GluR2 ligand-binding core complexes: Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists

C. Kasper, M. L. Lunn, T. Liljefors, E. Gouaux, J. Egebjerg, J. S. Kastrup

Research output: Contribution to journalArticle

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Abstract

X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.

Original languageEnglish (US)
Pages (from-to)173-178
Number of pages6
JournalFEBS Letters
Volume531
Issue number2
DOIs
StatePublished - Nov 6 2002

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Keywords

  • AMPA analogue
  • Agonist
  • Ionotropic glutamate receptor
  • Ligand-binding core
  • X-ray crystallography

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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