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A ligand-binding pocket in the dengue virus envelope glycoprotein.

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.

SUBMITTER: Modis Y

PROVIDER: S-EPMC165817 | biostudies-literature | 2003 Jun

REPOSITORIES: biostudies-literature

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A ligand-binding pocket in the dengue virus envelope glycoprotein.

Modis Yorgo Y Ogata Steven S Clements David D Harrison Stephen C SC

Proceedings of the National Academy of Sciences of the United States of America 20030520 12

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 pa ...[more]

PMID: 12759475

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