MOTOR PROTEIN-INHIBITOR COMPLEX STRUCTURE DETERMINATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。通过小分子控制细胞骨架蛋白的作用是开发新疗法的主要途径。我们感兴趣的是在原子分辨率水平上了解小分子调节剂对各种细胞骨架蛋白的调节机制。更具体地说，我们的研究涉及到调节运动蛋白等分子马达蛋白的小分子之间的相互作用。Kinesin是一类运动蛋白家族，对多种基于微管的细胞运输活动至关重要，包括神经元运输、有丝分裂纺锤体的组装和维持以及细胞内运输。细胞动力学已经发表了关于KSP/Eg51等有丝分裂运动蛋白的结构以及KinI2和Kip3d3微管解聚的结构特征的结果。目前，我们正在努力获得小分子复合体中的马达蛋白结构。因此，这项工作将为开发基于结构的药物设计提供基础，这将有助于我们的药物发现工作。

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. Control of the action of cytoskeletal proteins by small molecules presents a major avenue for developing novel therapies. Our interest is directed towards understanding mechanism of regulation of various cytoskeletal proteins by small molecule modulators at the level of atomic resolution. More specifically, our studies involve looking at the interactions between small molecules that modulate molecular motor proteins such as kinesins. Kinesins are a family of motor proteins essential for a variety of microtubule based cellular transport events including neuronal transport, mitotic spindle assembly and maintenance, and intracellular trafficking. Cytokinetics has published results on the structure of the mitotic kinesins like KSP/Eg51 and structural characterization on microtubule depolymerization of kinesins KinI2 and Kip3d3. Currently, we are working on obtaining structures of motor proteins in complex with small molecules. Therefore, this work will provide the foundation for developing structure-based drug design that will aid in our drug discovery efforts.