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

FEBS Lett. 2002 Nov 6;531(2):173-8. doi: 10.1016/s0014-5793(02)03496-8.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Isoxazoles / chemistry*
  • Ligands
  • Macromolecular Substances
  • Methionine / chemistry
  • Models, Molecular
  • Peptides / chemistry
  • Protein Binding
  • Receptors, AMPA / agonists*
  • Receptors, AMPA / chemistry*
  • Receptors, AMPA / metabolism
  • Sulfates / chemistry
  • Zinc / chemistry
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / analogs & derivatives
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / chemistry*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism*


  • 2-amino-3-(3-hydroxy-4-isoxazoyl)propionic acid
  • Isoxazoles
  • Ligands
  • Macromolecular Substances
  • Peptides
  • Receptors, AMPA
  • Sulfates
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Methionine
  • Zinc
  • glutamate receptor ionotropic, AMPA 2