Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334). 3',5'-cyclic GMP + H2O = GMP + H(+) Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc. Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc. Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast. Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1. Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B. Phosphorylation is regulated by binding of cGMP to the two allosteric sites (By similarity). Phosphorylation by PRKG1 leads to its activation. Belongs to the cyclic nucleotide phosphodiesterase family. Was initially thought to act as a major regulator of cardiac hypertrophy in myocytes and muscle and investigations have been made on selective PDE5A inhibitors that could protect against cardiovascular disease. However, while PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signaling is often depressed by heart disease, limiting its effect. Moreover, clinical trial using PDE5A inhibitors were disappointing.