, K, L
Molecule details ›
Chains: A, B, C, D, E, F, G, H, I, J, K, L
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
Structure domains: Cytochrome P450

Ligands and Environments


Cofactor: Ligand HEM 12 x HEM
1 bound ligand:
Ligand QHC 10 x QHC
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P1
Unit cell:
a: 104.7Å b: 125.96Å c: 155.23Å
α: 70.25° β: 85.87° γ: 73.84°
R-values:
R R work R free
0.214 0.212 0.255
Expression system: Escherichia coli

Quick links

Citations

2 review citations

The potential of targeting CYP11B.
Bernhardt R. (2016)
1 more

5 mentions without citation

Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.
Rendic et al. (2018)
4 more