With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Sean Elliott of Boston University to study the protein dynamics and regulatory mechanisms of bacterial enzymes that detoxify hydrogen peroxide. A multi-disciplinary approach making use of protein electrochemistry, biochemistry and crystallography will be used to examine the molecular determinants that govern how a redox enzyme turns on or shuts down reactivity through pairing redox- and spin state- changes of heme cofactors to conformational changes in protein structure. Such studies can provide a molecular level understanding of redox-based mechanisms of the regulation of catalysis.
Enzymes are masters of transforming one molecule into another. In this way, bacterial enzymes called cytochrome c peroxidases (bCCPs) detoxify the reactive molecule hydrogen peroxide and transform it into harmless water. Enzymes such as bCCP often also master their own regulation, where they are turned either on or off. Understanding how enzymes regulate their own activity is a critical aspect of understanding how they can act as catalysts. Here, a wide range of biochemical, structural, spectroscopic, and electrochemical approaches will be brought to bear to understand the reactivity of "activatable" bCCP and elucidate the principles of what turns on (and off) their activity. The graduate and undergraduate students involved in these efforts will receive a multi-disciplinary training. This project will be integrated with continued mentoring efforts as students and the PI will develop and participate as leaders in an ongoing series of workshops in bioinorganic chemistry.
