MOTOR PROTEIN-INHIBITOR COMPLEX STRUCTURE DETERMINATION

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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.