HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD

血红素蛋白在各种各样的生物中发挥着积极的作用 通过执行所选功能的基本过程。然而， 对各种血红素蛋白的氧气供应不足是导致人类 死亡率和畸形。在这项工作中，血红素蛋白是 氧转运单体和四聚体血红蛋白的研究进展 分别从果蝇和牛到氧气还原 鲨鱼和牛的单体和二聚体细胞色素C氧化酶， 分别进行了分析。对于这些系统，配基识别导致特异性 血红素-配基反应。在溶液中，蛋白质配基是如何 氧(O2)、一氧化碳(CO)和 一氧化氮(NO)与蛋白质和生色团结构的关系 动力学、环境和配体取向仍然是一个悬而未决的领域 有问题。这些条件对于理解相互作用很重要 血红素蛋白与O2、CO和NO之间的关系 功能多样化。控制属性的标识 配体的选择将为合成和开发提供支持 人造氧气载体。结构-功能的阐明 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-配基复合体。使用我们的纳秒时间分辨率 红外光谱(TRIR)、配体取向和动力学 下定决心。将使用共振拉曼光谱和傅里叶变换红外光谱来鉴定 生色团结构和配体-金属同位素振动。这个 频率(即nuco、nuFE-C和deltaFeCO)将用于计算 实验中的“G决定同位素比”(GDIR)，而TRIR 将使用线性二色性来确定角度配体的取向 相对于血红素平面法线。对于血红素蛋白质和它们的 构象，实验的GDIR和配位角将与 作为配位体角度函数计算的理论GDIR曲线图。 通过比较可以区分金属-配体的取向 (即线性、弯曲、倾斜或扭结)在血红素蛋白溶液中。这个 我们方法的独特之处在于结合了TRIR、RR、 FTIR、GDIR及单体、二聚体和四聚体血红素蛋白的研究 在溶液配基定位和选择过程中。

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.