"The Redox Biology of Health and Energy: Understanding H+ and e– dynamics in enzymes that enable exotic non-equilibrium catalysis"


Prof. Brandon Greene
UCSB, Department of Chemistry and Biochemistry

Date and Location

Wednesday November 13, 2019 11:00am
1601 Elings Hall


Oxidoreductases, enzymes that catalyze oxidation/reduction reaction, represent 15-25% of annotated enzymes in a given genome and are essential for metabolism, biosynthesis, biomolecule repair, signaling, regulation, and managing reactive oxygen/nitrogen species. The requisite charge transport and redox catalysis in these enzymes requires proton-coupled electron transfer (PCET), and emergent function occurs when the largely quantum behavior of electrons couples to the largely classical behavior of the heavier proton. These emergent properties are leveraged by enzymes for efficient PCET and catalysis, yet the elements of protein structure that enable dynamic charge transport remain poorly understood. In this seminar I describe our recent studies on two oxidoreductases, [NiFe]-hydrogenase and ribonucleotide reductase, critical to microbial metabolism and de novo DNA biosynthesis respectively, that leverage complex enzyme scaffolds and dynamic amino acid and cofactor networks to support rapid and high fidelity PCET. By employing native and non-natural site directed mutagenesis in conjunction with time resolved spectroscopic techniques we resolve individual H+ and/or e– transfer events that provide us with unprecedented insight into biochemical PCET. The observations in these two distinct systems create an emergent picture of design principles for efficient charge transport, as well as providing a roadmap for rational drug design.