Poster abstracts
Poster number 89 submitted by Prabuddha Madubashitha
A study of aminoglycosides binding to 16S rRNA
Prabuddha Madubashitha (Department of Chemistry, Wayne State University, Detroit, MI 48202), Evan Jones (Department of Chemistry, Wayne State University, Detroit, MI 48202), Laimar Garmo (Department of Chemistry, Wayne State University, Detroit, MI 48202), Christine S. Chow (Department of Chemistry, Wayne State University, Detroit, MI 48202)
Abstract:
Adverse health effects including ototoxicity is one of the major challenges of using aminoglycosides (AG) as antibiotics. In developing AG-based antibiotics with low ototoxic potential, knowledge of the binding of a particular AG to its target at the molecular level is important. The objective of our study is to gain a better understanding of the binding affinity and drug-induced structural changes of classical and modified AGs with helix 44 (h44) at the aminoacyl-tRNA site (A site) of 16S rRNA. The interactions between AGs and h44 constructs from E. coli, wild-type human mitochondria, and human mitochondrial mutant were studied by using a fluorescence-based assay and nuclear magnetic resonance spectroscopy. The data reveal a difference between binding of AG analogues to wild-type human mitochondrial h44 compared to E. coli and human mitochondrial mutant h44 constructs, which can be used to explain the observed AG-related ototoxicity. These results will lead to a better understanding of drug-rRNA interactions at the molecular level.
Keywords: aminoglycosides, ototoxicity, mitochondria