1WVJ

Exploring the GluR2 ligand-binding core in complex with the bicyclic AMPA analogue (S)-4-AHCP

Summary for 1WVJ

• Entry DOI: 10.2210/pdb1wvj/pdb
• Related: 1FTJ 1FTM 1M5B
• Descriptor: ionotropic glutamate receptor 2, SULFATE ION, 3-(3-HYDROXY-7,8-DIHYDRO-6H-CYCLOHEPTA[D]ISOXAZOL-4-YL)-L-ALANINE, ... (5 entities in total)
• Functional Keywords: ionotropic glutamate receptor glur2, ligand-binding core, complex with bicyclic ampa analogue, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 1
• Total formula weight: 29928.33

Authors

Nielsen, B.B.,Pickering, D.S.,Greenwood, J.R.,Brehm, L.,Gajhede, M.,Schousboe, A.,Kastrup, J.S. (deposition date: 2004-12-15, release date: 2005-04-26, Last modification date: 2024-10-23)

Primary citation

Nielsen, B.B.,Pickering, D.S.,Greenwood, J.R.,Brehm, L.,Gajhede, M.,Schousboe, A.,Kastrup, J.S.
Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP
FEBS J., 272:1639-1648, 2005

PubMed 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.

PubMed: 15794751
DOI: 10.1111/j.1742-4658.2005.04583.x

Experimental method

X-RAY DIFFRACTION (1.75 Å)