3pd9: Difference between revisions
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[[ | ==X-ray structure of the ligand-binding core of GluA2 in complex with (R)-5-HPCA at 2.1 A resolution== | ||
<StructureSection load='3pd9' size='340' side='right' caption='[[3pd9]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pd9]] is a 2 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=3PD9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PD9 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HA5:(5R)-3-HYDROXY-4,5,6,7-TETRAHYDROISOXAZOLO[5,4-C]PYRIDINE-5-CARBOXYLIC+ACID'>HA5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nnp|1nnp]], [[3pd8|3pd8]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur2, Gria2, RAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pd9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pd9 RCSB], [http://www.ebi.ac.uk/pdbsum/3pd9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4) that binds to all AMPA receptor subtypes with comparable potency. Biostructural X-ray crystallographic studies of 4 and 5 reveal different binding modes of (R)-4 and (S)-5 in the GluA2 agonist binding domain. WaterMap analysis of the GluA2 and GluA4 binding pockets with (R)-4 and (S)-5 suggests that the energy of hydration sites is ligand dependent, which may explain the observed selectivity. | |||
Biostructural and Pharmacological Studies of Bicyclic Analogues of the 3-Isoxazolol Glutamate Receptor Agonist Ibotenic Acid.,Frydenvang K, Pickering DS, Greenwood JR, Krogsgaard-Larsen N, Brehm L, Nielsen B, Vogensen SB, Hald H, Kastrup JS, Krogsgaard-Larsen P, Clausen RP J Med Chem. 2010 Nov 10. PMID:21067182<ref>PMID:21067182</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: Frydenvang, K | [[Category: Frydenvang, K]] | ||
[[Category: Kastrup, J S | [[Category: Kastrup, J S]] | ||
[[Category: Agonist complex]] | [[Category: Agonist complex]] | ||
[[Category: Ionotropic glutamate receptor glua2]] | [[Category: Ionotropic glutamate receptor glua2]] | ||
[[Category: Ligand-binding core]] | [[Category: Ligand-binding core]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
Revision as of 13:50, 9 December 2014
X-ray structure of the ligand-binding core of GluA2 in complex with (R)-5-HPCA at 2.1 A resolution
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