ORGANIC PHOSPHATE--HEMOGLOBIN INTERACTIONS

有机磷酸盐既是底物又是变构效应物 蛋白质系统的宿主。在众多实验室的优雅研究中 已经确定了这些有机磷的生理意义 效应器、结合常数及其各自的测定 调节这些重要相互作用的能量还没有 下定决心。因为有丰富的结构和功能 关于血红蛋白的信息，它可能是最好的蛋白质系统模型 研究有机磷与大分子的相互作用。 此外，其他配体(例如，C1-、HCO3-、H+等)的参与。 使血红蛋白成为研究蛋白质配基的良好模型 一般情况下，互动。我们建议研究绑定的模式 2，3-二磷酸甘油酸酯(DPG)和人血红蛋白之间的关系 PH、温度、蛋白质浓度和氧合状态 蛋白。我们提议的研究将首次描绘出 以下是调节血红蛋白系统的重要特征： (1)血红蛋白相互作用的详细性质和机理 与有机磷酸盐和其他配体，(2)相互作用能 以及所涉及的各种分子物种的能态，以及(3) DPG的各种离子物种对 生理意义上的酸碱度范围。对这些能量的解释 各州和监管限制将提供一个重要的缺失 了解血红蛋白-配基系统的链接。这是特别的 重要的是因为正是这些能量提供了 血红蛋白功能的调节。

Organic phosphates act as both substrates and allosteric effectors for a host of protein systems. While elegant studies by numerous laboratories have established the physiological significance of these organophosphate effectors, the determination of binding constants and their respective energies which regulate these important interactions have not been determined. Since there is a wealth of structural and functional information on hemoglobin, it is, perhaps, the best model protein system to study the interactions between organophosphates and macromolecules. Moreover, the involvement of other ligands (e.g., C1-, HCO3-, H+, etc.) make hemoglobin an excellent model for the study of protein-ligand interactions in general. We propose to investigate the mode of binding between 2,3-diphosphoglycerate (DPG) and human hemoglobin as a function of pH, temperature, protein concentration, and oxygenation state of the protein. Our proposed research will delineate for the first time the following important features for the regulation of the hemoglobin system: (1) the detailed nature and mechanism of the interactions of hemoglobin with organic phosphates and other ligands, (2) the energies of interaction and energy states of the various molecular species involved, and (3) the regulatory constraints imposed by the various ionic species of DPG over the physiologically significant pH range. The elucidation of these energy states and the regulatory constraints will provide an important missing link in understanding the hemoglobin-ligand system. This is particularly important because it is these energies that provide the driving force for the regulation of hemoglobin function.