› 4zo5

X-ray diffraction
2.5Å resolution

PDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dione

Released:
DOI: 10.2210/pdb4zo5/pdb
PDB entry 4zo5 coloured by chain, front view.
PDB entry 4zo5 coloured by chain, side view.
PDB entry 4zo5 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of [¹¹C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors.
Cox CD, Hostetler ED, Flores BA, Evelhoch JL, Fan H, Gantert L, Holahan M, Eng W, Joshi A, McGaughey G, Meng X, Purcell M, Raheem IT, Riffel K, Yan Y, Renger JJ, Smith SM, Coleman PJ
Bioorg Med Chem Lett 25 4893-4898 (2015)
PMID: 26077491

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:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-195089 (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: 323 amino acids
Theoretical weight: 37.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y233 (Residues: 715-1035; Coverage: 30%)
Gene name: PDE10A
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

4 bound ligands:
Ligand ZN 2 x ZN
Ligand MG 2 x MG
Ligand 4PX 1 x 4PX
Ligand 4Q0 1 x 4Q0
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P212121
Unit cell:
a: 51.07Å b: 81.38Å c: 159.18Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.241 0.238 0.285
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Phosphodiesterase 10 inhibitors in clinical development for CNS disorders.
Geerts et al. (2017)
1 more