A Combined NMR-Computational Study of the Interaction between Influenza Virus Hemagglutinin and Sialic Derivatives from Human and Avian Receptors on the Surface of Transfected Cells.
A Combined NMR-Computational Study of the Interaction between Influenza Virus Hemagglutinin and Sialic Derivatives from Human and Avian Receptors on the Surface of Transfected Cells.
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DOI：
10.3390/ijms19051267
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发表时间：
2018-04-24
影响因子：
5.6
通讯作者：
Tiana G
中科院分区：
文献类型：
--
作者：
Vasile F;Panigada M;Siccardi A;Potenza D;Tiana G
流感病毒血凝素的小分子抑制剂的开发可能与对抗新的大流行病毒的扩散有关。本文利用核磁共振（NMR）技术研究了两种唾液酸衍生物Neu 5Ac-α-（2，6）-Gal-β-（1-4）-GlcNAc和Neu 5Ac-α-（2，3）-Gal-β-（1-4）-GlcNAc与重组人细胞表面直接表达的血凝素的相互作用。我们分析了这些三聚体与用血凝素的H5和H1变体转染的293 T细胞的相互作用，从而在这样的现实环境中保留其天然三聚体构象。通过利用蛋白质和配体之间的磁化转移，我们获得了结合事件的证据，并确定了表位。我们分析了聚糖的构象特征与方法相结合的NMR光谱和数据驱动的分子动力学模拟，从而获得有用的信息，有效的药物设计。
The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal-β-(1–4)-GlcNAc and Neu5Ac-α-(2,3)-Gal-β-(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design.
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