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ORGANIC PHOSPHATE--HEMOGLOBIN INTERACTIONS

有机磷酸盐--血红蛋白相互作用

基本信息

批准号：
3340119
负责人：
DENNIS A POWERS
金额：
$ 9.65万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-05-01 至 1986-04-30
项目状态：
已结题

项目摘要

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.

有机磷酸盐作为底物和变构效应物，蛋白质系统的宿主。虽然许多实验室的研究已经确定了这些有机磷的生理意义效应物、结合常数的确定及其各自的调节这些重要相互作用的能量还没有被测定由于有丰富的结构和功能关于血红蛋白的信息，它也许是最好的蛋白质系统模型，研究有机磷酸酯与大分子之间的相互作用。此外，其他配体（例如，C1-、HCO 3-、H+等）使血红蛋白成为研究蛋白质-配体的极好模型一般的互动。我们建议研究结合的方式 2，3-二磷酸甘油酸（DPG）和人血红蛋白之间的关系， pH、温度、蛋白质浓度和氧化状态，蛋白我们提出的研究将首次描述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制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种类的能量状态，以及（3） DPG的各种离子种类对环境的调节约束生理上重要的pH值范围。对这些能量的解释国家和监管限制将提供一个重要的缺失，在理解血红蛋白-配体系统中的联系。这是特别重要的是，正是这些能量提供了驱动力，血红蛋白功能的调节。