Structural research and functional intervention of Caseinolytic protease P
Caseinolytic protease P(ClpP)is a highly conserved serine proteolytic enzyme,typically forming complexes with the AAA+superfamily ATPases as chaperone proteins to regulate protein homeostasis within cells.Chemical intervention of the biological function of ClpP protease,especially the development of small-molecule agonists on ClpP protease,has been demonstrated as effective strategies for the treatment of a variety of diseases.In recent years,our group has made significant progress on ClpP protease in structural biology and chemical biology.On one hand,we employed structural biology methods to elucidate the crystal structures of Staphylococcus aureus ClpP(SaClpP)in three different conformations.Additionally,a gain-of-function mutant of SaClpP has been identified,which enhanced the understanding of the mechanism on ClpP activation.On the other hand,our group has undertaken the research on chemical intervention of pathogenic bacteria and human mitochondrial ClpP by small molecule agonists.We have developed small-molecule ClpP agonists with diverse structural scaffolds,and achieved selective activation of ClpP protease function across different species.These advances have promoted the ClpP-targeted antibacterial and antitumor research.
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维普
