排序方式: 共有5条查询结果,搜索用时 15 毫秒
1
1.
Papaconstantinou ME Gandhi PS Chen Z Bah A Di Cera E 《Cellular and molecular life sciences : CMLS》2008,65(22):3688-3697
Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na(+)-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 A resolution. The structure reveals a Na(+) binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na(+) binding to meizothrombin desF1 document a slow phase of fluorescence change with a k(obs) decreasing hyperbolically with increasing [Na(+)], consistent with the existence of three conformations in equilibrium, E*, E and E:Na(+), as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation. 相似文献
2.
G蛋白偶联受体(G protein-coupled receptor, GPCR)构成人体中最庞大的膜蛋白家族,也是最重要的一类药物靶 标。随着GPCR结构解析技术的突破,目前已破解八十余个受体的400多个结构,揭示出GPCR复杂多样的配体结合模式和 跨膜信号转导机制。近年来,残基相互作用计算已实现对GPCR构象变化的精细描述,揭示出A家族GPCR存在共同的激活 机制。文章简要回顾GPCR激活机制研究的方法和创新点,并对A家族GPCR共同激活机制如何推动功能研究和药物研发进行展望。 相似文献
3.
Serine peptidases: Classification, structure and function 总被引:1,自引:1,他引:0
Serine peptidases play key roles in human health and disease and their biochemical properties shaped the molecular evolution
of these processes. Of known proteolytic enzymes, the serine peptidase family is the major cornerstone of the vertebrate degradome.
We describe the known diversity of serine peptidases with respect to structure and function. Particular emphasis is placed
on the S1 peptidase family, the trypsins, which underwent the most predominant genetic expansion yielding the enzymes responsible
for vital processes in man such as digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis and immunity.
Received 13 December 2007; received after revision 8 January 2008; accepted 22 January 2008 相似文献
4.
5.
Coagulation factor VIIa (FVIIa) is an atypical member of the trypsin family of serine proteases. It fails to attain spontaneously
its catalytically competent conformation and requires its protein cofactor tissue factor (TF) to accomplish this. Over a number
of years, this unique behaviour of FVIIa has prompted investigations of the TF-induced activation mechanism and the zymogenicity
determinants in factor VIIa. Factor VIIa has gained additional interest in the past decade because of its development into
a clinically useful haemostatic agent. Here, we present an overview of the current knowledge about the TF-induced allosteric
activation of FVIIa and the various molecular approaches to enhance the intrinsic activity and efficacy of FVIIa.
Received 18 October 2007; received after revision 12 November 2007; accepted 14 November 2007 相似文献
1