6ruq: Difference between revisions

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 ==Structure of GluA2cryst in complex the antagonist ZK200775 and the negative allosteric modulator GYKI53655 at 4.65 A resolution==
-<StructureSection load='6ruq' size='340' side='right'caption='[[6ruq]]' scene=''>
+<StructureSection load='6ruq' size='340' side='right'caption='[[6ruq]], [[Resolution|resolution]] 4.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RUQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RUQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ruq]] is a 4 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=6RUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RUQ FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ruq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ruq OCA], [http://pdbe.org/6ruq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ruq RCSB], [http://www.ebi.ac.uk/pdbsum/6ruq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ruq ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GYK:(8R)-5-(4-AMINOPHENYL)-N,8-DIMETHYL-8,9-DIHYDRO-2H,7H-[1,3]DIOXOLO[4,5-H][2,3]BENZODIAZEPINE-7-CARBOXAMIDE'>GYK</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</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=6ruq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ruq OCA], [https://pdbe.org/6ruq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ruq RCSB], [https://www.ebi.ac.uk/pdbsum/6ruq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ruq 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ionotropic glutamate receptors are ligand-gated ion channels governing neurotransmission in the central nervous system. Three major types of antagonists are known for the AMPA-type receptor GluA2: competitive, non-competitive (i.e. negative allosteric modulators; NAMs) used for treatment of epilepsy, and uncompetitive antagonists. We here report a 4.65 A resolution X-ray structure of GluA2, revealing that four molecules of the competitive antagonist ZK200775 and four molecules of the NAM GYKI53655 are capable of binding at the same time. Using negative stain electron microscopy, we show that GYKI53655 alone or ZK200775/GYKI53655 in combination predominantly result in compact receptor forms. The agonist AMPA provides a mixed population of compact and bulgy shapes of GluA2 not impacted by addition of GYKI53655. Taken together, this suggests that the two different mechanisms of antagonism that lead to channel closure are independent and that the distribution between bulgy and compact receptors primarily depends on the ligand bound in the glutamate binding site.
+Binding of a negative allosteric modulator and competitive antagonist can occur simultaneously at the ionotropic glutamate receptor GluA2.,Krintel C, Dorosz J, Larsen AH, Seneca Thorsen T, Venskutonyte R, Mirza O, Gajhede M, Boesen T, Kastrup JS FEBS J. 2020 Jun 15. doi: 10.1111/febs.15455. PMID:32543078<ref>PMID:32543078</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6ruq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Rattus norvegicus]]
 [[Category: Gajhede M]]
 [[Category: Kastrup JS]]
 [[Category: Krintel C]]
 [[Category: Mirza OA]]
-[[Category: Venskutonye R]]
+[[Category: Venskutonyte R]]