The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PDE5A  -  phosphodiesterase 5A, cGMP-specific

Bos taurus

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PDE5A

  • A fully functional chimeric PDE6alpha'/PDE5 enzyme containing the PDE6alpha' noncatalytic cGMP-binding sites, and the PDE5 catalytic domain has been efficiently expressed in the baculovirus/High Five cell system [1].
  • This PDE5-dependent ANP resistance may represent an important contributor to the sodium retention of liver disease [2].

High impact information on PDE5A


Biological context of PDE5A

  • Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation [7].
  • A deletion mutant of cGMP-binding cGMP-specific PDE (PDE5), encoding the 357 carboxyl-terminal amino acids including the catalytic domain, has been generated, expressed, and purified [5].
  • The regulatory domain of the cGMP-binding cGMP-specific 3':5'-cyclic nucleotide phosphodiesterase (PDE5) contains two homologous segments of amino acid sequence that encode allosteric cyclic nucleotide-binding sites, referred to as site a and site b, which are highly selective for cGMP over cAMP [6].
  • Sildenafil (Viagra), a specific PDE5 inhibitor, promotes penile erection by blocking the activity of PDE5, which causes cGMP to accumulate in the corpus cavernosum [8].
  • The results indicate that cGMP bound to allosteric cGMP-binding sites of PKG is protected from hydrolysis by PDE5 and that persistent protection of cGMP by either non-phosphorylated or autophosphorylated PKGs may be a positive-feedback control to sustain cGMP signalling [9].

Anatomical context of PDE5A

  • Chimeric cGMP phosphodiesterases (PDEs) have been constructed using components of the cGMP-binding PDE (PDE5) and cone photoreceptor phosphodiesterase (PDE6alpha') in order to study structure and function of the photoreceptor enzyme [1].
  • The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis [8].
  • Hybridization on total RNA extracted from dibutyryl-cAMP-treated NG108-15 cells shows a 5-fold increase of PDE5 9 kb mRNA: such an increase is not observed in N18TG2 although we observed a similar increase in the enzymatic activity of both cell lines [10].
  • Primary cultures of bovine aortic endothelial cells (BAEC) express cyclic nucleotide phosphodiesterase (CN PDE) isozymes of the PDE2, PDE4 and PDE5 gene families [11].
  • The increase in recombinant PDE5 catalytic activity brought about by phosphorylation was time-dependent and was obtained with 0.2-0.5 microM PKG subunit, which is approximately the cellular level of this enzyme in vascular smooth muscle [12].

Associations of PDE5A with chemical compounds


Analytical, diagnostic and therapeutic context of PDE5A


  1. Probing domain functions of chimeric PDE6alpha'/PDE5 cGMP-phosphodiesterase. Granovsky, A.E., Natochin, M., McEntaffer, R.L., Haik, T.L., Francis, S.H., Corbin, J.D., Artemyev, N.O. J. Biol. Chem. (1998) [Pubmed]
  2. Increased cGMP phosphodiesterase activity mediates renal resistance to ANP in rats with bile duct ligation. Ni, X.P., Safai, M., Gardner, D.G., Humphreys, M.H. Kidney Int. (2001) [Pubmed]
  3. Ectopic expression of bovine type 5 phosphodiesterase confers a renal phenotype in Drosophila. Broderick, K.E., Kean, L., Dow, J.A., Pyne, N.J., Davies, S.A. J. Biol. Chem. (2004) [Pubmed]
  4. The GAFa domains of rod cGMP-phosphodiesterase 6 determine the selectivity of the enzyme dimerization. Muradov, K.G., Boyd, K.K., Martinez, S.E., Beavo, J.A., Artemyev, N.O. J. Biol. Chem. (2003) [Pubmed]
  5. Expression of an active, monomeric catalytic domain of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). Fink, T.L., Francis, S.H., Beasley, A., Grimes, K.A., Corbin, J.D. J. Biol. Chem. (1999) [Pubmed]
  6. Studies of the molecular mechanism of discrimination between cGMP and cAMP in the allosteric sites of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). Turko, I.V., Francis, S.H., Corbin, J.D. J. Biol. Chem. (1999) [Pubmed]
  7. Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation. Turko, I.V., Francis, S.H., Corbin, J.D. Biochem. J. (1998) [Pubmed]
  8. Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. Turko, I.V., Ballard, S.A., Francis, S.H., Corbin, J.D. Mol. Pharmacol. (1999) [Pubmed]
  9. cGMP-dependent protein kinase protects cGMP from hydrolysis by phosphodiesterase-5. Kotera, J., Grimes, K.A., Corbin, J.D., Francis, S.H. Biochem. J. (2003) [Pubmed]
  10. cAMP-dependent induction of PDE5 expression in murine neuroblastoma cell differentiation. Giordano, D., Giorgi, M., Sette, C., Biagioni, S., Augusti-Tocco, G. FEBS Lett. (1999) [Pubmed]
  11. Altered expression of cyclic nucleotide phosphodiesterase isozymes during culture of aortic endothelial cells. Ashikaga, T., Strada, S.J., Thompson, W.J. Biochem. Pharmacol. (1997) [Pubmed]
  12. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Corbin, J.D., Turko, I.V., Beasley, A., Francis, S.H. Eur. J. Biochem. (2000) [Pubmed]
  13. Antimitogenic actions of organic nitrates are potentiated by sildenafil and mediated via activation of protein kinase A. Osinski, M.T., Rauch, B.H., Schrör, K. Mol. Pharmacol. (2001) [Pubmed]
  14. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues. Daugan, A., Grondin, P., Ruault, C., Le Monnier de Gouville, A.C., Coste, H., Linget, J.M., Kirilovsky, J., Hyafil, F., Labaudinière, R. J. Med. Chem. (2003) [Pubmed]
  15. Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle. Murthy, K.S. Biochem. J. (2001) [Pubmed]
  16. A photoaffinity probe covalently modifies the catalytic site of the cGMP-binding cGMP-specific phosphodiesterase (PDE-5). Corbin, J.D., Beasley, A., Turko, I.V., Haik, T.L., Mangum, K.A., Wells, J.N., Francis, S.H., Sekhar, K.R. Cell Biochem. Biophys. (1998) [Pubmed]
WikiGenes - Universities