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A ligand-binding pocket in the dengue virus envelope glycoprotein

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2003

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National Academy of Sciences
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Modis, Y., S. Ogata, D. Clements, and S. C. Harrison. 2003. “A Ligand-Binding Pocket in the Dengue Virus Envelope Glycoprotein.” Proceedings of the National Academy of Sciences 100 (12): 6986–91. doi:10.1073/pnas.0832193100.

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Abstract

Dengue virus is an emerging global health threat. Its major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals a hydrophobic pocket lined by residues that influence the pH threshold for fusion. The pocket, which accepts a hydrophobic ligand, opens and closes through a conformational shift in a beta-hairpin at the interface between two domains. These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses.

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