› 2chm

X-ray diffraction
1.6Å resolution

Crystal structure of N2 substituted pyrazolo pyrimidinones - a flipped binding mode in PDE5

Released:
DOI: 10.2210/pdb2chm/pdb
PDB entry 2chm coloured by chain, front view.
PDB entry 2chm coloured by chain, side view.
PDB entry 2chm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.
Allerton CM, Barber CG, Beaumont KC, Brown DG, Cole SM, Ellis D, Lane CA, Maw GN, Mount NM, Rawson DJ, Robinson CM, Street SD, Summerhill NW
J. Med. Chem. 49 3581-94 (2006)
PMID: 16759100

Function and Biology Details

Reactions catalysed: 
Guanosine 3',5'-cyclic phosphate + H(2)O = guanosine 5'-phosphate
Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:
Structure domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131207 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3',5'-cyclic-AMP phosphodiesterase 4B; cGMP-specific 3',5'-cyclic phosphodiesterase Chain: A
Molecule details ›
Chain: A
Length: 326 amino acids
Theoretical weight: 37.61 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: O76074 (Residues: 534-657, 683-858; Coverage: 34%)
  • Canonical: Q07343 (Residues: 451-476; Coverage: 4%)
Gene names: DPDE4, PDE4B, PDE5, PDE5A
Sequence domains: 3'5'-cyclic nucleotide phosphodiesterase
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

4 bound ligands:
Ligand ZN 1 x ZN
Ligand MG 1 x MG
Ligand 3P4 1 x 3P4
Ligand MES 1 x MES
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: C2
Unit cell:
a: 55.836Å b: 76.656Å c: 81.269Å
α: 90° β: 102.58° γ: 90°
R-values:
R R work R free
0.195 0.195 0.223
Expression system: Trichoplusia ni

Quick links

Citations

1 review citation

Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies.
Li et al. (2022)
3 other articles

1 mention without citation

[A systematic pharmacological investigation of pharmacologically active ingredients in Toujie Quwen granules for treatment of COVID-19].
Ma et al. (2020)