In Silico Screen Identifies a New Family of Agonists for the Bacterial Mechanosensitive Channel MscL.

ABSTRACT: MscL is a highly conserved mechanosensitive channel found in the majority of bacterial species, including pathogens. It functions as a biological emergency release valve, jettisoning solutes from the cytoplasm upon acute hypoosmotic stress. It opens the largest known gated pore and has been heralded as an antibacterial target. Although there are no known endogenous ligands, small compounds have recently been shown to specifically bind to and open the channel, leading to decreased cell growth and viability. Their binding site is at the cytoplasmic/membrane and subunit interfaces of the protein, which has been recently been proposed to play an essential role in channel gating. Here, we have targeted this pocket using in silico screening, resulting in the discovery of a new family of compound

SUBMITTER: Wray R 

PROVIDER: S-EPMC9030384 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature