› 3tfq

X-ray diffraction
1.8Å resolution

Crystal structure of 11b-hsd1 double mutant (l262r, f278e) complexed with 8-{[(2-CYANOPYRIDIN-3-YL)METHYL]SULFANYL}-6-HYDROXY-3,4-DIHYDRO-1H-PYRANO[3,4-C]PYRIDINE-5-CARBONITRILE

Released:
DOI: 10.2210/pdb3tfq/pdb
PDB entry 3tfq coloured by chain, front view.
PDB entry 3tfq coloured by chain, side view.
PDB entry 3tfq coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11β-hydroxydehydrogenase 1 (11β-HSD1).
Wu SC, Yoon D, Chin J, van Kirk K, Seethala R, Golla R, He B, Harrity T, Kunselman LK, Morgan NN, Ponticiello RP, Taylor JR, Zebo R, Harper TW, Li W, Wang M, Zhang L, Sleczka BG, Nayeem A, Sheriff S, Camac DM, Morin PE, Everlof JG, Li YX, Ferraro CA, Kieltyka K, Shou W, Vath MB, Zvyaga TA, Gordon DA, Robl JA
Bioorg Med Chem Lett 21 6693-8 (2011)
PMID: 21983444

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
2 bound ligands:
Ligand 07M 4 x 07M
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 74.5Å b: 94Å c: 167.8Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.166 0.165 0.193
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 citation in other articles

Identification of novel 11β-HSD1 inhibitors by combined ligand- and structure-based virtual screening.
Lagos et al. (2014)
5 more

3 mentions without citation

FRAGSITE: A Fragment-Based Approach for Virtual Ligand Screening.
Zhou et al. (2021)
2 more