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

Research output: Contribution to journalJournal articleResearchpeer-review

C Kasper, M-L Lunn, T Liljefors, E Gouaux, J Egebjerg, Jette Sandholm Jensen Kastrup

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
JournalF E B S Letters
Volume531
Issue number2
Pages (from-to)173-8
Number of pages6
ISSN0014-5793
Publication statusPublished - 6 Nov 2002

    Research areas

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

ID: 44729582