CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
Acta Crystallogr D Struct Biol. 2020 Nov 1;76(Pt 11):1057-1064. doi: 10.1107/S2059798320011869. Epub 2020 Oct 13.
Neuraminidase (NA) inhibitors are one of the two major classes of antivirals available for the treatment and prevention of influenza. X-ray crystal structure determination of NA head domains and their complexes with various inhibitors are of importance for the design and optimization of anti-influenza drugs. However, the globular tetrameric properties of NA head domains may produce crystals with pathological imperfections, lattice-translocation defects, making structure determination no longer straightforward. In this report, using a crystal of the NA head domain from the Wuhan Asiatic toad influenza virus as an example, the identification and solution of this type of crystal pathology are presented. Furthermore, its underlying mechanism of formation is explored.
神经氨酸酶（NA）抑制剂是可用于治疗和预防流感的两种主要抗病毒药物之一。NA 头部结构域及其与各种抑制剂复合物的 X 射线晶体结构测定对于抗流感药物的设计和优化非常重要。然而，NA 头部结构域的球形四聚体性质可能会产生具有病理性缺陷、晶格平移缺陷的晶体，使得结构测定不再简单。在本报告中，以武汉亚洲蟾蜍流感病毒的 NA 头部结构域晶体为例，介绍了这种晶体病理学的鉴定和解决方案。此外，还探讨了其形成的潜在机制。
