CRYSTALLOGRAPHIC STRUCTURE ANALYSES OF PROTEIN/LIGAND COMPLEXES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该提案包括两个涉及蛋白质-配体相互作用研究的项目。 第一个是继续寻找视紫红质及其与其他信号蛋白复合物的有序晶体。 G蛋白偶联受体如何响应其环境并与G蛋白相互作用以产生细胞内信号在分子结构水平上尚不清楚。 我们正试图结晶与信号过程相关的复合物，并希望使用同步辐射来确定它们的结构。 我们目前的晶体很小，而且排列不整齐。 如果没有同步辐射源，很难确定它们的反射效果如何。 我们的第二个项目涉及获得高或超高分辨率的衍射数据链霉亲和素突变体和它们的生物素复合物。 我们希望比较分子动力学模拟和各向异性原子位移参数，以更好地了解蛋白质/小分子（药物？）交互. 我们目前有几个高分辨率的数据集进行比较，但我们预计将扩大我们的研究，包括更多的突变体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This proposal covers two projects involving studies of protein-ligand interactions. The first is a continuing search for well-ordered crystals of rhodopsin and its complexes with other signaling proteins. How G protein-coupled receptors respond to their environment and interact with G proteins to create intracellular signals is not understood at the molecular structure level. We are attempting to crystallize complexes relevant to the signaling process and want to use synchrotron radiation to determine their structures. Our current crystals are small and poorly-ordered. How well they diffract would be difficult to determine without access to synchrotron sources. Our second project involves obtaining high or ultra-high resolution diffraction data for streptavidin mutants and their biotin complexes. We want to compare molecular dynamics simulations and anisotropic atomic displacement parameters to better understand the dynamics of protein/small molecule (drug?) interactions. We currently have several high-resolution data sets for the comparison, but we anticipate expanding our studies to include additional mutants.