› 6k9u

X-ray diffraction
2.35Å resolution

Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Highly Selective PDE10A Inhibitor

Released:
DOI: 10.2210/pdb6k9u/pdb
PDB entry 6k9u coloured by chain, front view.
PDB entry 6k9u coloured by chain, side view.
PDB entry 6k9u coloured by chain, top view.
Source organism: Rattus norvegicus
Primary publication:
Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety.
Koizumi Y, Tanaka Y, Matsumura T, Kadoh Y, Miyoshi H, Hongu M, Takedomi K, Kotera J, Sasaki T, Taniguchi H, Watanabe Y, Takakuwa M, Kojima K, Baba N, Nakamura I, Kawanishi E
Bioorg Med Chem 27 3440-3450 (2019)
PMID: 31235264

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-193052 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Chain: A
Molecule details ›
Chain: A
Length: 311 amino acids
Theoretical weight: 35.91 KDa
Source organism: Rattus norvegicus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9QYJ6 (Residues: 463-770; Coverage: 39%)
Gene name: Pde10a
Sequence domains: 3'5'-cyclic nucleotide phosphodiesterase

Ligands and Environments

4 bound ligands:
Ligand ZN 1 x ZN
Ligand MG 1 x MG
Ligand D4L 1 x D4L
Ligand SO4 1 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: R3
Unit cell:
a: 120.456Å b: 120.456Å c: 83.899Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.177 0.175 0.215
Expression system: Spodoptera frugiperda

Quick links

Citations

1 review citation

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5-a]pyrimidine scaffold.
Hammouda et al. (2022)
2 other articles