› 3hdz

X-ray diffraction
1.8Å resolution

Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors

Released:
DOI: 10.2210/pdb3hdz/pdb
PDB entry 3hdz coloured by chain, front view.
PDB entry 3hdz coloured by chain, side view.
PDB entry 3hdz coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors.
Owen DR, Walker JK, Jon Jacobsen E, Freskos JN, Hughes RO, Brown DL, Bell AS, Brown DG, Phillips C, Mischke BV, Molyneaux JM, Fobian YM, Heasley SE, Moon JB, Stallings WC, Joseph Rogier D, Fox DN, Palmer MJ, Ringer T, Rodriquez-Lens M, Cubbage JW, Blevis-Bal RM, Benson AG, Acker BA, Maddux TM, Tollefson MB, Bond BR, Macinnes A, Yu Y
Bioorg Med Chem Lett 19 4088-91 (2009)
PMID: 19540112

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 analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131204 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3',5'-cyclic-AMP phosphodiesterase 4A; cGMP-specific 3',5'-cyclic phosphodiesterase Chain: A
Molecule details ›
Chain: A
Length: 324 amino acids
Theoretical weight: 37.35 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O76074 (Residues: 536-657, 683-858; Coverage: 34%)
  • Canonical: P27815 (Residues: 478-503; Coverage: 3%)
Gene names: DPDE2, PDE4A, PDE5, PDE5A
Sequence domains: 3'5'-cyclic nucleotide phosphodiesterase
Structure domains: 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain

Ligands and Environments

3 bound ligands:
Ligand PD6 1 x PD6
Ligand ZN 1 x ZN
Ligand MG 1 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: C2
Unit cell:
a: 56.015Å b: 76.502Å c: 80.72Å
α: 90° β: 102.9° γ: 90°
R-values:
R R work R free
0.181 0.179 0.21
Expression system: Spodoptera frugiperda

Quick links

Citations

3 review citations

Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions.
Francis et al. (2011)
2 more

2 mentions without citation

Identification of a Novel 1,2,3,4-Tetrahydrobenzo[b][1,6]naphthyridine Analogue as a Potent Phosphodiesterase 5 Inhibitor with Improved Aqueous Solubility for the Treatment of Alzheimer's Disease.
Fiorito et al. (2017)
1 more