› 5c2h

X-ray diffraction
2.09Å resolution

PDE10 complexed with 6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-[3-(2-quinolyl)propoxy]pyrimidin-4-amine

Released:
DOI: 10.2210/pdb5c2h/pdb
PDB entry 5c2h coloured by chain, front view.
PDB entry 5c2h coloured by chain, side view.
PDB entry 5c2h coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis.
Shipe WD, Sharik SS, Barrow JC, McGaughey GB, Theberge CR, Uslaner JM, Yan Y, Renger JJ, Smith SM, Coleman PJ, Cox CD
J Med Chem 58 7888-94 (2015)
PMID: 26378882

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: 362 amino acids
Theoretical weight: 41.5 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y233 (Residues: 715-1055; Coverage: 32%)
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 4XU 1 x 4XU
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 49.657Å b: 81.28Å c: 157.101Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.209 0.207 0.24
Expression system: Escherichia coli

Quick links

Citations

6 citation in other articles

Fragment Hits: What do They Look Like and How do They Bind?
Giordanetto et al. (2019)
5 more

5 mentions without citation

Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia.
Layton et al. (2023)
4 more