Feb 20
Chemistry Department Seminar: Ryan Steed, UNC Asheville
Associate Professor of Biochemistry, University of North Carolina Asheville
"Diversity and Vulnerability in Bacterial ATP Synthesis"
ATP is the universal energy currency of known life, and most of it is made by ATP synthases in the process of oxidative phosphorylation. F1Fo ATP synthase catalyzes the final step of this process in bacteria, mitochondria, and chloroplasts by using an electrochemical gradient of H+ to drive a rotary mechanism that condenses ADP and phosphate into ATP. While much is understood about this mechanism, we do not have a complete understanding of how H+ moves through the membrane-embedded Fo motor during ATP synthesis or during ATP-powered H+ pumping. Using cryo-electron microscopy and extensive mutagenesis of enzymes from E. coli and Pseudomonas aeruginosa (PA), we found unexpected differences in the H+ channels and revealed new roles for amino acid residues in the rotor-stator interface. Understanding the distinct features of these enzymes reveal vulnerabilities that can be exploited for antibiotic development. PA and Acinetobacter baumannii are Gram-negative bacteria identified as particular threats to public health, and both require ATP synthase for survival. We have synthesized a library of >150 compounds targeting the rotor-stator interface of ATP synthase, some of which show promising antibacterial activity.
**This seminar counts towards the chemistry major seminar attendance requirement.