@article{b9763e74081943ee80be124cf37f25d5,
title = "Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Small Molecule Activators of ClpP Protease",
abstract = "ClpP is a cylindrical serine protease whose ability to degrade proteins is regulated by the unfoldase ATP-dependent chaperones. ClpP on its own can only degrade small peptides. Here, we used ClpP as a target in a high-throughput screen for compounds, which activate the protease and allow it to degrade larger proteins, hence, abolishing the specificity arising from the ATP-dependent chaperones. Our screen resulted in five distinct compounds, which we designate as Activators of Self-Compartmentalizing Proteases 1 to 5 (ACP1 to 5). The compounds are found to stabilize the ClpP double-ring structure. The ACP1 chemical structure was considered to have drug-like characteristics and was further optimized to give analogs with bactericidal activity. Hence, the ACPs represent classes of compounds that can activate ClpP and that can be developed as potential novel antibiotics.",
author = "Elisa Leung and Alessandro Datti and Michele Cossette and Jordan Goodreid and McCaw, {Shannon E.} and Michelle Mah and Alina Nakhamchik and Koji Ogata and {El Bakkouri}, Majida and Cheng, {Yi Qiang} and Wodak, {Shoshana J.} and Eger, {Bryan T.} and Pai, {Emil F.} and Jun Liu and Scott Gray-Owen and Batey, {Robert A.} and Houry, {Walid A.}",
note = "Funding Information: This work was supported by the Canadian Institutes of Health Research Emerging Team Grants from the Institute of Infection and Immunity (XNE-86945) to A.D., E.F.P., J.L., S.G.-O., R.A.B., and W.A.H. M.E.B. is the recipient of a fellowship from the Canadian Institutes of Health Research (CIHR) Strategic Training Program in Protein Folding and Interaction Dynamics: Principles and Diseases. S.J.W. is Canada Research Chair Tier 1, funded by the Canada Institute of Health Research. ",
year = "2011",
month = sep,
day = "23",
doi = "10.1016/j.chembiol.2011.07.023",
language = "English",
volume = "18",
pages = "1167--1178",
journal = "Chemistry and Biology",
issn = "1074-5521",
publisher = "Elsevier Inc.",
number = "9",
}