› 4ijw

X-ray diffraction
2.35Å resolution

Crystal structure of 11b-HSD1 double mutant (L262R, F278E) in complex with 3-[1-(4-chlorophenyl)cyclopropyl]-8-cyclopropyl[1,2,4]triazolo[4,3-a]pyridine

Released:
DOI: 10.2210/pdb4ijw/pdb
PDB entry 4ijw coloured by chain, front view.
PDB entry 4ijw coloured by chain, side view.
PDB entry 4ijw coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).
Li J, Kennedy LJ, Wang H, Li JJ, Walker SJ, Hong Z, O'Connor SP, Nayeem A, Camac DM, Morin PE, Sheriff S, Wang M, Harper T, Golla R, Seethala R, Harrity T, Ponticiello RP, Morgan NN, Taylor JR, Zebo R, Gordon DA, Robl JA
ACS Med Chem Lett 5 803-8 (2014)
PMID: 25050169

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: 10-10, 24-292; Coverage: 93%)
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 1EQ 4 x 1EQ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E
Spacegroup: P212121
Unit cell:
a: 74.5Å b: 94.3Å c: 167.4Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.205 0.205 0.238
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.
Liu et al. (2022)
12 other articles

1 mention without citation

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