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Functional Dynamics and Membrane Interactions of Human Cytochromes P450

This is a past event.

Friday, October 2 at 11:00am to 12:15pm

Virtual Event

Join us for a talk on "Functional Dynamics and Membrane Interactions of  Human Cytochromes P450" with Dr. John C. Hackett, associate professor, Virginia Commonwealth University Massey Cancer Center. The seminar will take place on Friday, Oct. 12, 11:00 a.m. via Zoom. Please email bsi@fiu.edu for Zoom link.

The cytochromes P450 (CYPs) catalyze a dazzling array of transformations in xenobiotic and endobiotic metabolism. The range of chemical reactions and the breadth of substrates transformed by CYPs are immense; however, the interplay of protein dynamics, ligand binding, and catalysis they use to achieve such flexibility remains poorly understood. They have adopted two human cytochrome P450 enzymes, aromatase (CYP19A1) and CYP3A4, as models to explore these important concepts. 19A1 is very selective for its substrates, catalyzes the synthesis of estrogens from androgens, and is an invaluable target of pharmacotherapy for estrogen-dependent cancers. Conversely CYP3A4 is very promiscuous, catalyzes the oxidation of more than 75% of drugs, and presents a significant challenge to the development of new therapeutics. This talk will provide an overview of the general aspects of CYP structure and function, the physiology CYP19A1, and the basis for CYP3A4 mediated adverse drug interactions. Like many mammalian P450s, CYP19A1 and CYP3A4 are associated with the membrane and little is known about how this interaction regulates their functions. He will summarize both their recent work and proposed future studies aimed at understanding the fundamental aspects of ligand binding and the functional dynamics of both enzymes embedded in nanoscale lipid bilayers (Nanodiscs). Finally, he will outline our path forward that we anticipate will end with the determination membrane-embedded CYP and CYP-redox partner complex structures using small-angle neutron scattering, small-angle x-ray scattering, and computational modeling.