4x48

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'''Unreleased structure'''
 
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The entry 4x48 is ON HOLD until Paper Publication
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==Crystal structure of GluR2 ligand-binding core==
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<StructureSection load='4x48' size='340' side='right'caption='[[4x48]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4x48]] 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=4X48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X48 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]] 1.89&#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=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=XPF:N-{(3S,4S)-4-[4-(5-CYANOTHIOPHEN-2-YL)PHENOXY]TETRAHYDROFURAN-3-YL}PROPANE-2-SULFONAMIDE'>XPF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4x48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x48 OCA], [https://pdbe.org/4x48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x48 RCSB], [https://www.ebi.ac.uk/pdbsum/4x48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x48 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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A unique tetrahydrofuran ether class of highly potent alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmented by converting it to a conformationally constrained tetrahydrofuran to improve key interactions with the human GluA2 ligand-binding domain. Subsequent replacement of the distal phenyl motif with 2-cyanothiophene to enhance its potency, selectivity and metabolic stability afforded N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfona mide (PF-04958242, 3), whose preclinical characterization suggests an adequate therapeutic index, aided by low projected human oral pharmacokinetic variability, for clinical studies exploring its ability to attenuate cognitive deficits in patients with schizophrenia.
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Authors: Pandit, J.
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The Discovery and Characterization of the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Potentiator N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfona mide (PF-04958242).,Shaffer CL, Patel NC, Schwarz JB, Scialis RJ, Wei Y, Hou XJ, Xie L, Karki K, Bryce D, Osgood SM, Hoffmann WE, Lazzaro JT, Chang C, McGinnis DF, Lotarski SM, Liu J, Obach R, Weber ML, Chen LM, Zasadny KR, Seymour PA, Schmidt C, Hajos M, Hurst RS, Pandit J, O'Donnell CJ J Med Chem. 2015 Apr 23. PMID:25905800<ref>PMID:25905800</ref>
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Description: Crystal structure of GluR2 ligand-binding core
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4x48" style="background-color:#fffaf0;"></div>
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==See Also==
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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: Pandit J]]

Current revision

Crystal structure of GluR2 ligand-binding core

PDB ID 4x48

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