Factors Influencing the Local Dynamics of Redox Metalloproteins

这个无机、生物无机和有机金属化学项目的研究奖支持蒙大拿大学的Bruce Bowler教授的工作，他使用细胞色素c作为模型系统，对金属蛋白的构象动力学及其功能之间的关系进行了基础研究。细胞色素c参与与活细胞能量产生有关的电子转移化学。它也介导程序性细胞死亡。这种蛋白质的血红素位于靠近蛋白质表面的缝隙中，这个缝隙的打开和关闭被认为在其功能中起作用。通过与无机化合物的电子转移反应以及小分子与血红素铁原子的结合，可以观察到血红素缝隙打开的动力学。血红素缝隙附近氨基酸的突变被用来测试局部结构刚度对血红素缝隙动力学的影响。影响血红素口袋外部分蛋白质稳定性的突变也被用于测试更远的蛋白质结构部分对重要功能血红素缝隙动力学的影响。这项研究资助为研究生和博士后提供培训，从而通过增加训练有素的科学家数量来加强我们的研究基础设施。蒙大拿大学招收了8%的少数族裔学生，其中一半是印第安人，化学与生物化学系主持了一个由美国国家科学基金会赞助的本科生研究经历项目，该项目大量招收蒙大拿部落学院的学生。因此，代表性不足的少数民族有望参与这项研究。了解控制蛋白质动力学和功能的因素将为合理操纵蛋白质功能提供基础知识，从而设计出具有优化和新颖活性的蛋白质，这些蛋白质对工业上重要的化学转化具有潜在的重要性。特别是对于细胞色素c，这些知识可以用于设计分子电子器件的组件。

This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Bruce Bowler at the University of Montana to carry out fundamental studies on the relationship between the conformational dynamics of metalloproteins and their functions, using cytochrome c as a model system. Cytochrome c is involved in electron transfer chemistry related to energy production in living cells. It also mediates programmed cell death. The heme of this protein sits in a crevice near the surface of the protein and the opening and closing of this crevice is believed to play a role in its function. The dynamics of heme crevice opening are observed using electron transfer reactions with inorganic compounds and also through the binding of small molecules to the iron atom of the heme. Mutations of amino acids adjacent to the heme crevice are being used to test the effect of local structural stiffness on the dynamics of the heme crevice. Mutations, which affect the stability of portions of the protein outside of the heme pocket, are also being used to test the effect of more distant parts of the protein structure on the dynamics of the functionally important heme crevice. This research grant provides training for graduate students and postdoctoral fellows thus enhancing our research infrastructure by growing the pool of trained scientists. The University of Montana enrolls 8% minority students, half of whom are Native Americans, and the Department of Chemistry & Biochemistry hosts an NSF-sponsored Research Experiences for Undergraduates program that recruits heavily from tribal colleges in Montana. Thus, underrepresented minorities are expected to participate in this research. Understanding the factors that control protein dynamics and thus function will provide a base of knowledge that will permit rational manipulation of protein function, allowing design of proteins with both optimized and novel activities with potential importance for industrially-important chemical transformations. For cytochrome c, specifically, this knowledge could be used to design components for molecular electronics devices.