Ultraviolet Raman Spectroscopic Studies of Protein and Dynamics

蛋白质和动力学的紫外拉曼光谱研究

• 批准号: 7904708
• 负责人: THOMAS G. SPIRO
• 金额: $ 24.41万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-31 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904708
• 关键词: Alcohol dehydrogenase; Apoptosis; Behavior; Computer Simulation; Ferritin; Goals; Hemoglobin; Hybrids; Iron; Lasers; Lead; Lipids; Metals; Molecular; Molecular Conformation; Monitor; Motion; Mutagenesis; Nature; Protein Dynamics; Proteins; Pump; Raman Spectrum Analysis; Reaction; Site; Site-Directed Mutagenesis; Spectrum Analysis; Staging; Structure; Techniques; Time; cofactor; cytochrome c; enzyme activity; improved; infrared spectroscopy; protein folding; temperature jump; time use; ultraviolet; villin

DESCRIPTION (provided by applicant): The dynamical behavior of proteins will be investigated, using time-resolved Raman and infrared spectroscopies as probes of structure in real time. Laser temperature-jump techniques will be applied to the protein folding problem in order to characterize the earliest stages in folding and unfolding. T-jump studies will be extended to investigate protein motions tied to function: enzyme activity in alcohol dehydrogenase, iron release from ferritin, and apoptosis triggering by cytochrome c. The dynamics of protein allostery will be investigated, using hemoglobin as a paradigm. Pump-probe spectroscopic monitoring of the R-T conformation change will be used to define the reaction coordinate in molecular detail, using site-directed mutagenesis and metal substitution, in conjunction with computational modeling. By increasing our understanding of hemoglobin, these studies may lead to improved hematological therapies.

描述（由申请人提供）：将使用时间分辨的拉曼和红外光谱镜作为实时的结构探针研究蛋白质的动态行为。激光温度跳跃技术将应用于蛋白质折叠问题，以表征折叠和展开的最早阶段。 T-JUMP研究将进行扩展，以研究与功能相关的蛋白质运动：酒精脱氢酶中的酶活性，铁蛋白从铁蛋白释放以及细胞色素c触发的凋亡。将使用血红蛋白作为范式研究蛋白质变构的动力学。 R-T构象变化的泵探针光谱监测将用于使用位置定向的诱变和金属取代，并与计算建模相结合，以分子细节定义反应坐标。通过增加对血红蛋白的理解，这些研究可能会导致血液学疗法的改善。