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cGMP-specific phosphodiesterase type 5 is an enzyme () from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system. The ''phosphodiesterase (PDE)'' isozymes, found in several tissues including the rod and cone photoreceptor cells of the retina, belong to a large family of cyclic nucleotide PDEs that catalyze cAMP and cGMP hydrolysis. The interest in PDEs as molecular targets of drug action has grown with the development of isozyme-selective PDE inhibitors that offer potent inhibition of selected isozymes without the side-effects attributed to nonselective inhibitors such as theophylline. Sildenafil, vardenafil, and tadalafil are PDE5 inhibitors that are significantly more potent and selective than zaprinast and other early PDE5 inhibitors. == Action of PDE5 == PDE5 is an enzyme that accepts cGMP and breaks it down. Sildenafil, vardenafil and tadalafil are inhibitors of this enzyme, which bind to the catalytic site of PDE5. Both inhibitors bind with high affinity and specificity, and cGMP-binding to the allosteric sites stimulates binding of PDE5 inhibitors at the catalytic site. The kinetics of inhibitor binding and inhibition of catalysis imply the existence of two PDE5 conformers, and results of native gel electrophoresis reveal that PDE5 exists in two apparently distinct conformations, i.e., an extended conformer and a more compact conformer. PDE5 activity is modulated by a rapidly reversible redox switch. Chemical reduction of PDE5 relieves autoinhibition of enzyme functions; allosteric cGMP-binding activity is increased 10-fold, and catalytic activity is increased ~3-fold. The redox effect on allosteric cGMP-binding occurs in the isolated regulatory domain. A change in the state of reduction of PDE5 or the isolated regulatory domain is associated with an apparent conformational change similar to that caused by phosphorylation. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「CGMP-specific phosphodiesterase type 5」の詳細全文を読む スポンサード リンク
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