1n0t: Difference between revisions
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[[Image: | ==X-ray structure of the GluR2 ligand-binding core (S1S2J) in complex with the antagonist (S)-ATPO at 2.1 A resolution.== | ||
<StructureSection load='1n0t' size='340' side='right' caption='[[1n0t]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1n0t]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N0T FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AT1:(S)-2-AMINO-3-(5-TERT-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL)PROPIONIC+ACID'>AT1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ftj|1ftj]], [[1ftk|1ftk]], [[1fto|1fto]], [[1fwo|1fwo]], [[1ftm|1ftm]], [[1ftl|1ftl]], [[1gr2|1gr2]], [[1lb8|1lb8]], [[1lb9|1lb9]], [[1lbc|1lbc]], [[1m5e|1m5e]], [[1m5c|1m5c]], [[1m5d|1m5d]], [[1m5f|1m5f]], [[1mm7|1mm7]], [[1mm6|1mm6]], [[1m5b|1m5b]], [[1lbb|1lbb]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rat ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n0t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1n0t RCSB], [http://www.ebi.ac.uk/pdbsum/1n0t PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n0/1n0t_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid (ATPO) in complex with the ligand-binding core of the receptor. Comparison with the only previous structure of the ligand-binding core in complex with an antagonist, 6,7-dinitro-2,3-quinoxalinedione (DNQX) (Armstrong, N.; Gouaux, E. Neuron 2000, 28, 165-181), reveals that ATPO and DNQX stabilize an open form of the ligand-binding core by different sets of interactions. Computational techniques are used to quantify the differences between these two ligands and to map the binding site. The isoxazole moiety of ATPO acts primarily as a spacer, and other scaffolds could potentially be used. Whereas agonists induce substantial domain closures compared to the apo structure, ATPO only induces minor conformational changes. These results are consistent with the hypothesis that domain closure is related to receptor activation. To facilitate the design of novel AMPA receptor antagonists, we present a modified model of the binding site that includes key residues involved in ligand recognition. | |||
Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX.,Hogner A, Greenwood JR, Liljefors T, Lunn ML, Egebjerg J, Larsen IK, Gouaux E, Kastrup JS J Med Chem. 2003 Jan 16;46(2):214-21. PMID:12519060<ref>PMID:12519060</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]] | *[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Egebjerg, J.]] | [[Category: Egebjerg, J.]] | ||
Revision as of 20:18, 28 September 2014
X-ray structure of the GluR2 ligand-binding core (S1S2J) in complex with the antagonist (S)-ATPO at 2.1 A resolution.X-ray structure of the GluR2 ligand-binding core (S1S2J) in complex with the antagonist (S)-ATPO at 2.1 A resolution.
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIonotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid (ATPO) in complex with the ligand-binding core of the receptor. Comparison with the only previous structure of the ligand-binding core in complex with an antagonist, 6,7-dinitro-2,3-quinoxalinedione (DNQX) (Armstrong, N.; Gouaux, E. Neuron 2000, 28, 165-181), reveals that ATPO and DNQX stabilize an open form of the ligand-binding core by different sets of interactions. Computational techniques are used to quantify the differences between these two ligands and to map the binding site. The isoxazole moiety of ATPO acts primarily as a spacer, and other scaffolds could potentially be used. Whereas agonists induce substantial domain closures compared to the apo structure, ATPO only induces minor conformational changes. These results are consistent with the hypothesis that domain closure is related to receptor activation. To facilitate the design of novel AMPA receptor antagonists, we present a modified model of the binding site that includes key residues involved in ligand recognition. Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX.,Hogner A, Greenwood JR, Liljefors T, Lunn ML, Egebjerg J, Larsen IK, Gouaux E, Kastrup JS J Med Chem. 2003 Jan 16;46(2):214-21. PMID:12519060[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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