Friday, February 22, 2019
Prof. Vincenzo Venditti
Department of Chemistry
Iowa State University
Reception: 3:00PM Hand 1135
Seminar: 3:30PM Hand 1144
Protein conformational transitions are fundamental to signaling, enzyme catalysis, and assembly of cellular structures. Understanding how the interconversion among different folded structures affects function is a grand challenge in biology and meeting this challenge will have an impact in treating a large number of diseases that are linked to signaling cascades or enzymes. In the past decade, NMR spectroscopy, in concert with other structural methods, has helped to realize how conformational dynamics assist protein function. However, these studies have been largely limited to low molecular weight systems. Enzymes are typically large oligomeric proteins with complex molecular features and their function is often controlled by long-range communication between distant sites (often located on different structural domains) mediated by substrate/cofactor binding. Therefore, there is a critical need to increase our understanding of how modulation of the “local” conformational dynamics upon ligand binding propagates into large-scale interdomain rearrangements and, ultimately, determines the function of complex multidomain proteins. In my laboratory we investigate how conformational dynamics mediate self-regulation of large multidomain enzymes. The systems of interest in my group are Enzyme I (EI) of the bacterial phosphotransferase system (PTS), and the human RNA demethylases FTO and Alkbh5. Our ultimate goal is to identify novel strategies guided by atomic resolution insight in enzyme conformational changes to selectively target these proteins with small molecules that inhibit bacterial infections and cancer progression.
Building upon our biophysical work, we are also interested in investigating the role played by molecular dynamics at the catalyst/solution interface in regulation of nanoparticle catalysts. We have developed a suite of NMR experiments and sample preparation protocols to obtain a comprehensive description of the structures, kinetics, and thermodynamics underlaying adsorption/desorption equilibria. We are currently employing this approach to investigate the phenol hydrogenation reaction catalyzed by Pd/ceria nanoparticles.
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