Air G M, Laver W G
Department of Microbiology, University of Alabama, Birmingham 35294.
Proteins. 1989;6(4):341-56. doi: 10.1002/prot.340060402.
It is the enzyme neuraminidase, projecting from the surface of influenza virus particles, which allows the virus to leave infected cells and spread in the body. Antibodies which inhibit the enzyme limit the infection, but antigenic variation of the neuraminidase renders it ineffective in a vaccine. This article describes the crystal structure of influenza virus neuraminidase, information about the active site which may lead to development of specific and effective inhibitors of the enzyme, and the structure of epitopes (antigenic determinants) on the neuraminidase. The 3-dimensional structure of the epitopes was obtained by X-ray diffraction methods using crystals of neuraminidase complexed with monoclonal antibody Fab fragments. Escape mutants, selected by growing virus in the presence of monoclonal antibodies to the neuraminidase, possess single amino acid sequence changes. The crystal structure of two mutants showed that the change in structure was restricted to that particular sidechain, but the change in the epitope was sufficient to abolish antibody binding even though it is known in one case that 21 other amino acids on the neuraminidase are in contact with the antibody.
从流感病毒颗粒表面伸出的神经氨酸酶，使病毒能够离开受感染细胞并在体内传播。抑制该酶的抗体可限制感染，但神经氨酸酶的抗原变异使其在疫苗中失效。本文描述了流感病毒神经氨酸酶的晶体结构、可能导致开发该酶特异性有效抑制剂的活性位点信息以及神经氨酸酶上抗原表位（抗原决定簇）的结构。抗原表位的三维结构通过X射线衍射方法获得，使用的是与单克隆抗体Fab片段复合的神经氨酸酶晶体。通过在针对神经氨酸酶的单克隆抗体存在下培养病毒筛选出的逃逸突变体，具有单个氨基酸序列变化。两个突变体的晶体结构表明，结构变化仅限于该特定侧链，但抗原表位的变化足以消除抗体结合，尽管在一个案例中已知神经氨酸酶上的其他21个氨基酸与抗体接触。
