@article{948882f06e8e11df928f000ea68e967b,
title = "Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP",
abstract = "The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.",
author = "Nielsen, {Bettina B} and Pickering, {Darryl S} and Greenwood, {Jeremy R} and Lotte Brehm and Michael Gajhede and Arne Schousboe and Kastrup, {Jette S}",
note = "Keywords: Alanine; Animals; Cells, Cultured; Female; Isoxazoles; Ligands; Receptors, AMPA; Spodoptera; Xenopus laevis",
year = "2005",
doi = "10.1111/j.1742-4658.2005.04583.x",
language = "English",
volume = "272",
pages = "1639--48",
journal = "F E B S Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "7",
}