› 4d08

X-ray diffraction
1.9Å resolution

PDE2a catalytic domain in complex with a brain penetrant inhibitor

Released:
DOI: 10.2210/pdb4d08/pdb
PDB entry 4d08 coloured by chain, front view.
PDB entry 4d08 coloured by chain, side view.
PDB entry 4d08 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement.
Buijnsters P, De Angelis M, Langlois X, Rombouts FJ, Sanderson W, Tresadern G, Ritchie A, Trabanco AA, VanHoof G, Roosbroeck YV, Andrés JI
ACS Med Chem Lett 5 1049-53 (2014)
PMID: 25221665

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-517247 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
cGMP-dependent 3',5'-cyclic phosphodiesterase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 353 amino acids
Theoretical weight: 41.43 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O00408 (Residues: 578-921; Coverage: 37%)
Gene name: PDE2A
Sequence domains: 3'5'-cyclic nucleotide phosphodiesterase
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

3 bound ligands:
Ligand ZN 4 x ZN
Ligand Q2T 4 x Q2T
Ligand MG 4 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P1
Unit cell:
a: 56.04Å b: 74.15Å c: 92.77Å
α: 109.04° β: 91.73° γ: 91.34°
R-values:
R R work R free
0.215 0.213 0.247
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

Target engagement in lead generation.
Durham et al. (2015)
1 more

9 mentions without citation

Methanogen diversity evidenced by molecular characterization of methyl coenzyme M reductase A (mcrA) genes in hydrothermal sediments of the Guaymas Basin.
Dhillon et al. (2005)
8 more