Pharmacology & Chemical Biology Seminar Series
10/22/2020 - 12:00 PM-1:00 PM
"Using Structure to define the Function and Selectivity of Phosphatases"

Wolfgang Peti, Ph.D. 
Homer C. and Emily Davis Weed Endowed Professor
College of Medicine, University of Arizona

We will present data how the most well-studied PSPs—Protein Phosphatase 1 (PP1), Protein Phosphatase 2A (PP2A) and Protein Phosphatase 2B (PP2B, PP3 or Calcineurin)—which are responsible for more than 2/3 of all eukaryotic dephosphorylation reactions, become highly specific enzymes. Using multiple orthogonal approaches, we show that this specificity is achieved by both the recruitment of distinct regulatory proteins to PSPs to generate highly specific holoenzymes and through the direct binding of PSPs to their substrates using newly discovered substrate binding motifs. Taken together, these data not only show how PSPs achieve specificity but also provides immediate opportunities for both identifying the plethora of PSP substrates in the cell and for the design of novel drugs that target distinct PSP holoenzymes.


Melanie McClain
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