CRYSTALLOGRAPHIC STRUCTURE ANALYSES OF PROTEIN/LIGAND COMPLEXES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 三个研究蛋白质/配体相互作用的结晶学项目需要束流时间。视紫红质是一种G蛋白偶联受体，参与视觉的第一个分子步骤。计划进行几个专门的实验，以观察导致该蛋白质信号转导的构象变化。这些实验将对其他GPCR的药物设计工作产生相当大的影响，这些GPCR约占目前所有药物靶标的三分之一。束时间还将用于链霉亲和素突变体的继续研究，以帮助了解蛋白质和生物素的紧密结合。需要同步辐射来研究小晶体，并获得一些链霉亲和素/生物素络合物的超高分辨率数据集。最后，对于谷胱甘肽S转移酶复合体和产生小晶体或高分辨率衍射图的突变体，需要束流时间。这些研究旨在了解这种药物解毒酶的作用机制和配基结合特性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Beam time is requested for three crystallographic projects studying protein/ligand interactions. Rhodopsin is the G-protein coupled receptor (GPCR) involved in the first molecular steps in vision. Several specialized experiments for observing the conformational change leading to signal transduction for this protein are planned. These experiments will have considerable impact on drug design efforts for other GPCRs making up about a third of all current drug targets. Beam time will also be used for continued studies of streptavidin mutants to aid in understanding the tight binding of the protein and biotin. Synchrotron radiation is needed to study small crystals and obtain ultra-high resolution data sets for some of the streptavidin/biotin complexes. Finally, beam time is requested for glutathione S-transferase complexes and mutants yielding small crystals or high resolution diffraction patterns. These studies are aimed at understanding the mechanism and ligand binding properties of this drug detoxication enzyme.