TRYPANOSOMAL PHOSPHOGLYCERATE KINASE TRANSITION STATE & STRUC BASED DRUG DESIGN

我们希望使用同步辐射技术来确定 人von Willebrand因子(VWF)A1结构域的三维结构 从这个项目中获得的信息将有助于澄清 一个对正常生活至关重要的关键事件的机制和调控 止血，也参与病理性血栓形成。 目前，天然vWF的结晶被认为是不可能的 由于规模较大且具有异构性，因此可采用各种技术 分子；因此，获取3D信息的唯一途径 VWF的结构是专注于孤立的域。结果是 我们的研究将有助于定义vWF-GP Ib联系人 网站，并将协助搜索vWF的特定抑制剂 与GP Ib结合是抗血栓作用的重要靶点 干预。

We wish to use synchrotron radiation techniques to determine the 3D structure of the A1 domain of human von Willebrand factor (vWF). The information gained from this project will help clarify the mechanisms and regulation of a key event essential for normal hemostasis and also involved in pathological thrombosis. Crystallization of native vWF is considered impossible with currently available techniques due to the large size and heterogeneous nature of the molecule; thus the only approach to gain information on the 3D structure of vWF is to focus on isolated domains. The results expected from our studies will help in defining the vWF-GP Ib contact sites and will assist in searching for specific inhibitors of vWF binding to GP Ib, an important target for anti-thrombotic intervention.