Nature, 2003-09, Vol.425 (6953), p.98-102
2003
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- Autor(en) / Beteiligte
- Titel
- Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules
- Ist Teil von
- Nature, 2003-09, Vol.425 (6953), p.98-102
- Ort / Verlag
- London: Nature Publishing
- Erscheinungsjahr
- 2003
- Quelle
- EBSCOhost Psychology and Behavioral Sciences Collection
- Beschreibungen/Notizen
- Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature01914Titel-ID: cdi_proquest_miscellaneous_743482825
- Format
- –
- Schlagworte
- 3',5'-Cyclic-GMP Phosphodiesterases, Binding Sites, Biological and medical sciences, Carbolines - chemistry, Carbolines - metabolism, Cardiovascular system, Catalytic Domain, Cyclic Nucleotide Phosphodiesterases, Type 5, Humans, Hydrogen Bonding, Imidazoles - chemistry, Imidazoles - metabolism, Medical sciences, Models, Molecular, Molecular biology, Pharmacology. Drug treatments, Phosphoric Diester Hydrolases - chemistry, Phosphoric Diester Hydrolases - metabolism, Piperazines - chemistry, Piperazines - metabolism, Protein Conformation, Purines, Sildenafil Citrate, Sulfones, Tadalafil, Triazines, Vardenafil Dihydrochloride, Vasodilator agents. Cerebral vasodilators