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Special Inorganic Chemistry Seminar – Dr. Alec Follmer

February 22, 2024 2:00 pm - 3:30 pm


Flyer: Dr. Alec Follmer Flyer

Title: Controlling C-H Bond Activation: Structural and Dynamic Regulation of Reactive Intermediates in Cytochrome P450 Catalysis

Abstract: From metabolism and detoxification to the biosynthesis of steroids and natural products, cytochromes P450 (P450s) are heme-containing enzymes that utilize O2 for the activation of C–H bonds and serve ubiquitous roles in nearly all biological systems. Their enzymatic activity, however, requires the formation of highly reactive intermediates within their active sites that can lead to the generation of potentially harmful reactive oxygen species and/or deleterious effects to the protein itself. Accordingly, many P450s have evolved structural and dynamic mechanisms to regulate their catalytic activity that involve complex rearrangements of their protein scaffolds. Despite a general understanding and appreciation of this regulation, the specific mechanisms and the extent to which they can be generalized remains unclear. Here, I will highlight several new key insights into how the reactivity of P450s is the controlled by allosteric interactions far from the active site that were discovered using a combination of structural, spectroscopic, and computational methods. Together these studies provide a new perspective on the importance that conformational dynamics play in the regulation of P450 activity.