Novel MscL agonists that allow multiple antibiotics cytoplasmic access activate the channel through a common binding site

• DOI: 10.1371/journal.pone.0228153
• Publication Date: 2020-01-24T18:48:41Z
• Authors: Robin Wray; Junmei Wang; Irene Iscla; Paul Blount
• Keywords: Spheroplast

The antibiotic resistance crisis is becoming dire, yet in the past several years few potential antibiotics or adjuvants with novel modes of action have been identified. bacterial mechanosensitive channel large conductance, MscL, found majority species, including pathogens, normally functions as an emergency release valve, sensing membrane tension upon low-osmotic stress and discharging cytoplasmic solutes before cell lysis. Opening huge ~30Å diameter pore MscL inappropriately detrimental to cell, allowing from even passage drugs into cytoplasm. Thus, a drug target. However, there are no known natural agonists, small compounds that modulate activity just now being Here we describe compound, K05, specifically modulates compare results those obtained for recently characterized agonist 011A. While structure K05 only vaguely resembles 011A, many findings, binding pocket, similar. On other hand, both vivo molecular dynamic simulations indicate two significantly different ways.