Download MendeleyGluR2 ligand-binding core complexes: Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists.
Kasper, C., Lunn, M.L., Liljefors, T., Gouaux, E., Egebjerg, J., Kastrup, J.S.(2002) FEBS Lett 531: 173-178
- PubMed: 12417307
- DOI: https://doi.org/10.1016/s0014-5793(02)03496-8
- Primary Citation of Related Structures:
1MQD, 1MS7 - PubMed 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.
Organizational Affiliation:
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, Copenhagen, Denmark.
