PRIMARY STRUCTURE OF PROTHROMBIN SS1

凝血酶原 SS1 的主要结构

• 批准号: 2217573
• 负责人: KENNETH G MANN
• 金额: $ 37.55万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2217573
• 关键词: RNA splicing; activation product; animal tissue; binding proteins; biological products; chemical binding; chimeric proteins; clotting factor; coagulation factor IX; coagulation factor V; coagulation factor VII; coagulation factor VIII; coagulation factor X; congenital blood protein disorder; enzyme complex; enzyme substrate; genetic manipulation; hemostasis; human tissue; immunochemistry; membrane activity; protein C; protein purification; protein sequence; protein structure function; prothrombin; site directed mutagenesis

Factor Va is a central cofactor in the blood clotting process. Studies of its participation with factor Xa and a membrane surface in the formation of the complex which converts prothrombin to thrombin have provided significant insights into the mechanisms by which blood clots. This mechanism is central to physiologic hemostasis, and lack of regulation results in thrombosis and the occlusive events associated with venous thrombosis, pulmonary embolism, stroke and myocardial infarction. This research program is aimed at understanding the fundamental molecular contributions of factor Va and factor VIIIa in the expressions of coagulant activity and the interactions of the various constituents within the enzymatic complexes by defining the peptide regions which are explicitly associated with various binding events. Because of recent breakthroughs which permit microchemical analysis of protein structure, the recent discovery of the total amino acid sequence of factor V by this laboratory and experience gained in the expression of the factor VIII molecule, we are in a position to provide detailed structural maps of sites of interaction in these important molecules. Insights into the structure of factor V will be explicitly evaluated and extended to structural studies on factor VIII. Peptide chemistry will be used to initially locate specific sties. Molecular biology will be used to verify and further explore sites of interaction. The full cycle of organic proof, from structural identification to resynthesis, will permit unequivical evaluation of research results. Studies of the type described in the present application will ultimately have specific applications in the development of better technology for the diagnosis and treatment of thrombotic and hemorrhagic diseases.

Va 因子是血液凝固过程中的核心辅助因子。 其与因子 Xa 和膜表面参与的研究 在将凝血酶原转化为复合物的形成过程中 凝血酶通过以下方式提供了对该机制的重要见解 哪些血液会凝结。 该机制是生理学的核心 止血，缺乏调节会导致血栓形成和 与静脉血栓形成、肺部血栓相关的闭塞事件 栓塞、中风和心肌梗塞。 本研究计划 旨在了解基本的分子贡献 凝血因子Va和VIIIa在凝血剂表达中的作用 内各成分的活动和相互作用 通过定义肽区域来构建酶复合物 与各种绑定事件显式关联。 由于 最近的突破使得蛋白质的微化学分析成为可能 结构，最近发现总氨基酸序列 本实验室对因子 V 的研究以及在该实验室中获得的经验 因子 VIII 分子的表达，我们能够 提供这些相互作用位点的详细结构图 重要分子。 深入了解因子 V 的结构将 被明确评估并扩展到结构研究 因素八。 肽化学将用于初步定位 具体的猪圈。 分子生物学将用于验证和 进一步探索互动场所。 有机全循环 从结构鉴定到再合成的证明将允许 对研究结果的明确评价。 类型研究 本申请中描述的最终将具有具体的 应用程序开发更好的技术 血栓和出血性疾病的诊断和治疗。