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Heme Protein Structure and Dynamics

血红素蛋白质结构和动力学

基本信息

批准号：
8123669
负责人：
THOMAS G. SPIRO
金额：
$ 9.99万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2011-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Structural and functional studies will be carried out in order to provide a molecular level of understanding of the role of heme proteins in fundamental physiological processes, including respiration, metabolism, and the regulation of cellular responses. Special emphasis will be placed on the new class of heme sensor proteins. The signal transducers CooA and the H-NOX family of proteins, as well as the heme-regulated enzyme cystathionine beta synthase, have been selected for detailed characterization and dynamical studies of protein conformational change. In addition, the determinants of ligand discrimination by the heme sensors will be studied, with special emphasis on NO selectivity. Resonance Raman spectroscopy will be applied as a structural monitor of the heme group, and of its interaction with the surrounding protein and with exogenous ligands. Dynamical studies will utilize pulse-probe time-resolved resonance Raman spectroscopy on nanosecond and longer time scales. Computation with current DFT and QM/MM techniques will be employed to extract maximum information from the spectra, and to provide insight into the molecular mechanisms of the heme-protein interactions. Heme proteins are critical to human health, and their malfunction is associated with many disease states. Heme proteins ferry oxygen from the lungs to the tissues and then convert oxygen's energy to physiologically useful forms. Other heme proteins are regulators of critical biological processes. Understanding how heme proteins work at the molecular level is an important goal and may lead to new therapies.

描述（由申请人提供）：将进行结构和功能研究，以提供对血红素蛋白在基本生理过程中的作用的分子水平的理解，包括呼吸，代谢和细胞反应的调节。特别的重点将放在血红素传感蛋白的新类别。信号转导CooA和H-NOX家族的蛋白质，以及血红素调节酶-半胱硫氨酸-合成酶，已经被选择用于蛋白质构象变化的详细表征和动力学研究。此外，血红素传感器对配体识别的决定因素将被研究，特别强调NO的选择性。共振拉曼光谱将被应用于血红素群的结构监测，以及它与周围蛋白质和外源配体的相互作用。动力学研究将在纳秒或更长的时间尺度上利用脉冲探针时间分辨共振拉曼光谱。利用当前的DFT和QM/MM技术计算将从光谱中提取最大的信息，并提供血红素-蛋白质相互作用的分子机制的见解。血红素蛋白对人体健康至关重要，其功能障碍与许多疾病状态有关。血红素蛋白将氧气从肺部运送到组织，然后将氧气的能量转化为生理上有用的形式。其他血红素蛋白是关键生物过程的调节因子。了解血红素蛋白如何在分子水平上起作用是一个重要的目标，并可能导致新的治疗方法。