Crystallography matters ... more!

Abstract

Striving to understand the fundamental process of the translation of the genetic code, a basic and most important process of life, we developed innovating methodologies and determined the structure and deciphered its mode of function of the ribosome, the universal cellular “factory” that performed the formation of the proteins (the cell workers) according to the genetic code. Owing to their vital role in cell life, the ribosomes are paralyzed by many antibiotics. Consequently, once we understood the basic issues in ribosome function, we focused on the inhibitory actions and synergism pathways of almost all ribosomal antibiotics. The results of these studies indicated the principles of differentiation between patients and disease carrying bacteria, suggested mechanisms leading to bacterial resistance and paved ways for improvement of existing antibiotics as well as for the design of advanced therapeutics capable of minimizing antibiotics resistance. 

However, as species specific diversity was detected in susceptibility to infectious diseases and in developing specific resistance mechanisms, we extended our structural studies to ribosomes from genuine pathogens. By determining the high resolution structures of the first ribosomal particle from a genuine multi-resistant pathogen with several antibiotics, we identified subtle, albeit highly significant structural elements in the antibiotics binding pockets that can account partially or fully for species specificity in resistance; revealed elements of species specificity and paved ways for improvement of existing antibiotics. Furthermore these studies and provided structural tolls for the design of “species specific antibiotics”, each of which targeting a specific bacterium, thus preserving the microbiome including the gut flora.

http://www.weizmann.ac.il/sb/faculty_pages/Yonath/

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2009/yonath-facts.html

http://xtal.dq.fct.unl.pt/iycr2014/Speakers.html