› 4bb5

X-ray diffraction
2.2Å resolution

Free-Wilson and Structural Approaches to Co-optimising Human and Rodent Isoform Potency for 11b-Hydroxysteroid Dehydrogenase Type 1 11b-HSD1 Inhibitors

Released:
DOI: 10.2210/pdb4bb5/pdb
PDB entry 4bb5 coloured by chain, front view.
PDB entry 4bb5 coloured by chain, side view.
PDB entry 4bb5 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Free-Wilson and structural approaches to co-optimizing human and rodent isoform potency for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors.
Goldberg FW, Leach AG, Scott JS, Snelson WL, Groombridge SD, Donald CS, Bennett SN, Bodin C, Gutierrez PM, Gyte AC
J Med Chem 55 10652-61 (2012)
PMID: 23153367

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-151298 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
11-beta-hydroxysteroid dehydrogenase 1 Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 292 amino acids
Theoretical weight: 32.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P28845 (Residues: 1-292; Coverage: 100%)
Gene names: HSD11, HSD11B1, HSD11L, SDR26C1
Sequence domains: short chain dehydrogenase
Structure domains: NAD(P)-binding Rossmann-like Domain

Ligands and Environments


Cofactor: Ligand NAP 4 x NAP
1 bound ligand:
Ligand HD2 4 x HD2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P212121
Unit cell:
a: 48.781Å b: 132.482Å c: 154.819Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.184 0.182 0.22
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Designing novel building blocks is an overlooked strategy to improve compound quality.
Goldberg et al. (2015)
2 more

3 mentions without citation

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors.
Osman et al. (2021)
2 more