› 3gmd

X-ray diffraction
2.28Å resolution

Structure-based design of 7-Azaindole-pyrrolidines as inhibitors of 11beta-Hydroxysteroid-Dehydrogenase type I

Released:
DOI: 10.2210/pdb3gmd/pdb
PDB entry 3gmd coloured by chain, front view.
PDB entry 3gmd coloured by chain, side view.
PDB entry 3gmd coloured by chain, top view.
Source organism: Mus musculus
Primary publication:
Structure-based design of 7-azaindole-pyrrolidine amides as inhibitors of 11β-hydroxysteroid dehydrogenase type I.
Valeur E, Christmann-Franck S, Lepifre F, Carniato D, Cravo D, Charon C, Bozec S, Musil D, Hillertz P, Doare L, Schmidlin F, Lecomte M, Schultz M, Roche D
Bioorg Med Chem Lett 22 5909-14 (2012)
PMID: 22901389

Function and Biology Details

Reactions catalysed: 
An 11-beta-hydroxysteroid + NADP(+) = an 11-oxosteroid + NADPH
A 7-beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-156141 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
11-beta-hydroxysteroid dehydrogenase 1 Chains: A, B, C, D, E, F, G, H
Molecule details ›
Chains: A, B, C, D, E, F, G, H
Length: 264 amino acids
Theoretical weight: 28.98 KDa
Source organism: Mus musculus
Expression system: Escherichia coli
UniProt:
  • Canonical: P50172 (Residues: 26-289; Coverage: 90%)
Gene names: Hsd11, Hsd11b1
Sequence domains: short chain dehydrogenase
Structure domains: NAD(P)-binding Rossmann-like Domain

Ligands and Environments


Cofactor: Ligand NDP 8 x NDP
2 bound ligands:
Ligand 2M3 8 x 2M3
Ligand SO4 9 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P21
Unit cell:
a: 127.336Å b: 70.486Å c: 132.956Å
α: 90° β: 91.78° γ: 90°
R-values:
R R work R free
0.27 0.252 0.306
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Modern advances in heterocyclic chemistry in drug discovery.
Taylor et al. (2016)
1 more

1 mention without citation

Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery.
Thomas et al. (2011)