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Function

PDE5 is an phosphodiesterase : this enzyme catalyzes the hydrolysis of cGMP into 5'GMP. CGMP is an usual second messager in cell transduction. PDE5 regulates its concentration by hydrolysis. If an inhibitor binds instead of cGMP, cGMP concentration increases and the stimulus continues. PDE5 inhibition is particulary used for erectile disfunction.

Human PDE5 is a PDE of class I.

Disease

Relevance

Structural highlights

PDE5 is a dimeric protein of about 270 amino acids long. The C terminal has the catalytic domain and two Zn2+ binding site and N temrinal is the regulatory domain which includes two the GAF domain a and b. There are thus plural allosteric binding site for cGMP in the Cterminal and the N terminal. cGAMP binds on Gap a allosteric site and promotes the phosphorylation of SER 92 of PKG. This phosphorylation increases the affinity betwezen cGMP and PDE5 : another cGMP binds to the Gapb which allows the activation of the catalytic site of PDE5.  :http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518390/)

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