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。特别的重点将放在血红素传感蛋白的新类别。信号转导鸟苷酸环化酶和CooA，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，将通过比较铁螯合酶与一组进行相同反应的催化抗体来研究金属离子插入血红素的决定因素。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。动力学研究将在皮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。采用当前DFT技术的从头计算将从光谱中提取最大信息，并提供对血红素-蛋白质相互作用的分子机制的见解。

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.