Targeting Functional Centers of the Ribosome
Targeting Functional Centers of the Ribosome By Chen Davidovich (auth.)
2011 | 74 Pages | ISBN: 3642169309 | PDF | 3 MB
2011 | 74 Pages | ISBN: 3642169309 | PDF | 3 MB
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.