A ligand-binding pocket in the dengue virus envelope glycoprotein
- *Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115; and †Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, HI 96701
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Contributed by Stephen C. Harrison, April 14, 2003
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 β-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.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: harrison{at}crystal.harvard.edu.
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Abbreviations: TBE, tick-borne encephalitis virus; β-OG, n-octyl-β-D-glucoside.
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Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 1OAM and 1OAN).
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See commentary on page 6899.
- Copyright © 2003, The National Academy of Sciences
