2al4: Difference between revisions

Revision as of 18:40, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2al4.png

Template:STRUCTURE 2al4

CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.

Template:ABSTRACT PUBMED 16192394

About this StructureAbout this Structure

2AL4 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

Mechanism of positive allosteric modulators acting on AMPA receptors., Jin R, Clark S, Weeks AM, Dudman JT, Gouaux E, Partin KM, J Neurosci. 2005 Sep 28;25(39):9027-36. PMID:16192394

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.'''
+===CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.===
-==Overview==
+<!--
-Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been limited understanding of the molecular mechanism of action for AMPA receptor potentiators. Here we present cocrystal structures of the glutamate receptor GluR2 S1S2 ligand-binding domain in complex with aniracetam [1-(4-methoxybenzoyl)-2-pyrrolidinone] or CX614 (pyrrolidino-1,3-oxazino benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deactivation. Both potentiators bind within the dimer interface of the nondesensitized receptor at a common site located on the twofold axis of molecular symmetry. Importantly, the potentiator binding site is adjacent to the "hinge" in the ligand-binding core "clamshell" that undergoes conformational rearrangement after glutamate binding. Using rapid solution exchange, patch-clamp electrophysiology experiments, we show that point mutations of residues that interact with potentiators in the cocrystal disrupt potentiator function. We suggest that the potentiators slow deactivation by stabilizing the clamshell in its closed-cleft, glutamate-bound conformation.
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+{{ABSTRACT_PUBMED_16192394}}
 ==About this Structure==
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 [[Category: Quisqualate]]
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