Date of Award
Spring 4-17-2013
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Yujun George Zheng
Abstract
Protein arginine methyltransferase, PRMT, is a family of epigenetic enzymes that methylate arginine residues on histone and nonhistone substrates which result in a monomethylation, symmetric dimethylation or asymmetric dimethylation via the transfer of a methyl group from S-adenosyl-L-methionine (SAM). We discovered a novel interaction between two PRMT isoforms: PRMT1 interacts and methylates PRMT6. In this study site-directed mutagenesis was performed on selected arginines identified from tandem mass spectrometric analysis to investigate major methylation sites of PRMT6 by PRMT1. In combination with radiometric methyltransferase assays, we determined two major methylation sites. Methylations at these sites have significant effects on the nascent enzymatic activity of PRMT6 in H4 methylation. PRMTs have the ability to homodimerize which have been linked to methyltransferase activity. We designed dimerization inhibitors (DMIs) to further investigate the need for dimerization for enzyme activity. Preliminary results suggest that the monomeric form of PRMT1 retains methyltransferase activity comparable to that of the uninhibited PRMT1.
DOI
https://doi.org/10.57709/4078981
Recommended Citation
Canup, Brandon S., "Discovery of Novel Cross-Talk between Protein Arginine Methyltransferase Isoforms and Design of Dimerization Inhibitors." Thesis, Georgia State University, 2013.
doi: https://doi.org/10.57709/4078981