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

来源：
https://reporter.nih.gov/project-details/8123669
关键词：
Binding Biological Process Cystathionine Cystathionine beta-Synthase Discrimination Disease Enzymes Goals Health Heme Heme Group Hemeproteins Human Lead Ligands Lung Metabolism Molecular Monitor Oxygen Physiologic pulse Physiological Processes Protein Family Proteins Raman Spectrum Analysis Respiration Role Signal Transduction Spectrum Analysis Techniques Testing Time Tissues Transducers Work adduct cell growth regulation computer studies electronic structure insight nanosecond protein structure response sensor

Binding Biological Process Cystathionine Cystathionine beta-Synthase Discrimination Disease Enzymes Goals Health Heme Heme Group Hemeproteins Human Lead Ligands Lung Metabolism Molecular Monitor Oxygen Physiologic pulse Physiological Processes Protein Family Proteins Raman Spectrum Analysis Respiration Role Signal Transduction Spectrum Analysis Techniques Testing Time Tissues Transducers Work adduct cell growth regulation computer studies electronic structure insight nanosecond protein structure response sensor

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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，以提供分子对血红素蛋白在基本生理过程中的作用的了解，包括呼吸，代谢和细胞反应的调节。特别重点将放在新的血红素传感器蛋白上。已经选择了信号传感器COOA和蛋白质的H-NOX家族，以及血红素调节的胱胱氨酰胺β合酶，以详细表征和动力研究蛋白质构象变化。此外，将研究血红素传感器歧视的决定因素，并特别强调无选择性。共振拉曼光谱法将作为血红素组的结构监测仪，以及与周围蛋白质和外源配体的相互作用。动力学研究将利用脉冲 - 探针时间分辨的共振拉曼光谱在纳秒和更长的时间尺度上。使用当前DFT和QM/MM技术的计算将采用从光谱中提取最大信息，并深入了解血红素蛋白相互作用的分子机制。血红素蛋白对人类健康至关重要，其故障与许多疾病状态有关。血红素蛋白从肺部将氧气转向组织，然后将氧气的能量转化为生理有用的形式。其他血红素蛋白是关键生物学过程的调节剂。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，并可能导致新的疗法。