› 5axq

X-ray diffraction
1.77Å resolution

Crystal structure of the catalytic domain of PDE10A complexed with highly potent and brain-penetrant PDE10A Inhibitor with 2-oxindole scaffold

Released:
DOI: 10.2210/pdb5axq/pdb
PDB entry 5axq coloured by chain, front view.
PDB entry 5axq coloured by chain, side view.
PDB entry 5axq coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design and synthesis of a novel 2-oxindole scaffold as a highly potent and brain-penetrant phosphodiesterase 10A inhibitor.
Yoshikawa M, Kamisaki H, Kunitomo J, Oki H, Kokubo H, Suzuki A, Ikemoto T, Nakashima K, Kamiguchi N, Harada A, Kimura H, Taniguchi T
Bioorg Med Chem 23 7138-49 (2015)
PMID: 26494583

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: 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

4 bound ligands:
Ligand MG 2 x MG
Ligand ZN 2 x ZN
Ligand 4LP 1 x 4LP
Ligand 4LK 1 x 4LK
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P212121
Unit cell:
a: 49.685Å b: 81.793Å c: 159.849Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.172 0.171 0.211
Expression system: Escherichia coli

Quick links

Citations

1 review citation

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