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）：将使用时间分辨拉曼和红外光谱作为实时结构探针来研究蛋白质的动态行为。激光跳温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 跳跃研究将扩展到研究与功能相关的蛋白质运动：乙醇脱氢酶的酶活性、铁蛋白的铁释放以及细胞色素 c 触发的细胞凋亡。将使用血红蛋白作为范例来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定义分子细节的反应坐标，使用定点诱变和金属取代，并结合计算模型。通过增加我们对血红蛋白的了解，这些研究可能会改善血液疗法。