Dynamical and Functional Characterization of IGPS

IGPS 的动态和功能特性

• 批准号: 7056458
• 负责人: HIROKO SHIMADA
• 金额: $ 5.04万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056458
• 关键词: allosteric site; ammonia; conformation; electron spin resonance spectroscopy; enzyme complex; enzyme mechanism; enzyme substrate; enzyme substrate analog; glycerol; imidazole; isomerase; membrane channels; molecular dynamics; nuclear magnetic resonance spectroscopy; phosphates; postdoctoral investigator; protein structure function

DESCRIPTION (provided by applicant): Flexibility of proteins has been well observed and a role of such dynamics in protein functions seems inevitable. My research interest is the relationship between the dynamic and structural properties of proteins and the function of proteins. The study will be performed on the bacterial heterodimeric enzyme complex imidazole glycerol phosphate (IGP) synthase, a key metabolic enzyme which links amino acid and nucleotide biosynthesis. Biochemical and x-ray crystallographic studies indicate a tight coupling between the two reactions in distinct active sites, suggesting a dynamical role in function. Nonetheless, the details on the exact mechanism regarding the allosteric interactions are still unknown, and that is my very motivation to investigate the dynamics of this enzyme complex. NMR enables non-perturbing measurement of the residue- by-residue dynamics. Comparison of IGP synthase motion alone and substrate(s) or substrate analogue(s)-enzyme complexes will enable characterization of structural and dynamical contributions to function. The study will be carried out by combining NMR structural and spin-relaxation measurements with biochemical characterization of IGP synthase activity.

描述（由申请人提供）：已经充分观察到蛋白质的柔性，并且这种动力学在蛋白质功能中的作用似乎是不可避免的。我的研究兴趣是蛋白质的动力学和结构特性与蛋白质功能之间的关系。本研究将对细菌异二聚体酶复合物咪唑甘油磷酸（IGP）合酶进行研究，该合酶是连接氨基酸和核苷酸生物合成的关键代谢酶。生物化学和X射线晶体学研究表明，在不同的活性位点的两个反应之间的紧密耦合，这表明功能的动态作用。尽管如此，关于变构相互作用的确切机制的细节仍然是未知的，这是我研究这种酶复合物的动力学的动力学。NMR使得能够无干扰地测量逐残基动力学。比较单独的IGP合酶运动和底物或底物类似物-酶复合物将能够表征对功能的结构和动力学贡献。该研究将通过结合NMR结构和自旋弛豫测量与IGP合酶活性的生化表征来进行。