› 3g49

X-ray diffraction
2.5Å resolution

N-(Pyridin-2-yl) Arylsulfonamide Inhibitors of 11b-Hydroxysteroid Dehydrogenase Type 1: Discovery of PF-915275

Released:
DOI: 10.2210/pdb3g49/pdb
PDB entry 3g49 coloured by chain, front view.
PDB entry 3g49 coloured by chain, side view.
PDB entry 3g49 coloured by chain, top view.
Source organism: Cavia porcellus
Primary publication:
N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275.
Siu M, Johnson TO, Wang Y, Nair SK, Taylor WD, Cripps SJ, Matthews JJ, Edwards MP, Pauly TA, Ermolieff J, Castro A, Hosea NA, LaPaglia A, Fanjul AN, Vogel JE
Bioorg Med Chem Lett 19 3493-7 (2009)
PMID: 19473839

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-180271 (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: 277 amino acids
Theoretical weight: 30.45 KDa
Source organism: Cavia porcellus
Expression system: Escherichia coli
UniProt:
  • Canonical: Q6QLL4 (Residues: 24-300; Coverage: 92%)
Gene name: HSD11B1
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 3G4 2 x 3G4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-D
Spacegroup: P212121
Unit cell:
a: 78.207Å b: 83.599Å c: 179.202Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.191 0.189 0.225
Expression system: Escherichia coli

Quick links

Citations

4 review citations

11β-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.
Pereira et al. (2012)
3 more

3 mentions without citation

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