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<StructureSection load='2xxh' size='340' side='right' caption='[[2xxh]], [[Resolution|resolution]] 1.50Å' scene=''> | ==Crystal structure of 1-(4-(2-oxo-2-(1-pyrrolidinyl)ethyl)phenyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 1.5A resolution.== | ||
<StructureSection load='2xxh' size='340' side='right'caption='[[2xxh]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xxh]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2xxh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XXH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NG:1-{4-[2-OXO-2-(1-PYRROLIDINYL)ETHYL]PHENYL}-3-(+TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOLE'>1NG</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NG:1-{4-[2-OXO-2-(1-PYRROLIDINYL)ETHYL]PHENYL}-3-(+TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOLE'>1NG</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xxh OCA], [https://pdbe.org/2xxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xxh RCSB], [https://www.ebi.ac.uk/pdbsum/2xxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xxh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 17: | Line 16: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2xxh" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[ | *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Aldegheri | [[Category: Aldegheri L]] | ||
[[Category: Austin | [[Category: Austin NE]] | ||
[[Category: Ballantine | [[Category: Ballantine S]] | ||
[[Category: Ballini | [[Category: Ballini E]] | ||
[[Category: Bax | [[Category: Bax BD]] | ||
[[Category: Bradley | [[Category: Bradley DM]] | ||
[[Category: Clarke | [[Category: Clarke BP]] | ||
[[Category: | [[Category: DalNegro G]] | ||
[[Category: Harries | [[Category: Harries M]] | ||
[[Category: Harris | [[Category: Harris AJ]] | ||
[[Category: Harrison | [[Category: Harrison SA]] | ||
[[Category: Melarange | [[Category: Melarange RA]] | ||
[[Category: Mookherjee | [[Category: Mookherjee C]] | ||
[[Category: Mosley | [[Category: Mosley J]] | ||
[[Category: Oliosi | [[Category: Oliosi B]] | ||
[[Category: Smith | [[Category: Smith KJ]] | ||
[[Category: Thewlis | [[Category: Thewlis KM]] | ||
[[Category: Ward | [[Category: Ward SE]] | ||
[[Category: Woollard | [[Category: Woollard PM]] | ||
[[Category: Yusaf | [[Category: Yusaf SP]] | ||
Latest revision as of 04:31, 21 November 2024
Crystal structure of 1-(4-(2-oxo-2-(1-pyrrolidinyl)ethyl)phenyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 1.5A resolution.Crystal structure of 1-(4-(2-oxo-2-(1-pyrrolidinyl)ethyl)phenyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 1.5A resolution.
Structural highlights
Publication Abstract from PubMedA novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and efficacy profiles, leading to identification of a clinical candidate. Unusually for an ion channel target, this optimization was integrated with regular generation of ligand-bound crystal structures and uncovered a novel chemotype with a unique and highly conserved mode of interaction via a trifluoromethyl group. Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of AMPA Receptor Positive Allosteric Modulators.,Ward SE, Harries M, Aldegheri L, Austin NE, Ballantine S, Ballini E, Bradley DM, Bax BD, Clarke BP, Harris AJ, Harrison SA, Melarange RA, Mookherjee C, Mosley J, Dal Negro G, Oliosi B, Smith KJ, Thewlis KM, Woollard PM, Yusaf SP J Med Chem. 2010 Dec 3. PMID:21128618[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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