PROTEINS OF BLOOD COAGULATION

凝血蛋白

• 批准号: 2215009
• 负责人: EARL W DAVIE
• 金额: $ 120万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215009
• 关键词: blood coagulation; blood proteins; protein structure function

The long-term objective of this research program is to gain new information about the structure and function of the various proteins that participate in blood coagulation as well as their biosynthesis and regulation. In the work proposed in the present grant, considerable emphasis will be placed on the study of human fibrinogen, including: 1) the mechanism by which it is assembled from the alpha, beta and gamma chains; 2) an examination of important regions in the molecule involved in polymerization, calcium binding, leukocyte adhesion, factor XIII binding, and the role of the extended alpha chain, and; 3) a study of the 5' regulatory region of the genes coding for the alpha and gamma chains. A second goal will be to focus on the mechanism of regulation for the gene coding for factor X. Three regulatory segments in the promoter region of the factor X gene have been identified and attempts will be made to isolate and clone these regulatory proteins. Another goal of this project is to establish the location of the disulfide bonds in the heavy and light chains of recombinant factor VIII and to determine the binding sites within factor VIII for factor IXa and factor X. An additional project proposed in this application will be to clarify the role of a metalloprotease isolated in our lab as well as furin in the processing of the proportion of the vitamin K-dependent proteins. Attempts will also be made to isolate other proteases that may be important in this processing step. Another goal of this project will be to carry out crystallographic studies of mutant forms of the "a" subunit of human factor XIII. Particular emphasis will be placed on structural determination of mutations in the apparent catalytic site of the enzyme. Lastly, experiments are proposed to study the genes coding for the prostate specific antigen and human glandular kallikrein and how they are regulated in the prostate.

该研究计划的长期目标是获得新的 有关各种蛋白质的结构和功能的信息 参与血液凝血以及它们的生物合成和 规定。 在本赠款中提出的工作中，相当多 重点将放在人类纤维蛋白原的研究上，包括：1） 从Alpha，Beta和Gamma组装的机制 链2）检查参与分子中的重要区域 聚合，钙结合，白细胞粘附，因子XIII结合， 以及扩展的α链的作用，以及； 3）对5'的研究 编码α和伽马链的基因的调节区域。 一个 第二个目标是专注于基因调节机制 编码因子X。在启动子区域的三个调节段 已经确定了因子X基因并将尝试 分离并克隆这些调节蛋白。 这个项目的另一个目标 是在重和光线中建立二硫键的位置 重组因子VIII的链并确定结合位点 在因子IXA和X因子VIII中。另一个项目 在本应用中提出的建议是阐明 在我们的实验室中孤立的金属蛋白酶以及在处理中的脂蛋白 维生素K依赖性蛋白的比例。 尝试也将是 制造了在此处理中可能很重要的其他蛋白酶 步。 该项目的另一个目标是进行晶体学 人为因素XIII的“ A”亚基的突变形式的研究。 特别重点将放在结构上的确定 酶的明显催化位点突变。 最后， 提出了实验来研究编码前列腺的基因 特定的抗原和人腺kallikrein及其如何调节 在前列腺中。