@article{c0755db641244bf99251b0eb2f30be1a,
title = "Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: A model for the ClpX/ClpA-bound state of ClpP",
abstract = "In ClpXP and ClpAP complexes, ClpA and ClpX use the energy of ATP hydrolysis to unfold proteins and translocate them into the self- compartmentalized ClpP protease. ClpP requires the ATPases to degrade folded or unfolded substrates, but binding of acyldepsipeptide antibiotics (ADEPs) to ClpP bypasses this requirement with unfolded proteins. We present the crystal structure of Escherichia coli ClpP bound to ADEP1 and report the structural changes underlying ClpP activation. ADEP1 binds in the hydrophobic groove that serves as the primary docking site for ClpP ATPases. Binding of ADEP1 locks the N-terminal loops of ClpP in a β-hairpin conformation, generating a stable pore through which extended polypeptides can be threaded. This structure serves as a model for ClpP in the holoenzyme ClpAP and ClpXP complexes and provides critical information to further develop this class of antibiotics.",
author = "Li, {Dominic Him Shun} and Chung, {Yu Seon} and Melanie Gloyd and Ebenezer Joseph and Rodolfo Ghirlando and Wright, {Gerard D.} and Cheng, {Yi Qiang} and Maurizi, {Michael R.} and Alba Guarn{\'e} and Joaquin Ortega",
note = "Funding Information: We are grateful to Walid A. Houry for providing the pT9a-ClpP plasmid. We are in debt with M. Junop and the staff at the X25 beam line (BNL, NSLS) for assistance during data collection. This work was supported by a grant from the Canadian Institutes of Health Research to J.O. (MOP-82930) and G.D.W. (MT-14981), by a Canada Research Chair in Antibiotic Biochemistry (to G.D.W.) and an Early Researcher Award to A.G. (Ontario Ministry of Research Innovation). J.O. and A.G. are supported by the New Investigators program from CIHR. This work was also supported by the intramural research program of the Center for Cancer Research, NCI (M.R.M. and E.J.) and the National Institute of Diabetes and Digestive and Kidney Diseases (R.G.), NIH, Bethesda, MD. ",
year = "2010",
month = sep,
day = "24",
doi = "10.1016/j.chembiol.2010.07.008",
language = "English",
volume = "17",
pages = "959--969",
journal = "Chemistry and Biology",
issn = "1074-5521",
publisher = "Elsevier Inc.",
number = "9",
}