RUI: The Role of Protein Dynamics in Catalysis and Subunit Cooperativity

RUI：蛋白质动力学在催化和亚基协同性中的作用

• 批准号: 0448905
• 负责人: Ellis Bell
• 金额: --
• 依托单位: University of Richmond
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0448905&HistoricalAwards=false
• 关键词: RUI; Role; Protein; Dynamics; Catalysis

This research will advance our understanding of how the dynamic properties of proteins play a critical role in the enzymes involved with the integration of protein, carbohydrate, and fat metabolism. The project will investigate the linkage between dynamic protein structure and both catalysis and the regulation of activity in three enzymes that play central roles in metabolism: glutamate dehydrogenase, malate dehydrogenase, and 3 phosphoglycerate dehydrogenase. Communication between subunits affecting catalysis and substrate binding regulate each of these enzymes. The roles of individual side chains in catalysis or in communication between subunits will be probed using site-specific mutations. The effects of mutations will be studied by functional assays, structural analysis using X ray crystallography and mass spectrometry, and computational approaches. The hypothesis that both catalytic activity and biological regulation involve changes in the dynamic properties of the protein will be directly tested by engineering flexibility changes in various regions of the protein and correlating the effects with alterations in both activity and subunit communication. Broader Impacts: The research is integrated fully into the education of undergraduates. Students will work on individual research projects, take laboratory courses with the research embedded into the course, or may take a research-based course for non-science majors. Students are integrally involved in the design of experiments, conduct of the research, and data analysis and presentation. Students become involved in their first year and often follow the research for 2-3 years. The research brings both a quantitative and physical understanding of biological processes to the participating students. They also participate in outreach to area elementary schools to bring the excitement of science to local children and their teachers. Students engaged in the project are drawn from the University of Richmond and Virginia State University.

这项研究将推进我们对蛋白质的动态特性如何在参与蛋白质，碳水化合物和脂肪代谢整合的酶中发挥关键作用的理解。 该项目将研究动态蛋白质结构与代谢中起核心作用的三种酶的催化和活性调节之间的联系：谷氨酸脱氢酶，苹果酸脱氢酶和3磷酸甘油酸脱氢酶。影响催化和底物结合的亚基之间的通讯调节这些酶中的每一种。将使用位点特异性突变来探测各个侧链在催化或亚基之间的通信中的作用。 突变的影响将通过功能测定、使用X射线晶体学和质谱的结构分析以及计算方法来研究。催化活性和生物调节都涉及蛋白质的动态性质的变化的假设将直接测试的工程灵活性的变化，在蛋白质的各个区域和相关的影响与活性和亚基通信的改变。更广泛的影响：研究完全融入本科生的教育。学生将从事个人研究项目，参加实验室课程，将研究嵌入课程中，或者可以参加非科学专业的研究课程。学生整体参与实验的设计，研究的进行，数据分析和演示。学生在第一年就参与其中，通常会跟踪研究2-3年。这项研究为参与的学生带来了对生物过程的定量和物理理解。 他们还参与到地区小学的外展活动中，为当地的孩子和他们的老师带来科学的兴奋。 参与该项目的学生来自里士满大学和弗吉尼亚州立大学。