2wky

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[[Image:2wky.png|left|200px]]
 
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==Crystal structure of the ligand-binding core of GluR5 in complex with the agonist 4-AHCP==
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The line below this paragraph, containing "STRUCTURE_2wky", creates the "Structure Box" on the page.
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<StructureSection load='2wky' size='340' side='right'caption='[[2wky]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2wky]] 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=2WKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WKY FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.2&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IBC:3-(3-HYDROXY-7,8-DIHYDRO-6H-CYCLOHEPTA[D]ISOXAZOL-4-YL)-L-ALANINE'>IBC</scene></td></tr>
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{{STRUCTURE_2wky| PDB=2wky | SCENE= }}
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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=2wky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wky OCA], [https://pdbe.org/2wky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wky RCSB], [https://www.ebi.ac.uk/pdbsum/2wky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wky ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wk/2wky_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=2wky ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The design, synthesis, and pharmacological characterization of a highly potent and selective glutamate GluR5 agonist is reported. (S)-2-Amino-3-((RS)-3-hydroxy-8-methyl-7,8-dihydro-6H-cyclohepta[d]isoxazo l-4-yl)propionic acid (5) is the 8-methyl analogue of (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propion ic acid ((S)-4-AHCP, 4). Compound 5 displays an improved selectivity profile compared to 4. A versatile stereoselective synthetic route for this class of compounds is presented along with the characterization of the binding affinity of 5 to ionotropic glutamate receptors (iGluRs). Functional characterization of 5 at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid ((S)-ATPA, 3) as previously demonstrated for 4. An X-ray crystallographic analysis of 4 and computational analyses of 4 and 5 bound to the GluR5 agonist binding domain (ABD) are presented, including a watermap analysis, which suggests that water molecules in the agonist binding site are important selectivity determinants.
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===CRYSTAL STRUCTURE OF THE LIGAND-BINDING CORE OF GLUR5 IN COMPLEX WITH THE AGONIST 4-AHCP===
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The Glutamate Receptor GluR5 Agonist (S)-2-Amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propion ic Acid and the 8-Methyl Analogue: Synthesis, Molecular Pharmacology, and Biostructural Characterization (dagger) dagger PDB ID: 2WKY .,Clausen RP, Naur P, Kristensen AS, Greenwood JR, Strange M, Brauner-Osborne H, Jensen AA, Nielsen AS, Geneser U, Ringgaard LM, Nielsen B, Pickering DS, Brehm L, Gajhede M, Krogsgaard-Larsen P, Kastrup JS J Med Chem. 2009 Jul 9. PMID:19588945<ref>PMID:19588945</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_19588945}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2wky" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19588945 is the PubMed ID number.
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{{ABSTRACT_PUBMED_19588945}}
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==About this Structure==
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[[2wky]] is a 2 chain structure of [[Ionotropic Glutamate Receptors]] 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=2WKY OCA].
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==See Also==
==See Also==
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*[[Ionotropic Glutamate Receptors]]
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*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019588945</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Gajhede, M.]]
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[[Category: Gajhede M]]
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[[Category: Kastrup, J S.]]
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[[Category: Kastrup JS]]
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[[Category: Naur, P.]]
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[[Category: Naur P]]
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[[Category: Cell junction]]
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[[Category: Cell membrane]]
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[[Category: Glycoprotein]]
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[[Category: Ion channel]]
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[[Category: Ion transport]]
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[[Category: Ionic channel]]
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[[Category: Ionotropic glutamate receptor]]
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[[Category: Ligand-binding core]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Phosphoprotein]]
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[[Category: Postsynaptic cell membrane]]
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[[Category: Receptor]]
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[[Category: Rna editing]]
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[[Category: Synapse]]
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[[Category: Transmembrane]]
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[[Category: Transport]]
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Current revision

Crystal structure of the ligand-binding core of GluR5 in complex with the agonist 4-AHCP

PDB ID 2wky

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