Ada Yonath

As a structural biologist, I have been focusing on protein biosynthesis mechanisms, using ribosomal crystallography, a research line pioneered by my research team in the beginning of the eighties. We identified eubacterial ribosomes crystallizable under conditions allowing optimal functional activity, which yielded complete high-resolution structures of functionally relevant conformations of both ribosomal subunits. Consequently we discovered a sizable symmetry related region within the otherwise asymmetric ribosome, and revealed the parameters crucial for precise substrates placement. A thorough analysis confirmed that the ribosome contributes positional catalysis to its dual tasks: peptide bond formation and aminoacid polymerization. We discovered the unified ribosomal machinery for peptide-bond formation, translocation and nascent protein progression into their exit tunnel. This tunnel, visualized by us in the mid-eighties, is one of the main targets for antibiotics. As we are focusing on species proved to be suitable pathogen models, we elucidated modes of action of over twenty different antibiotics, belonging to a dozen different antibiotic-families, all complexed with ribosomes at clinically relevant concentrations. Further analysis provided the structural bases for antibiotics synergism, clarified antibiotics selectivity and illuminated resistance mechanisms, thus paving the way for structural based drug design. We also identified structural elements allowing the tunnel's dynamic, thus enabling ribosomal involvement in discrimination and intra-cellular regulation.