Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions.

ABSTRACT: The activity of many proteins orchestrating different biological processes is regulated by allostery, where ligand binding at one site alters the function of another site. Allosteric changes can be brought about by either a change in the dynamics of a protein, or alteration in its mean structure. We have investigated the mechanisms of allostery induced by chemically distinct ligands in the cGMP-binding, cGMP-specific phosphodiesterase, PDE5. PDE5 is the target for catalytic site inhibitors, such as sildenafil, that are used for the treatment of erectile dysfunction and pulmonary hypertension. PDE5 is a multidomain protein and contains two N-terminal cGMP-specific phosphodiesterase, bacterial adenylyl cyclase, FhLA transcriptional regulator (GAF) domains, and a C-terminal catalytic domain.

SUBMITTER: Biswas KH 

PROVIDER: S-EPMC3048737 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature