[S11-4] Modulation of cytochrome c oxidase activity (CcO) is a novel therapeutic strategy
Cytochrome c oxidase (CcO) is the terminal enzyme of the mitochondrial electron transfer system. CcO couples the oxygen reducing reaction with the proton pumping. This reaction forms the proton gradient across the mitochondrial inner membrane, which is a driving force for ATP synthase. Recently, respiration and oxidative phosphorylation has become an attractive drug target. One such example is Bedaquiline, an ATP synthase inhibitor, a compound for Mycobacterium tuberculosis. When we screened small compounds that can modulate CcO activity, we identified some novel inhibitors of CcO and successfully determined CcO structures complexed with them. We also found that conservation of steric configuration around the heme among heme-containing proteins. That made us to hypothesize that we can specifically target the oxidases from pathogenic bacteria by using structural differences. I will introduce our recent data in the session.