Premium
Redox Regulation of G protein βγ Subunits
Author(s) -
Dessal Axel,
Smrcka Alan V
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.908.12
Subject(s) - dithiothreitol , protein subunit , chemistry , redox , small molecule , protein kinase a , peptide , enzyme , biochemistry , mechanism of action , g protein , biophysics , receptor , biology , in vitro , organic chemistry , gene
The βγ‐subunit of G protein (Gβγ) dissociates from the α‐subunit upon activation of G protein‐coupled receptors. Once free, Gβγ is able to regulate many target proteins, including phospholipase C β2 (PLCβ2), phosphoinositide 3‐kinase γ (PI3Kγ) and G protein‐coupled receptor kinase 2 (GRK2). Our group has used a combination of virtual and manual screening to find small molecules that inhibit the interaction between Gβγ and the aforementioned proteins with affinities in the high nM range. Recently, we discovered another set of compounds (some with heavy metals, Hg 2+ , Cu 2+ and Ag + in their structure) that binding of a Gβγ‐binding peptide (SIGK) in an enzyme‐linked immunosorbent assay (ELISA) at concentrations in the low nM range. The effect of these small molecules persists after washing them away, and it is both prevented and reversed by dithiothreitol (DTT). This suggests that these compounds act directly at Gβγ by a reversible redox mechanism. Investigation of the mechanism of action of these compounds may lead to uncovering mechanisms for Gβγ regulation by both natural and synthetic redox active molecules. This work was funded by National Institutes of Health GM060286