 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.