STRUCTURE/FUNCTION OF RESPIRATORY HEMOPROTEINS

该项目的长期目标是了解 氧结合呼吸铁血球蛋白的结构与功能关系 如肌红蛋白和血红蛋白，通过化学修饰 血红素蛋白的特异性分子量及其特性 细胞的物理性质和生化生理功能 修饰过的血球蛋白。金属取代的肌红蛋白和血红蛋白， 尤其是钴卟啉取代的肌红蛋白和血红蛋白 以及它们相互作用的方式，这些双原子配体 作为氧气、一氧化碳和三氧化二氮，将通过 热力学和动力学测量以及光谱方法， 特别是EPR、核磁共振、共振拉曼和穆斯堡尔谱 技巧。这样的调查将使我们能够识别立体化学物质 以及影响分子动力学和热力学性质的电子因素 配基相互作用，配位的相关变化 假体基团及其三级和四级结构 分子，了解可逆配体的分子机制 结合、配体激活以及配体和效应器连接的亚基 这些呼吸性血色素蛋白中的协作性和变构，以及 最终设计出可能有效使用的人造血球蛋白 具有生物医学重要性的天然血球蛋白的替代品。因此， 拟议的项目主要集中在生理学和生物医学上。 组织中氧气输送和利用的重要方面。自.以来 血红蛋白协同作用和变构意志的分子机制 无疑提供了一个有用的线索来理解至关重要的监管角色 代谢中的变构酶和血红蛋白-一氧化氮 络合物经常被观察到是代谢的中间产物/副产物 在含氮致癌物质方面，拟议的项目将有广泛的 对生物医学的影响。

The long-term objective of this project is to understand the structure-function relationship in oxygen-linked respiratory hemoproteins such as myoglobin and hemoglobin by means of chemical modifications of specific molecular moieties of hemoproteins and characterization of physical properties and biochemical and physiological functions of such modified hemoproteins. Metal-substituted myoglobins and hemoglobins, particularly cobalt-porphyrin-substituted myoglobins and hemoglobins will be prepared and the mode of their interactions which diatomic ligands such as oxygen, carbon monoxide, and mitric oxide will be elucidated by thermodynamic and kinetic measurements and spectroscopic methods, especially EPR, NMR, resonance Raman, and Moessbauer spectroscopic techniques. Such investigations will allow us to identify stereochemical and electronic factors which affect kinetic and thermodynamic properties of ligand interaction, associated changes in the coordination of the prosthetic groups and the tertiary and quaternary structures of the molecules, to understand the molecular mechanism of reversible ligand binding, ligand activation, and ligand- and effector-linked subunit cooperativity and allostery in these respiratory hemoproteins, and eventually to design artificial hemoproteins which may be used as effective substitutes for natural hemoproteins of biomedical importance. Therefore, the proposed project sharply focuses on the physiological and biomedical vital aspects of oxygen delivery and utilization in tissues. Since the molecular mechanism of hemoglobin cooperativity and allostery will undoubtedly provide a useful clue to understand the vital regulatory role of allosteric enzymes in metabolism and since hemoprotein-nitric oxide complexes are frequently observed as intermediates/byproducts in metabolism of nitrogenous carcinogens, the proposed project will have wide-ranged biomedical implications.