Date of Award:

5-2013

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Joan M. Hevel

Committee

Joan M. Hevel

Committee

Lance C. Seefeldt

Committee

Sean J. Johnson

Abstract

Enzymes are the machines of our cells. Just like machines, it takes a lot of energy to create them, and they then serve only the function they were created for. If we want to change the function of a machine, we need to modify it. Similarly, enzymes can be modified after their creation to give them additional function. These modifications can do a variety of things including activating (on) or inactivating (off) an enzyme, changing the enzyme’s location in the cell, and targeting the enzyme for destruction. This thesis focuses on a single class of enzymes, protein arginine methyltransferases (PRMTs), which are capable making small modifications to other proteins. This modification is called methylation because the enzyme transfers one or two methyl groups to specific a specific location(s) on the target protein (substrate).

This small but significant change is involved in cellular processes such as transcriptional regulation, DNA repair, subcellular localization, and signal transduction. Due to PRMTs broad involvement in the cell, it is unsurprising that protein methylation is involved in several types of cancer, cardiovascular disease, and many others. Detailed study of PRMTs to understand methyl group transfer, substrate targeting, and how they are controlled by the cell is essential for the development of therapeutic drugs capable of treating diseases associated with protein arginine methylation. This thesis presents studies which continue to provide insight into the function of PRMTs by addressing the effects of oxidative stress on PRMT1, how PRMTs interact with their substrates at the atomic level, and how PRMTs are involved in the processing of RNAs.

Checksum

6cc73592e0aee6057a90b8bcb046ff8f

Included in

Biochemistry Commons

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