Date of Award
2018
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biochemistry
First Advisor
Christopher Francklyn
Second Advisor
Karen Lounsbury
Abstract
The aminoacyl-tRNA synthetases are a family of enzymes involved in the process of translation, more specifically, ligating amino acids to their cognate tRNA molecules. Recent evidence suggests that aminoacyl-tRNA synthetases are capable of aminoacylating proteins, some of which are involved in the autophagy pathway. Here, we test the conditions under which E. coli and human threonyl-tRNA synthetases, as well as hisidyl-tRNA synthetase aminoacylate themselves. These reactions are ATP dependent, stimulated by Mg2+, and are inhibited by increasing cognate tRNA concentrations. These data represent the foundation for future aminoacylation experiments, specifically delving into the relationship between the autophagy pathway and the aminoacylation of proteins.
Additionally, we provide evidence of the inhibitory abilities of the compound EHTS-0 on both E. coli and human threonyl-tRNA synthetases. Further, we also show that an EHTS-0 analog, EHTS-1, also significantly inhibits E. coli threonyl-tRNA synthetase but not the human enzyme. These data could be useful in determining the potential for EHTS-0 and EHTS-1 as possibly anti-angiogenic drugs.
Language
en
Number of Pages
67 p.
Recommended Citation
Wiencek, Patrick, "Secondary Functions And Novel Inhibitors Of Aminoacyl-Trna Synthetases" (2018). Graduate College Dissertations and Theses. 941.
https://scholarworks.uvm.edu/graddis/941