Structural response of G protein binding to the cyclodepsipeptide inhibitor FR900359 probed by NMR spectroscopy.

ABSTRACT: The cyclodepsipeptide FR900359 (FR) and its analogs are able to selectively inhibit the class of G_q proteins by blocking GDP/GTP exchange. The inhibitor binding site of G_q has been characterized by X-ray crystallography, and various binding and functional studies have determined binding kinetics and mode of inhibition. Here we investigate isotope-labeled FR bound to the membrane-anchored G protein heterotrimer by solid-state nuclear magnetic resonance (ssNMR) and in solution by liquid-state NMR. The resulting data allowed us to identify regions of the inhibitor which show especially pronounced effects upon binding and revealed a generally rigid binding mode in the cis conformation under native-like conditions. The inclusion of the membrane environment allowed u

SUBMITTER: Bonifer C 

PROVIDER: S-EPMC11323312 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature