Insights into Phosphoryl Transfer by the Thermophilic Protein Tyrosine Phosphatase, SsoPTP

Any organism, regardless of complexity, needs a reliable method for cell-to-cell communication. Phosphorylation is one of nature’s favorite ways of assisting cells in signal transduction. Conversely, dephosphorylation, the removal of phosphate, is the cell’s way of attenuating the signal provided by the initial phosphorylation. Without phosphatases, the hydrolysis of a phosphate monoester would take approximately 1 trillion years. However, with an enzyme catalyzing the reaction, it takes mere seconds. This dissertation focuses on a subfamily of phosphatases called protein tyrosine phosphatases (PTPs). PTPs specifically target phosphorylated tyrosines. A well-known example of PTPs is PTP1B, which specifically targets the human insulin receptor. Therefore, PTP1B is an excellent research target to study type 2 diabetes and obesity. Enzymes within the PTP family, like PTP1B, demonstrate clear protein motions that correlate with catalytic rate. We seek to explore the finer workings of phosphoryl transfer within this document by examining an archaeal thermophilic PTP, SsoPTP. Through the characterization of SsoPTP, we believe that our understanding of the role of protein motions within the family of PTPs will improve. Additionally, it is believed that archaeal enzymes like SsoPTP were the first PTPs in nature. The data found in these studies could provide further insights into how evolution has transformed phosphatases into some of the most powerful enzymes known