STRUCTURE AND FUNCTION OF RESPIRATORY HEMOPROTEINS

本项目的长期目标是了解 氧联呼吸血红素蛋白结构与功能关系 例如肌红蛋白和血红蛋白， 血红素蛋白的特定分子部分和血红素蛋白的表征 物理性质和生物化学和生理功能， 修饰血红素蛋白 金属取代的肌红蛋白和血红蛋白， 特别是钴卟啉取代的肌红蛋白和血红蛋白将 以及它们的相互作用模式， 如氧气、一氧化碳和一氧化二氮，将由 热力学和动力学测量以及光谱方法， 尤其是EPR、NMR、共振拉曼和穆斯堡尔光谱 技术. 这样的研究将使我们能够确定立体化学 电子因素影响的动力学和热力学性质， 配体相互作用，配位的相关变化， 辅基和三级和四级结构， 分子，了解可逆配体的分子机制 结合、配体活化以及配体和效应子连接的亚基 这些呼吸血红蛋白的协同性和变构性， 最终设计出人工血红素蛋白， 具有生物医学重要性的天然血红素蛋白的替代品。 因此，我们认为， 拟议的项目主要集中在生理和生物医学 组织中氧气输送和利用的重要方面。 以来 血红蛋白协同性和变构性的分子机制 这无疑为我们理解 代谢中的变构酶， 复合物经常被观察到作为代谢的中间体/副产物 含氮致癌物，拟议的项目将有广泛的 生物医学意义

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.