Identifying the Role of His293 in Protein Arginine Methyltransferase 1 and Characterization of Agonists for Peroxisomal Proliferator Activating Receptors

Abstract

This thesis presents two proteins of interest: (1) protein arginine methyltransferase 1 (PRMT1) and (2) peroxisome proliferator activated receptors (PPARs). The purpose of this thesis is to assess the intermolecular interactions between substrate and important active site residues of PRMT1 and to characterize the major conformational changes induced by compound 9 upon PPAR and PPAR-γ coactivator 1 alpha (PGC-1α) to target diabetes. An overview of theoretical background of the computational methods applied in this research can be located in chapter 2. Chapter 3 dissects the PRMT1 active site, and gains insight into the significance of the H293 active site residue in product formation control. Chapter 4 decribes the efforts of a combined computational and experimental study of PPAR/PGC-1α/agonist complexes that were performed to explain the differences between agonists compounds 9, rosiglitazone, and other selective PPARγ modulators.