Mechanistic Studies of Antibiotics Targeting Chaperone-Dependent Proteases in Bacteria

Much high-impact research in the chemical and biological sciences, particularly that which underlies innovations in medicine, began with curiosity about the structures and mechanisms of bioactive small molecules. In search of potentially transformative discoveries, my research group is focused on molecules that are anomalous by virtue of their structures and the mechanisms by which they perturb biological systems. The seminar will describe how our recent studies of such molecules have yielded new insights into the structures and functions of chaperone-dependent proteases that enable protein homoeostasis in bacteria. In particular, I will discuss antibiotics that either inhibit or activate the ClpP peptidase and that inhibit the 20S proteasome from Mycobacterium tuberculosis. I will also highlight how these studies are the bases of compelling leads for first-in-class anti-bacterial drugs.

Speaker: Jason Sello, UC San Francisco