Investigation of the Molecular Determinants and Extrinsic Factors That Regulate PRMT Product Specificity
Date of Award:
Doctor of Philosophy (PhD)
Chemistry and Biochemistry
Joan M. Hevel
Joan M. Hevel
Protein arginine methylation is an important modification of proteins, involved in many cellular processes. Some examples are transcription, RNA editing, cellular communication, DNA repair, viral replication and chromatin remodeling. In recent years, the significance of protein arginine methyltransferases (PRMTs) in human diseases has been increasingly studied, especially in cardiovascular disease and cancer. Although the importance of these enzymes is recognized, the understanding of how exactly PRMTs function is still limited. Very little information is available to explain how or why any of the different PRMTs interact with other proteins or, what determines where in that protein to place their methyl marks. Adding to this complexity, placing one of the three different methylation marks (products) or the other (mono methyl arginine MMA, asymmetric dimethyl ADMA, or symmetric dimethyl SDMA) on a protein can cause a cell to respond differently. Therefore, if we really want to understand how this family of proteins functions and how to control them, it’s essential that we understand how they achieve their product specificity; this means, how they decide which methyl mark to place on an interacting protein. In order to better understand the product specificity of this family of enzymes, I have been using as a model two Protein arginine methyltransferases that are responsible different methylation marks: PRMT1, which can make both ADMA and MMA and TbPRMT7, which can only make MMA. Using the information that crystal structure of these enzymes provide and what we already know about how PRMT activity is regulated, my aim is to better understand the mechanisms by which these enzymes achieve their product specificity.
Cáceres, Tamar B., "Investigation of the Molecular Determinants and Extrinsic Factors That Regulate PRMT Product Specificity" (2019). All Graduate Theses and Dissertations. 7549.
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