4yma

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'''Unreleased structure'''
 
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The entry 4yma is ON HOLD until Paper Publication
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==Structure of the ligand-binding domain of GluA2 in complex with the antagonist CNG10109==
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<StructureSection load='4yma' size='340' side='right'caption='[[4yma]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4yma]] is a 2 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=4YMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YMA FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.895&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4E5:(3R)-3-(3-CARBOXY-5-HYDROXYPHENYL)-L-PROLINE'>4E5</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yma OCA], [https://pdbe.org/4yma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yma RCSB], [https://www.ebi.ac.uk/pdbsum/4yma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yma ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 muM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 A resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8 degrees and 2f a domain opening in GluK1-LBD of 17.0-17.5 degrees relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.
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Authors: Moller, C., Tapken, D., Kastrup, J.S., Frydenvang, K.
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Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.,Krogsgaard-Larsen N, Storgaard M, Moller C, Demmer CS, Hansen J, Han L, Monrad RN, Nielsen B, Tapken D, Pickering DS, Kastrup JS, Frydenvang K, Bunch L J Med Chem. 2015 Jul 22. PMID:26200741<ref>PMID:26200741</ref>
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Description: Structure of the ligand-binding domain of GluA2 in complex with the antagonist CNG10109
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Frydenvang, K]]
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<div class="pdbe-citations 4yma" style="background-color:#fffaf0;"></div>
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[[Category: Kastrup, J.S]]
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[[Category: Moller, C]]
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==See Also==
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[[Category: Tapken, D]]
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*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Frydenvang K]]
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[[Category: Kastrup JS]]
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[[Category: Moller C]]
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[[Category: Tapken D]]

Current revision

Structure of the ligand-binding domain of GluA2 in complex with the antagonist CNG10109

PDB ID 4yma

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