› 3wym

X-ray diffraction
2Å resolution

Crystal structure of the catalytic domain of PDE10A complexed with 1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Released:
DOI: 10.2210/pdb3wym/pdb
PDB entry 3wym coloured by chain, front view.
PDB entry 3wym coloured by chain, side view.
PDB entry 3wym coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor.
Kunitomo J, Yoshikawa M, Fushimi M, Kawada A, Quinn JF, Oki H, Kokubo H, Kondo M, Nakashima K, Kamiguchi N, Suzuki K, Kimura H, Taniguchi T
J Med Chem 57 9627-43 (2014)
PMID: 25384088

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

Assemblies composition:
homo dimer
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: 338 amino acids
Theoretical weight: 38.89 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y233 (Residues: 718-1055; Coverage: 32%)
Gene name: PDE10A
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

3 bound ligands:
Ligand MG 2 x MG
Ligand ZN 2 x ZN
Ligand 3K9 2 x 3K9
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P212121
Unit cell:
a: 49.701Å b: 81.707Å c: 161.533Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.18 0.179 0.215
Expression system: Escherichia coli

Quick links

Citations

6 review citations

Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery.
Hollas et al. (2019)
5 more