Delineation of molecular determinants for FR900359 inhibition of G_q/11 unlocks inhibition of Gα_s.

ABSTRACT: Heterotrimeric G proteins are essential mediators of intracellular signaling of G protein-coupled receptors. The G_q/11 subfamily consists of G_q, G₁₁, G₁₄, and G₁₆ proteins, of which all but G₁₆ are inhibited by the structurally related natural products YM-254890 and FR900359. These inhibitors act by preventing the GDP/GTP exchange, which is necessary for activation of all G proteins. A homologous putative binding site for YM-254890/FR900359 can also be found in members of the other three G protein families, G_s, G_i/o, and G_12/13, but none of the published analogs of YM-254890/FR900359 have shown any inhibitory activity for any of these. To explain why the YM-254890/FR900359 scaffold only inhib

SUBMITTER: Boesgaard MW 

PROVIDER: S-EPMC7535923 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature