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.

因子VA是血液凝结过程中的中央辅助因子。 研究其参与因子XA和膜表面的研究 在形成的复合物中，将凝血酶原转化为 凝血酶通过 哪些血液凝块。 这种机制是生理的核心 止血和缺乏调节会导致血栓形成和 与静脉血栓形成，肺部相关的闭塞事件 栓塞，中风和心肌梗塞。 该研究计划 旨在了解基本分子贡献 VA因子和VIIIA因子的凝结剂表达式 活动和各种成分的相互作用 通过定义肽区域的酶复合物 明确与各种绑定事件相关联。 由于 允许蛋白质微化学分析的最近突破 结构，最近发现的总氨基酸序列 该实验室的V因子V，并获得了经验 因子VIII分子的表达，我们处于 在这些中提供互动位点的详细结构图 重要分子。 对因子V结构的见解将 明确评估并扩展到有关的结构研究 因子VIII。 肽化学将最初定位 具体统治。 分子生物学将用于验证和 进一步探索相互作用的位点。 有机周期 从结构识别到重新合成的证据将允许 对研究结果的不相等评估。 研究类型 本应用程序中描述的最终将具有特定的 在开发更好的技术中的应用 血栓形成和出血性疾病的诊断和治疗。