Life Sciences Commons^™

Characterization Of The Product Specificity And Kinetic Mechanism Of Protein Arginine Methyltransferase 1, Shanying Gui

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Protein enzymes perform a vast array of functions within living organisms, catalyzing various metabolic reactions including DNA replication, DNA repair, protein synthesis, etc. In order to maintain proper cellular functions, enzymes need to be accurately regulated under different circumstances. Specifically, enzymes can be modified after their creation to give them additional functions. These modifications can do a variety of things including activating (turning on) or inactivating (turning off) an enzyme, changing what proteins or molecules can interact with the enzyme, changing the enzyme’s location in the cell, and/or targeting the enzyme for destruction. This dissertation focuses on a single class …

Characterization Of The Substrate Specificity And Mechanism Of Protein Arginine Methyltransferase 1, Whitney Lyn Wooderchak

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Protein arginine methyltransferases (PRMTs) posttranslationally modify protein arginine residues. Type I PRMTs catalyze the formation of monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA) via methyl group transfer from S-adenosyl methionine onto protein arginine residues. Type II PRMTs generate MMA and symmetric dimethylarginine. PRMT-methylation affects many biological processes. Although PRMTs are vital to normal development and function, PRMT-methylation is also linked to cardiovascular disease, stroke, multiple sclerosis, and cancer.

Thus far, nine human PRMT isoforms have been identified with orthologues present in yeast, plants, and fish. PRMT1 predominates, performing an estimated 85% of all protein arginine methylation in vivo. Yet, the substrate …