3-DIMENSIONAL STRUCTURES OF INFLUENZA NEURAMINIDASES

本项目的目的是确定三维结构的 A型流感不同亚型的神经氨酸酶（NA）分子 病毒和神经氨酸酶分子的抗原变异体在一个 亚型 这一信息应导致对结构的精确定义， 酶的活性中心和至少一些酶的结构， 抗原位点。 两种N2神经氨酸酶的三维结构 在2.9埃的分辨率是在手， 将对这些结构进行改进， 描述流感中抗原漂移的立体化学基础。 还收集了单克隆抗体的3埃衍射数据。 N2神经氨酸酶的变体。 N9亚型神经氨酸酶的结构 将使用已经在1.9 ° C下收集的X射线衍射数据测定 晶体蛋白质的埃分辨率。 该项目旨在开发一种有效手段， 控制流感，所获得的信息将： 1. 提供了发生在过程中的精确分子变化的知识 流感病毒的抗原漂移。 2. 提供关于神经氨酸酶活性位点的准确信息 这可能会导致分子的制造， 与神经氨酸酶的酶活性中心相互作用， 病毒在体内的传播。 该项目需要流感病毒的高分辨率X射线衍射数据 神经氨酸酶 由于我们的实验室已经掌握了大部分数据， 据我们所知，没有美国实验室准备致力于此类研究 现在的时间

The aim of this project is to determine the 3-dimensional stucture of neuraminidase (NA) molecules from different subtypes of type A influenza virus and of neuraminidase molecules from antigenic variants within one subtype. This information should lead to a precise definition of the structure of the active centre of the enzyme and the structure of at least some of the antigenic sites. The three dimensional structures of two N2 neuraminidases at 2.9 angstrom resolution are in hand and separate crystallographic refinement of these structures will be undertaken to enable a first description of the stereochemical basis of antigenic drift in influenza. 3\angstrom diffraction data have also been collected for a monoclonal variant of an N2 neuraminidase. The structure of subtype N9 neuraminidase will be determined using X-ray diffraction data already collected at 1.9 angstrom resolution from crystalline protein. The project is directed toward the development of an effective means to control influenza and the information obtained will: 1. provide knowledge of the precise molecular changes which occur during antigenic drift in influenza virus. 2. provide accurate information about the active site of neuraminidase which may lead to the fabrication of molecules which will specifically interact with the enzyme active centre of the neuraminidase and stop the spread of the virus in the body. This project requires high resolution X-ray diffraction data from influenza neuraminidase. Since much of the data is already in hand in our laboratory we know of no U.S. laboratory prepared to commit itself to such a study at the present time.