Context-specific inhibition of translation by oxazolidinone antibiotics
Presented by Prof. Danica Fujimori
Hosted by Prof. Gonzalez
Over 40% of clinically used antibiotics target bacterial ribosome. Linezolid, an oxazolidinone class antibiotic used for the treatment of Gram-positive infections, inhibits translation by binding to the peptidyl transferase center of the bacterial ribosome. While long considered a global inhibitor of translation, recent findings have shown that this antibiotic does not inhibit the formation of every peptide bonds, but rather acts is a context-dependent manner. This seminar will describe our biochemical and structural studies which revealed that nascent peptide contributes to the formation of linezolid’s binding site within the ribosome, explaining the basis for context specificity. Our ongoing investigations into physiological relevance of the unusual mode of action of linezolid, and efforts to design the next generation of oxazolidinone antibiotics based on our understanding of their activity will also be discussed.
Danica Galonić Fujimori is a professor of Cellular and Molecular Pharmacology and Pharmaceutical Chemistry, associate director of Quantitative Biosciences Institute and associate director of Chemistry and Chemical Biology graduate program at University of California in San Francisco. Organic chemist by graduate training (PhD, University of Illinois Urbana-Champaign, 2005) and mechanistic enzymologist by postdoctoral training (Harvard Medical School, 2008), her lab combines organic chemistry and biochemical reconstitution to investigate enzymatic mechanisms and regulatory roles of posttranslational and posttranscriptional modifications. Her work has been recognized by several awards including V Foundation Scholar award, NSF Career award, Searle Scholar, and WM Keck Medical Research Award.