HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD

血红素蛋白在多种生物学作用中起着积极的作用。 通过执行选定的功能来执行基本流程。 然而，在这方面， 对各种血红素蛋白供氧不足是人类 死亡率和畸形率 在这项工作中，血红素蛋白是 研究从氧转运单体和四聚体血红蛋白 从Lucina pectinata和牛，分别为氧还原 来自鲨鱼和牛的单体和二聚体细胞色素C氧化酶， 分别 对于这些系统，配体识别导致特异性 血红素配体反应 在溶液中，蛋白质配体如何 氧（O2）、一氧化碳（CO）的选择和配体亲和力， 一氧化氮（NO）与蛋白质和发色团结构相关 动力学、环境和配体取向仍然是未解决的领域 问题 这些条件对于理解 血红素蛋白质和O2，CO和NO之间，当他们进行他们的 多样化的功能。 确定控制 配体选择将为合成和开发提供支持 人造氧气载体。 结构-功能解析 单体、二聚体和四聚体血红素蛋白的关系需要 的静态和动态行为的详细知识， 血红素-蛋白质-配体复合物 利用我们的纳秒时间分辨 红外光谱（TRIR），配体取向和动力学将 测定 将采用共振拉曼和傅立叶变换红外光谱来鉴别 发色团结构和配体金属同位素振动。 的 频率（即nuCO、nuFE-C和deltaFeCO）将用于计算 实验性的“G决定簇同位素比率”（GTRIR），而TRIR 线性二色性将用于确定角配体取向 相对于血红素平面法线。 对于血红素蛋白及其 构象，实验甘精胰岛素和配体角将与 作为配体角的函数计算的理论GdR图。 比较将允许区分金属配体取向 (i.e.线性、弯曲、倾斜或扭结）。 的 我们方法的独特之处在于TRIR，rR， FTIR，甘精胰岛素和单体，二聚体和四聚体血红素蛋白研究 在溶液配体取向和选择过程中。

Heme proteins play an active role within a wide variety of biologically fundamental processes by carrying out selected functions. However, inadequate oxygen supply to various heme-proteins is a cause of human mortality and abnormalities. In this work, the heme-proteins to be studied extend from oxygen transport monomeric and tetrameric hemoglobins from Lucina pectinata and bovine, respectively, to oxygen reduction monomeric and dimeric cytochrome c oxidase from shark and bovine, respectively. For these systems ligand recognition leads to specific heme-ligand reactions. In solution, the details of how protein ligand selection and ligand affinity of oxygen (O2), carbon monoxide (CO), and nitric oxide (NO) correlate with protein and chromophore structural dynamics, environment and ligand orientation remains an area of unsolved problems. These conditions are important to understand the interaction between heme-proteins and O2, CO and NO when they carry out their diversified functions. The identification of properties which control ligand selection will provide support in the synthesis and development of artificial oxygen carriers. Elucidation of the structure-function relationship for monomeric, dimeric and tetrameric heme-proteins requires detailed knowledge of both the static and the dynamical behavior of the heme-protein-ligand complexes. Using our nanosecond time-resolved infrared spectroscopy (TRIR), ligands orientation and dynamics will e determined. Resonance Raman and FTIR will be employed to identify chromophore structure and ligand-metal isotopic vibrations. The frequencies (i.e. nuCO, nuFE-C and deltaFeCO) will be used to calculate the experimental "G determinant isotopic ration," (GDIR), while TRIR linear dichroism will be used to determine the angle ligand orientation relative to the heme plane normal. For the heme-proteins and their conformers, the experimental GDIR and ligand angles will be compared with plots of theoretical GDIR calculated as function of the ligand angle. The comparison will allow to distinguish the metal-ligand orientation (i.e. linear, bent, tilted or kinked) in heme-protein solutions. The unique aspects of our approach resides in the combination of TRIR, rR, FTIR, GDIR and monomeric, dimeric and tetrameric heme-proteins to study in solution ligand orientation ad selections process.