A combination of solid-state NMR and MD simulations reveals the binding mode of a rhomboid protease inhibitor.

ABSTRACT: Intramembrane proteolysis plays a fundamental role in many biological and pathological processes. Intramembrane proteases thus represent promising pharmacological targets, but few selective inhibitors have been identified. This is in contrast to their soluble counterparts, which are inhibited by many common drugs, and is in part explained by the inherent difficulty to characterize the binding of drug-like molecules to membrane proteins at atomic resolution. Here, we investigated the binding of two different inhibitors to the bacterial rhomboid protease GlpG, an intramembrane protease characterized by a Ser-His catalytic dyad, using solid-state NMR spectroscopy. H/D exchange of deuterated GlpG can reveal the binding position while chemical shift perturbations additionally indicate the allos

SUBMITTER: Bohg C 

PROVIDER: S-EPMC8494044 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature