1syh: Difference between revisions

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-[[Image:1syh.png|left|200px]]
-{{STRUCTURE_1syh|  PDB=1syh  |  SCENE=  }}
+==X-RAY STRUCTURE OF THE GLUR2 LIGAND-BINDING CORE (S1S2J) IN COMPLEX WITH (S)-CPW399 AT 1.85 A RESOLUTION.==
+<StructureSection load='1syh' size='340' side='right'caption='[[1syh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1syh]] is a 1 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=1SYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SYH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPW:(S)-2-AMINO-3-(1,3,5,7-PENTAHYDRO-2,4-DIOXO-CYCLOPENTA[E]PYRIMIDIN-1-YL)+PROIONIC+ACID'>CPW</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1syh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1syh OCA], [https://pdbe.org/1syh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1syh RCSB], [https://www.ebi.ac.uk/pdbsum/1syh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1syh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sy/1syh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1syh ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ionotropic glutamate receptors mediate most rapid excitatory synaptic transmission in the mammalian central nervous system, and their involvement in neurological diseases has stimulated widespread interest in their structure and function. Despite a large number of agonists developed so far, few display selectivity among (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA)-receptor subtypes. The present study provides X-ray structures of the glutamate receptor 2 (GluR2)-selective partial agonist (S)-2-amino-3-(1,3,5,6,7-pentahydro-2,4-dioxocyclopenta[e] pyrimidin-1-yl) propanoic acid [(S)-CPW399] in complex with the ligand-binding core of GluR2 (GluR2-S1S2J) and with a (Y702F)GluR2-S1S2J mutant. In addition, the structure of the nonselective partial agonist kainate in complex with (Y702F)GluR2-S1S2J was determined. The results show that the selectivity of (S)-CPW399 toward full-length GluR2 relative to GluR3 is reflected in the binding data on the two soluble constructs, allowing the use of (Y702F)GluR2-S1S2J as a model system for studying GluR2/GluR3 selectivity. Structural comparisons suggest that selectivity arises from disruption of a water-mediated network between ligand and receptor. A D1-D2 domain closure occurs upon agonist binding. (S)-CPW399 and kainate induce greater domain closure in the Y702F mutant, indicating that these partial agonists here act in a manner more reminiscent of full agonists. Both kainate and (S)-CPW399 exhibited higher efficacy at (Y702F)GluR2(Q)i than at wild-type GluR2(Q)i. Whereas an excellent correlation exists between domain closure and efficacy of a range of agonists at full-length GluR2 determined by electrophysiology in Xenopus laevis oocytes, a direct correlation between agonist induced domain closure of (Y702F)GluR2-S1S2J and efficacy at the GluR3 receptor is not observed. Although it clearly controls selectivity, mutation of this residue alone is insufficient to explain agonist-induced conformational rearrangements occurring in this variant.
-===X-RAY STRUCTURE OF THE GLUR2 LIGAND-BINDING CORE (S1S2J) IN COMPLEX WITH (S)-CPW399 AT 1.85 A RESOLUTION.===
+Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2.,Frandsen A, Pickering DS, Vestergaard B, Kasper C, Nielsen BB, Greenwood JR, Campiani G, Fattorusso C, Gajhede M, Schousboe A, Kastrup JS Mol Pharmacol. 2005 Mar;67(3):703-13. Epub 2004 Dec 9. PMID:15591246<ref>PMID:15591246</ref>
-{{ABSTRACT_PUBMED_15591246}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1syh" style="background-color:#fffaf0;"></div>
-[[1syh]] is a 1 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=1SYH OCA].
 ==See Also==
-*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:015591246</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Campiani, G.]]
+[[Category: Campiani G]]
-[[Category: Frandsen, A.]]
+[[Category: Frandsen A]]
-[[Category: Gajhede, M.]]
+[[Category: Gajhede M]]
-[[Category: Greenwood, J R.]]
+[[Category: Greenwood JR]]
-[[Category: Kasper, C.]]
+[[Category: Kasper C]]
-[[Category: Kastrup, J S.]]
+[[Category: Kastrup JS]]
-[[Category: Nielsen, B B.]]
+[[Category: Nielsen BB]]
-[[Category: Pickering, D S.]]
+[[Category: Pickering DS]]
-[[Category: Schousboe, A.]]
+[[Category: Schousboe A]]
-[[Category: Vestergaard, B.]]
+[[Category: Vestergaard B]]
-[[Category: Agonist complex]]
-[[Category: Ionotropic glutamate receptor glur2]]
-[[Category: Ligand-binding core]]
-[[Category: Membrane protein]]