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• W2899928082 abstract "Caseinolytic protease P (ClpP) has emerged as a promising new target for antibacterial development. While ClpPs from single isoform expressing bacteria have been studied in detail, the function and regulation of systems with more than one ClpP homologue are still poorly understood. Herein, we present fundamental studies toward understanding the ClpP system in C. difficile, an anaerobic spore-forming pathogen that contains two chromosomally distant isoforms of ClpP. Examination of proteomic and genomic data suggest that ClpP1 is the primary isoform responsible for normal growth and virulence, but little is known about the function of ClpP2 or the context required for the formation of functional proteases. For the first time in a pathogenic bacterium, we demonstrate that both isoforms are capable of forming operative proteases. Interestingly, ClpP1 is the only homologue that possesses characteristic response to small molecule acyldepsipeptide activation. On the contrary, both ClpP1 and ClpP2 respond to cochaperone activation to degrade an ssrA-tagged substrate. These observations indicate that ClpP2 is less susceptible to acyldepsipeptide activation but retains the ability to interact with a known cochaperone. Homology models reveal no obvious characteristics that would allow one to predict less efficient acyldepsipeptide binding. The reported findings establish the uniqueness of the ClpP system in C. difficile, open new avenues of inquiry, and highlight the importance of more detailed structural, genetic, and biological characterization of the ClpP system in C. difficile." @default.
• W2899928082 created "2018-11-16" @default.
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• W2899928082 date "2018-11-09" @default.
• W2899928082 modified "2023-10-16" @default.
• W2899928082 title "<i>Clostridium difficile</i> ClpP Homologues are Capable of Uncoupled Activity and Exhibit Different Levels of Susceptibility to Acyldepsipeptide Modulation" @default.
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• W2899928082 doi "https://doi.org/10.1021/acsinfecdis.8b00199" @default.
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• W2899928082 hasPublicationYear "2018" @default.
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