HUMAN THROMBIN BINDING AND RECOGNITION SITES

凝血酶是凝血的关键酶；它对健康的意义 问题(如循环系统疾病和中风)不能被低估。 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是未来研究的基础 药物疗法。 这项研究的长期目标是理解结构和 人凝血酶在分子水平上的功能。的具体目标 这个项目是为了 1)绘制凝血酶活性部位的详细地图及其直接 外围包括原子间距离的溶液测量； 2)通过以下方式描述和表征纤维蛋白原识别部位 鉴定和鉴定这些α-凝血酶区域或残基 参与纤维蛋白原结合，以及它们在非凝血剂中的不同之处 伽马-凝血酶形式。 3)检查这些作为血小板受体激动剂的特定结合区域 凝血酶诱导的血小板聚集分泌现象。 4)在分子水平上考察凝血酶与大分子的其他相互作用 (水蛭素、α2-巨球蛋白)。 这些研究将涉及以下生物化学学科的组合 酶学、荧光、电子自旋共振、核磁共振和激光照相CIDNP核磁共振。 α-凝血酶在止血中起着重要的生物调节作用 催化纤维蛋白原转化为凝块的主要功能。一 当认识到它在医学中的重要性时，不能低估它的重要性 死亡和残疾超过了癌症或任何其他原因 健康障碍。很明显，理解和最终的控制 凝血酶在止血中的作用一直是医学研究的重点。

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.