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Dynamics and Mechanism of Cytochrome P450 Aromatase

Thursday, August 27 at 3:30pm to 4:30pm

Virtual Event

To attend this event, please email for the Zoom link.

Join us for a talk on "Dynamics and Mechanism of Cytochrome P450 Aromatase" with Dr. John C. Hackett, Associate Professor, VCU Massey Cancer Center.

This talk will provide an overview of general aspects of cytochrome P450 (CYP) structure and function. The aromatase CYP19A1 (19A1 hereafter) is studied for its role in steroidogenesis and adopted as a model to explore the important questions of protein dynamics, ligand binding, and catalysis.

First, Dr. Hackett will summarize the recent advancements in understanding the fascinating catalytic mechanism of 19A1, which has been debated for more than 50 years, including a summary of his theoretical contributions to this discussion. Second, he will summarize their recent work aimed at understanding the fundamental aspects of ligand binding and protein dynamics in 19A1 in a native-like membrane environment using nanoscale lipid bilayers, or Nanodiscs. Specifically, he will provide evidence that conformational selection is present in ligand binding to 19A1, describe remarkable differences in substrate and inhibitor-induced protein dynamics, and a mechanism for substrate capture from the membrane. Finally, he will outline their path forward to determine the most rigorous, experimentally derived picture of a membrane-embedded CYP using small-angle neutron scattering, small-angle x-ray scattering, and computational modeling.