The aminoacyl-tRNA binding site (A-site), located in the small ribosomal subunit, ensures the fidelity of the mRNA translation process. The A-site is also a binding site for aminoglycoside antibiotics. Aminoglycosides have higher affinities towards the bacterial than human A-site. However, they also bind to human ribosomes, which results in severe side effects of these antibacterials. To explain the differences in affinities and facilitate the design of less toxic antibiotics we compared the conformational properties of the human and bacterial A-site variants using molecular dynamics and enhanced sampling methods. The simulations show that human mitochondrial A-site variants are more rigid than the bacterial and human cytoplasmic ones. Also, the difference in the mobility between the native human mitochondrial A-site and its naturally occurring mutant (A1555G) may explain why aminoglycosides bind more strongly to the latter.

Comparing the dynamics of the bacterial and human ribosomal A-site

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.