› 3uuo

X-ray diffraction
2.11Å resolution

The discovery of potent, selectivity, and orally bioavailable pyrozoloquinolines as PDE10 inhibitors for the treatment of Schizophrenia

Released:
DOI: 10.2210/pdb3uuo/pdb
PDB entry 3uuo coloured by chain, front view.
PDB entry 3uuo coloured by chain, side view.
PDB entry 3uuo coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of Schizophrenia.
Ho GD, Yang SW, Smotryski J, Bercovici A, Nechuta T, Smith EM, McElroy W, Tan Z, Tulshian D, McKittrick B, Greenlee WJ, Hruza A, Xiao L, Rindgen D, Mullins D, Guzzi M, Zhang X, Bleickardt C, Hodgson R
Bioorg Med Chem Lett 22 1019-22 (2012)
PMID: 22222034

Function and Biology Details

Reaction catalysed: 
Nucleoside 3',5'-cyclic phosphate + H(2)O = nucleoside 5'-phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-195088 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Chains: A, B
Molecule details ›
Chains: A, B
Length: 337 amino acids
Theoretical weight: 39.01 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9Y233 (Residues: 708-714, 715-1036; Coverage: 31%)
Gene name: PDE10A
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

4 bound ligands:
Ligand 0CV 2 x 0CV
Ligand MG 2 x MG
Ligand ZN 2 x ZN
Ligand PO4 2 x PO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 50.566Å b: 82.231Å c: 161.34Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.196 0.195 0.227
Expression system: Spodoptera frugiperda

Quick links

Citations

4 review citations

Advances in Discovery of PDE10A Inhibitors for CNS-Related Disorders. Part 1: Overview of the Chemical and Biological Research.
Jankowska et al. (2019)
3 more

3 mentions without citation

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome.
Wang et al. (2015)
2 more