A Ligand-Binding Pocket in the Dengue Virus Envelope Glycoprotein

Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91. doi: 10.1073/pnas.0832193100. Epub 2003 May 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Dengue Virus / genetics
  • Dengue Virus / metabolism*
  • Dengue Virus / pathogenicity
  • Dengue Virus / physiology
  • Dimerization
  • Humans
  • Ligands
  • Membrane Fusion
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Structure, Quaternary
  • Protein Subunits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Assembly

Substances

  • E-glycoprotein, Dengue virus type 2
  • Ligands
  • Peptide Fragments
  • Protein Subunits
  • Recombinant Proteins
  • Viral Envelope Proteins

Associated data

  • PDB/1OAM
  • PDB/1OAN