Open Access. Powered by Scholars. Published by Universities.®
Biochemistry, Biophysics, and Structural Biology Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Secondary Functions And Novel Inhibitors Of Aminoacyl-Trna Synthetases, Patrick Wiencek
Secondary Functions And Novel Inhibitors Of Aminoacyl-Trna Synthetases, Patrick Wiencek
Graduate College Dissertations and Theses
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 …
Characterization Of A Non-Canonical Function For Threonyl-Trna Synthetase In Angiogenesis, Adam Christopher Mirando
Characterization Of A Non-Canonical Function For Threonyl-Trna Synthetase In Angiogenesis, Adam Christopher Mirando
Graduate College Dissertations and Theses
In addition to its canonical role in aminoacylation, threonyl-tRNA synthetase (TARS) possesses pro-angiogenic activity that is susceptible to the TARS-specific antibiotic borrelidin. However, the therapeutic benefit of borrelidin is offset by its strong toxicity to living cells. The removal of a single methylene group from the parent borrelidin generates BC194, a modified compound with significantly reduced toxicity but comparable anti-angiogenic potential. Biochemical analyses revealed that the difference in toxicities was due to borrelidin's stimulation of amino acid starvation at ten-fold lower concentrations than BC194. However, both compounds were found to inhibit in vitro and in vivo models of angiogenesis at …