6hch: Difference between revisions

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-'''Unreleased structure'''
-The entry 6hch is ON HOLD  until Paper Publication
+==STRUCTURE OF GLUA2 LIGAND-BINDING DOMAIN (S1S2J-L504Y-N775S) IN COMPLEX WITH GLUTAMATE AND TDPAM01 AT 1.6 A RESOLUTION.==
+<StructureSection load='6hch' size='340' side='right'caption='[[6hch]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6hch]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HCH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HCH FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D45:6,6-(Ethane-1,2-diyl)bis(4-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine+1,1-dioxide)'>D45</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hch OCA], [http://pdbe.org/6hch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hch RCSB], [http://www.ebi.ac.uk/pdbsum/6hch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hch ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://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 ==
+The ionotropic glutamate receptor GluA2 is considered to be an attractive target for positive allosteric modulation for the development of pharmacological tools or cognitive enhancers. Here, we report a detailed structural characterization of two recently reported dimeric positive allosteric modulators, TDPAM01 and TDPAM02, with nanomolar potency at GluA2. Using X-ray crystallography, TDPAM01 and TDPAM02 were crystallized in the ligand-binding domain of the GluA2 flop isoform as well as in the flip-like mutant N775S and the preformed dimer L504Y-N775S. In all structures, one modulator molecule binds at the dimer interface with two characteristic hydrogen bonds being formed from the modulator to Pro515. Whereas the GluA2 dimers and modulator binding mode are similar when crystallized in the presence of l-glutamate, the shape of the binding site differs when no l-glutamate is present. TDPAM02 has no effect on domain closure in both apo and l-glutamate bound GluA2 dimers compared to structures without modulator.
-Authors: Laulumaa, S., Hansen, K.V., Frydenvang, K., Kastrup, J.S.
+Crystal Structures of Potent Dimeric Positive Allosteric Modulators at the Ligand-Binding Domain of the GluA2 Receptor.,Laulumaa S, Hansen KV, Masternak M, Drapier T, Francotte P, Pirotte B, Frydenvang K, Kastrup JS ACS Med Chem Lett. 2018 Nov 4;10(3):243-247. doi: 10.1021/acsmedchemlett.8b00369., eCollection 2019 Mar 14. PMID:30891120<ref>PMID:30891120</ref>
-Description: STRUCTURE OF GLUA2 LIGAND-BINDING DOMAIN (S1S2J-L504Y-N775S) IN COMPLEX WITH GLUTAMATE AND TDPAM01 AT 1.6 A RESOLUTION.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6hch" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Frydenvang, K]]
-[[Category: Kastrup, J.S]]
+[[Category: Hansen, K V]]
+[[Category: Kastrup, J S]]
 [[Category: Laulumaa, S]]
-[[Category: Hansen, K.V]]
+[[Category: Ampa receptor]]
+[[Category: Glua2]]
+[[Category: Glua2-s1s2j-l504y-n775]]
+[[Category: Ligand-binding domain]]
+[[Category: Membrane protein]]
+[[Category: Positive allosteric modulator]]
+[[Category: Signaling protein]]