Poster abstracts

Poster number 87 submitted by Prabuddha Madubashitha

A study of aminoglycosides binding to 16S rRNA constructs

Prabuddha Madubashitha (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)

Abstract:
The development of resistance in pathogenic bacteria and adverse health effects are among the major challenges of using antibiotics. In developing better antibiotics, the knowledge of the binding of a particular compound to its target at the molecular level is very important. The objective of our study is to gain a better understanding of the binding affinity, binding site and drug-induced structural changes of the bacterial ribosome with potential antibiotics using a combination of biochemical and biophysical studies. Initially the binding of classical and modified aminoglycosides (AGs) to helix 44 (h44) of the aminoacyl-tRNA site (A site) of E. coli ribosomes was studied by using chemical probing. For the biophysical studies, the interactions between AGs and 27mer h44 constructs from E. coli, wild-type human mitochondrial, and a human mitochondrial mutant were studied by using nuclear magnetic resonance spectroscopy. Preliminary data suggest a difference between binding of AGs to wild-type human mitochondrial and human mitochondrial mutant h44 constructs, which can be used to explain the observed AG-related ototoxicity. In addition, a fluorescence-based assay is being employed to further study these interactions. These results will lead to a better understanding of drug-ribosome interactions, including drug side effects, at the molecular level.

Keywords: Ribosome, Aminoglycosides, Ototoxicity