X RAY CRYSTALLOGRAPHY OF ANTIBIOTICS BOUND TO RIBOSOMES

该项目的长期目标是通过在原子分辨率上解决核糖体亚基（或整个核糖体）的结构来推进对蛋白质翻译的理解。这个项目更直接的目标是通过晶体学来深入了解核糖体-抗生素的相互作用。具体来说，将各种抗体和抑制剂浸泡在核糖体晶体中或与核糖体共结晶，并在不同的傅立叶电子密度图中确定结合位点。将研究的一个关键抑制剂是肽基转移反应的直接类似物（CcdApPuro）。目前的研究主要集中在大核糖体亚基晶体上，其相位信息可在G A分辨率下获得。在这个分辨率下，结合抗生素很可能在不同的傅立叶电子密度图中被看到。这些抗生素的定位及其结合位点在6 A分辨率下的结构信息将为蛋白质翻译和抗生素对翻译的抑制提供新的见解。此外，随着相位信息的质量和分辨率的提高，抗生素实验获得的信息质量也有望提高。此外，当建立核糖体原子模型的任务开始时，了解这些抗生素结合位点的位置可能是有用的。

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.