Heme Protein Structure and Dynamics

描述（由申请人提供）：将进行结构和功能研究，以便在分子水平上了解血红素蛋白在基本生理过程中的作用，包括呼吸、代谢和细胞反应的调节。特别强调将放在新的一类血红素传感器蛋白。信号转导鸟苷酸环化酶和CooA，和血红素调节酶胱硫醚β合酶，已被选定为详细的表征和蛋白质构象变化的动力学研究。此外，金属离子插入血红素的决定因素将通过比较酶亚铁螯合酶与一组进行相同反应的催化抗体进行研究。共振拉曼光谱将被应用作为血红素基团的结构监测器，以及其与周围蛋白质和外源配体的相互作用。动力学研究将利用皮秒和更长时间尺度上的脉冲探测时间分辨共振拉曼光谱。从头计算与当前的DFT技术将被用来从光谱中提取最大的信息，并提供深入了解血红素-蛋白质相互作用的分子机制。

DESCRIPTION (provided by applicant): Structural and functional studies will be carried out in order to provide a molecular level 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 guanylate cyclase and CooA, and 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 metal ion insertion into heme will be studied by comparing the enzyme ferrochelatase with a set of catalytic antibodies that carry out the same reaction. 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 picosecond and longer time scales. Ab initio computation with current DFT techniques will be employed to extract maximum information from the spectra, and to provide insight into the molecular mechanisms of the heme-protein interactions.