Talk abstracts

Talk on Saturday 12:20-12:40pm submitted by Yury Polikanov

From the structure and function of ribosome to disease-curing antibiotics

Yury Polikanov (University of Illinois at Chicago)

Antibiotic resistance in the US costs an estimated $20 billion a year, because many pathogenic microorganisms quickly develop resistance to the drugs. This demands a constant search for new antibiotics. Our current research is focused on one of the major targets of antibacterial drugs – the­ ribosome, which is a very complex molecular machine responsible for protein synthesis in all living organisms. Since ribosome inhibitors are among the most successful antimicrobial drugs in clinic, our ambition is to determine the structures of such inhibitors bound to their target in order to understand how they work and how they could be improved. Recently we established a biochemistry-inspired multifaceted approach, which allowed us not to only directly visualize interactions of various drugs with the ribosome with atomic precision, but also to assess the effects of the drug binding on the ribosome functionality. In my talk I will present our recent advances that enabled us to elucidate the mechanisms of action of novel classes of antibiotics, all of which are not represented among the clinically used drugs and, therefore, hold value for future structure-based rational drug design.

1. Metelev M, et al. (2017) Klebsazolicin inhibits 70S ribosome by obstruction of the peptide exit tunnel. Nature Chemical Biology. In press.

2. Almutairi MM, et al. (2017) Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins. Nucleic Acids Research. In press.

3. Osterman IA, et al. (2017) Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state. Nucleic Acids Research, DOI: 10.1093/nar/gkx413.

Keywords: Ribosome, Structure, Antibiotic