› 5xkm

X-ray diffraction
2.16Å resolution

Crystal structure of human phosphodiesterase 2A in complex with 6-methyl-N-(1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Released:
DOI: 10.2210/pdb5xkm/pdb
PDB entry 5xkm coloured by chain, front view.
PDB entry 5xkm coloured by chain, side view.
PDB entry 5xkm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders.
Mikami S, Sasaki S, Asano Y, Ujikawa O, Fukumoto S, Nakashima K, Oki H, Kamiguchi N, Imada H, Iwashita H, Taniguchi T
J Med Chem 60 7658-7676 (2017)
PMID: 28759228

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-126261 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
cGMP-dependent 3',5'-cyclic phosphodiesterase Chains: A, B, C, D, E, F
Molecule details ›
Chains: A, B, C, D, E, F
Length: 345 amino acids
Theoretical weight: 40.23 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O00408 (Residues: 578-919; Coverage: 36%)
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 MG 8 x MG
Ligand ZN 6 x ZN
Ligand 87R 6 x 87R
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P1
Unit cell:
a: 72.925Å b: 89.768Å c: 90.361Å
α: 107.31° β: 113.85° γ: 89.84°
R-values:
R R work R free
0.205 0.202 0.256
Expression system: Spodoptera frugiperda

Quick links

Citations

4 review citations

Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.
Baillie et al. (2019)
3 more