3-DIMENSIONAL STRUCTURES OF INFLUENZA NEURAMINIDASES

这个项目的目的是确定三维结构 甲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 子类型。 这些信息应该导致对结构的准确定义 酶的活性中心和至少一些 抗原性部位。两种N_2神经氨酸酶的三维结构 在2.9埃的分辨率是手头和分离的结晶学 将对这些结构进行改进，以使第一个 描述流感抗原漂移的立体化学基础。 还收集了一株单株的3埃衍射数据 一种神经氨酸酶的变种。N9亚型神经氨酸酶的结构 将使用已经在1.9收集的X射线衍射数据来确定 晶体蛋白质的埃斯特罗姆分辨率。 该项目旨在开发一种有效的手段来 控制流感，所获得的资料将： 1.提供有关在此期间发生的精确分子变化的知识 流感病毒的抗原性漂移。 2.提供有关神经氨酸酶活性部位的准确资料 这可能导致分子的制造，这种分子将特别 与神经氨酸酶的酶活性中心相互作用，阻止 病毒在体内的传播。 该项目需要高分辨率的流感X射线衍射数据。 神经氨酸酶。因为很多数据已经掌握在我们实验室里了 据我们所知，没有任何美国实验室准备致力于这样的研究 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.