X RAY CRYSTALLOGRAPHY OF ANTIBIOTICS BOUND TO RIBOSOMES

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DESCRIPTION The long term goal of this project is to advance the understanding of protein translation by solving the structures of ribosomal subunits (or of entire ribosomes) at atomic resolution. The more immediate goal of this project is to gain insight into ribosome-antibiotic interactions through crystallography. Specifically, various antibodies and inhibitors will be soaked into ribosomal crystals or co-crystalized with ribosomes, and the binding sites identified in difference Fourier electron density maps. One key inhibitor that will be studied is an analogue of the immediate of the peptidyl transfer reaction (CcdApPuro). Current research focuses on crystals of the large ribosomal subunit of Haloarcula marismortui for which phase information is available at G A resolution. At this resolution bound antibiotics are likely to be seen in difference Fourier electron density maps. Location of these antibiotics and structural information about their binding sites at 6 A resolution would provide new insight into protein translation and into antibiotic inhibition of translation. In addition, as the quality and resolution of the phase information is expected to improve, correspondingly, the quality of information gained from the antibiotic experiments is expected to improve. In addition, knowledge of the location of these antibiotic binding sites is likely to be useful when the task of building an atomic model of ribosomes begins.