Biochemistry Seminar: Gianluigi Veglia
Wed, Oct 16
12:00 PM — 1:00 PM
Marshak Science Bldg160 Convent Avenue
Marshak Science Bldg, MR-1027
Gianluigi Veglia: "Protein Kinase A & Conformational Dynamics"Gianluigi Veglia, Professor, Dept of Chemistry and
Dept of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, will give a talk titled "Protein Kinase A & Conformational Dynamics: Not too fast...not too slow...but just right."
ABSTRACT: Protein kinases mediate a myriad of cell signaling events. Protein kinase A (PKA) is considered the prototypical kinase, sharing its catalytic core (PKA-C) with many kinases. We have analyzed PKA-C’s conformational dynamics in the slow and fast scale of NMR spectroscopy and found that the slow time scale dynamics are linked with the enzyme turnover. Motions synchronous with the kcat are initiated upon nucleotide binding and pervade the entire enzyme, defining a dynamically committed state. The binding of inhibitors quench the enzyme’s conformational dynamics, creating a dynamically quenched state. We also found a mutant of PKA-C that enhances the motions in the fast time scale. However, these enhanced motions reduce the catalytic efficiency of the kinase. We conclude that the conformational dynamics of the enzyme is linked to the overall turnover, and an increase or decrease of these motions has negative effects on the catalytic cycle.