MOTOR PROTEIN-INHIBITOR COMPLEX STRUCTURE DETERMINATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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。我们的兴趣是在原子分辨率水平上理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，我们的研究涉及调节分子马达蛋白（如驱动蛋白）的小分子之间的相互作用。驱动蛋白是一类对多种基于微管的细胞转运事件（包括神经元转运、有丝分裂纺锤体组装和维持以及细胞内运输）必不可少的马达蛋白家族。Cytokerase已经发表了关于有丝分裂驱动蛋白如KSP/Eg 51的结构的结果，以及关于驱动蛋白KinI 2和Kip 3d 3的微管解聚的结构表征。目前，我们正致力于获得与小分子复合的马达蛋白的结构。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.