HUMAN THROMBIN BINDING AND RECOGNITION SITES

凝血酶是血液凝固过程中的关键酶，它对健康的意义 不能低估这些问题（如循环系统疾病和中风）。 这里提出的研究有助于更详细地描述 凝血酶在分子水平上的作用作为未来的基础 药物治疗 这项研究的长期目标是了解结构， 人凝血酶在分子水平上的功能。 的具体目标 该项目将 1)制定了凝血酶活性位点及其直接 外围包括原子间距离的测量; 2)描述和表征纤维蛋白原识别位点， 表征和鉴定这些α-凝血酶区域或残基 参与纤维蛋白原结合，以及它们在非凝血性 γ-凝血酶形式。 3)检查这些特异性结合区域作为血小板受体激动剂， 凝血酶诱导血小板聚集分泌现象。 4)在分子水平上检查其他凝血酶-大分子相互作用 （水蛭素，α 2-巨球蛋白）。 这些研究将涉及生物化学学科的结合， 酶学、荧光、ESR、NMR和激光光CIDNP NMR。 α-凝血酶在止血中起着重要的生物调节作用， 主要功能是催化纤维蛋白原转化为凝块。 一 当认识到它在医学科学中的重要性时， 死亡和残疾超过癌症或其他任何疾病造成的死亡和残疾， 健康失调 很明显，理解和最终控制 凝血酶在止血中的功能是医学研究中的高度优先事项。

Thrombin is a key enzyme in blood coagulation; its significance to health problems (e.g. circulatory diseases and stroke) cannot be underestimated. The studies proposed here contribute to a more detailed description of thrombin action at the molecular level as a basis for future pharmacological therapy. The long term goals of this research are to understand the structure and function of human thrombins at the molecular level. The specific aims of this project are to 1) formulate a detailed map of the thrombin active site and its immediate periphery including the measurement in solution of interatomic distances; 2) Describe and characterize the fibrinogen recognition site by characterizing and identifying these Alpha-thrombin regions or residues involved in fibrinogen binding, and how they differ in the non-coagulant Gamma-thrombin form. 3) Examine these specific binding regions as platelet receptor agonists in thrombin induced platelet aggregation secretion phenomena. 4) Examine other thrombin-macromolecule interactions at the molecular level (hirudin, Alpha2-macroglobulin). These studies will involve the combined biochemical disciplines of enzymology, fluorescence, ESR, NMR and laser photo CIDNP NMR. Alpha-Thrombin plays a central bioregulatory role in hemostasis besides its primary function of catalyzing the conversion of fibrinogen to a clot. One cannot undervalue its importance in the medical sciences when recognizing that deaths and disabilities exceed those caused by cancer or any other health disorder. It is clear that the understanding and eventual control of thrombin function in hemostasis is a high priority in medical research.