Zoom link:  https://purdue-edu.zoom.us/meeting/register/tJUtd-2rrTIqEt28s1D20iZPi-9RRDGj76V5 

The seminar is entitled: "Small molecule targeting of a unique leucine carboxyl-methylation modification to provmote complex stability of a potent tumor suppressor."

Post-translational modifications (PTMs) are molecular switches that define cellular protein activity in all living organisms. Impairment of protein phosphatases, including the family of serine/threonine phosphatases designated PP2A, is essential for the pathogenesis of many diseases, including cancer. The ability of PP2A to dephosphorylate hundreds of proteins is regulated by over 40 retulatory "B" subunits that compete for assembly with a scaffolding A and a catalytic C subunit. Work from our group reveals how a small molecule, DT-061, specifically stabilizes the B56a-PP2A holoenzyme in a fully assembled, active state to dephosphorylate the well-known oncoprotein, c-MyC. The dryg-bound complex defines the molecular interactions between DT-061 and all three PP2A subunits that prevent dissociation of the active enzyme. Thus, our findings provide insights into PP2A complex assembly and identify a unique interfacial stabilizing mode of action for therapeutic targeting and the development of phosphatase-based therapeutics tailored against disease specific phospho-protein targets.

This seminar is sponsored by the Molecular Biophysics Training Program (MBTP) and Structural and Computational Biology and Biophysics (SCCB).