3-DIMENSIONAL STRUCTURES OF INFLUENZA NEURAMINIDASES

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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.