The following seminar will only be available remotely.
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Gianluigi Veglia, Professor, Biochemistry, Molecular Biology & Biophysics, University of Minnesota, MN, "An NMR View of the Functional and Dysfunctional States of Protein Kinase A in Health and Disease"

ABSTRACT

Protein kinase A is a prototypical and ubiquitous phosphoryl transferase involved in a plethora of cell processes, including memory, muscle contractility, and cell proliferation. Recent studies have revealed single-site mutations or gene fusions lead to aberrant kinases that are responsible for specific diseases such as Cushing’ syndrome and fibrolamellar hepatocellular carcinoma. Using NMR lenses, we discovered that conformational dynamics orchestrate positive and negative cooperativity during a kinase’s enzymatic cycle. Specifically, motions of the kinase backbone and side chains are not randomly distributed; rather they are tightly coupled to modulate both cooperativity and catalytic efficiency. Importantly, disruptions in these motions are distinct markers for dysfunctional kinases in disease states.