Understanding the effect of allosteric regulation of Aurora kinases on inhibitor binding

Abstract

Aurora kinase A and B regulate various signaling processes during mitosis, and their overexpression is associated with mitotic dysregulation and tumorigenesis. Many ATP-competitive inhibitors of Aurora kinases have been developed and are in various phases of clinical trials. However, the lack of correct stratification of the patient population along with a poor understanding of the structural dynamics of these kinases continue to pose a challenge in the development of Aurora inhibitors. Aurora A and B are tightly regulated by allosteric protein-protein interactions. I have tried to understand how the binding of allosteric partner-protein affects the protein dynamics, which in turn governs kinase-drug interactions.