BLOOD COAGULATION PROTEIN-METAL ION-LIPID INTERACTIONS

磷脂微囊相互作用方式的阐明 膜模型，包括金属离子和各种凝血蛋白，以及 这些相互作用导致酵素激活的方式，这些酵素 参与血栓的形成一直是一个长期的目标 这个实验室的。为了继续开发这一地区，我们将确定 单价和二价阳离子结合部位相互作用的方式 相互作用的，与活化蛋白C中的活性部位相互作用的；酶 这是一种有效的抗凝血剂。身体上和身体上的强大结合 将使用核磁共振和电子顺磁共振等化学技术来解决这些问题 问题，这些问题将通过准备和 具有高度特异性的化学试剂、单抗、 标记和鉴定参与ITS的蛋白质部分 功能繁多。将利用一种形式的蛋白质C， “Gla-Domainless”-蛋白C，它缺乏许多阳离子结合部位。 天然蛋白C，以评估其结构与功能的关系 蛋白。类似的研究将在凝血因子方面进行。 IX和X。 由多蛋白复合体激活的X因子，也包含 钙和磷脂是血液凝结的中心事件。在……里面 为了确定这一过程的机制，我们将调查 物理和运动学上的条件，在此条件下最佳激活 发生。这些办法将再次通过筹备工作和 可抑制或加速的单抗的特性 进程中的某些步骤，确定这些步骤将极大地帮助 我们对这个系统的理解。 目前，人们对控制的因素非常感兴趣 血栓和止血及其在生化水平上的阐明 肯定会向公众提出操纵这个系统的手段 人类的优势。

The elucidation of the mode of interaction of phospholipid vesicles, as membrane models, with metal ions, and various coagulation proteins, and the manner in which these interactions lead to activation of zymogens which participate in formation of the blood clot has been a long-term objective of this laboratory. To continue to develop this area, we will determine the manner in which monovalent and divalent cation binding sites interact with each other and with the active site in activated protein C; an enzyme which is a potent anticoagulant. A powerful combination of physical and chemical techniques, such as NMR and EPR, will be employed to address these questions, and these will be extended by the preparation and characterization of highly specific chemical agents, monoclonal antibodies, to label and identify the portion of the protein which is involved in its many functions. Advantage will be taken of a form of protein C, "Gla-domainless"-protein C, which lacks many of the cation binding sites of native protein C, to assess structure-function relationships of this protein. Similar studies will be conducted with blood coagulation Factors IX and X. The activation of Factor X, by a multi-protein complex, also containing calcium and phospholipid, is a central event in the clotting of blood. In order to define the mechanism of this process, we will investigate conditions, both physically and kinetically, under which optimal activation occurs. These approaches will again be extended by the preparation and characterization of monoclonal antibodies, which may inhibit or accelerate certain steps in the process, the identification of which will greatly aid our understanding of this system. There is currently a great deal of interest in the factors which control thrombosis and hemostasis and their elucidation at the biochemical level will certainly suggest means of manipulation of this system to the advantage of man.