“Spectroscopic Characterization of Unique Iron and Copper Active Sites in Biology”

Iron and copper ions are ubiquitous in nature and serve a variety of important biological functions. The first part of my talk will focus on oxoiron(V) species, which are fleeting intermediates proposed in some of the most difficult oxidative transformations in biology. Using a biomimetic analog, we employed resonance Raman, electron paramagnetic resonance and Mössbauer spectroscopies, combined with DFT computations to elucidate key structural and electronic properties of an oxoiron(V)-imido complex. Our analysis defines spectroscopic parameters characteristic of perferryl intermediates similar to those proposed in biology. Next, I will focus on the characterization of novel Cu/O2 intermediates in the reaction cycle of the Formylglycine Generating Enzyme (FGE), which plays an important role in both sulfatase activation as well as protein engineering. Using high-energy X-ray techniques, we have spectroscopically defined the unique copper active site with and without its functional substrate, and now have evidence for key intermediates along the O2-reaction pathway. These results reveal how FGE utilizes its mononuclear copper active site to activate O2, initiate reaction with substrate, and generate Cα-formylglycine product. Together these studies highlight how I’ve utilized complementary spectroscopic insights to elucidate the roles of novel intermediates in important biological processes.