This thesis describes research into the mode of function, inhibition, and evolution of the ribosomal catalytic center, the Peptidyl Transferase Center (PTC)--research that has already led to attempts at improving PTC antibiotics. The PhD candidate carried out two parallel studies. One using a combination of X-ray crystallography, biochemistry, molecular biology, and theoretical studies to obtain crystal structures of ribosomal particles with antibiotics that target the PTC, revealing the modes of action, resistance, cross-resistance and discrimination between ribosomes of eubacterial pathogens and eukaryotic hosts. In the second parallel study, the candidate synthesized a ribosomal substructure--one that may represent the minimal entity capable of catalyzing peptide bond formation--shedding light on the origin of the ribosome itself.

Nominated by the Weizmann Institute, Israel for a Springer Theses Prize This research has already led to attempts to improve PTC antibiotics Based on these findings further research into designing a functional construct mimicking a functional proto-ribosome has been initiated Includes supplementary material: sn.pub/extras

Inhalt

Introduction.- Methods.- Results.- Discussion.