Rational design of a selective covalent modifier of G protein βγ subunits.

ABSTRACT: G protein-coupled receptors transduce signals through heterotrimeric G protein Gα and Gβγ subunits, both of which interact with downstream effectors to regulate cell function. Gβγ signaling has been implicated in the pathophysiology of several diseases, suggesting that Gβγ could be an important pharmaceutical target. Previously, we used a combination of virtual and manual screening to find small molecules that bind to a protein-protein interaction "hot spot" on Gβγ and block regulation of physiological effectors. One of the most potent and effective compounds from this screen was selenocystamine. In this study, we investigated the mechanism of action of selenocystamine and found that selenocysteamine forms a covalent complex with Gβγ by a reversible redox mechanism. Mass spectrometry and s

SUBMITTER: Dessal AL 

PROVIDER: S-EPMC3014279 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature