› 3ch6

X-ray diffraction
2.35Å resolution

Crystal Structure of 11beta-HSD1 Double Mutant (L262R, F278E) Complexed with (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone

Released:
DOI: 10.2210/pdb3ch6/pdb
PDB entry 3ch6 coloured by chain, front view.
PDB entry 3ch6 coloured by chain, side view.
PDB entry 3ch6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.
Wang H, Ruan Z, Li JJ, Simpkins LM, Smirk RA, Wu SC, Hutchins RD, Nirschl DS, Van Kirk K, Cooper CB, Sutton JC, Ma Z, Golla R, Seethala R, Salyan ME, Nayeem A, Krystek SR, Sheriff S, Camac DM, Morin PE, Carpenter B, Robl JA, Zahler R, Gordon DA, Hamann LG
Bioorg Med Chem Lett 18 3168-72 (2008)
PMID: 18485702

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, D, E
Molecule details ›
Chains: A, B, D, E
Length: 286 amino acids
Theoretical weight: 31.35 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P28845 (Residues: 24-292; Coverage: 92%)
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 311 4 x 311
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P212121
Unit cell:
a: 74.5Å b: 94.3Å c: 167Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.194 0.187 0.23
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

11 citation in other articles

N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275.
Siu et al. (2009)
10 more

2 mentions without citation

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