View source for 3pmw


==Ligand-binding domain of GluA2 (flip) ionotropic glutamate receptor in complex with an allosteric modulator==
<StructureSection load='3pmw' size='340' side='right'caption='[[3pmw]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pmw]] 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=3PMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PMW 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=G69:N-[(2S)-5-{[4-(HYDROXYMETHYL)-3-(TRIFLUOROMETHYL)-1H-PYRAZOL-1-YL]METHYL}-2,3-DIHYDRO-1H-INDEN-2-YL]PROPANE-2-SULFONAMIDE'>G69</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3pmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pmw OCA], [https://pdbe.org/3pmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pmw RCSB], [https://www.ebi.ac.uk/pdbsum/3pmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pmw 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> 
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== Publication Abstract from PubMed ==
Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19.

Structure based evolution of a novel series of positive modulators of the AMPA receptor.,Jamieson C, Maclean JK, Brown CI, Campbell RA, Gillen KJ, Gillespie J, Kazemier B, Kiczun M, Lamont Y, Lyons AJ, Moir EM, Morrow JA, Pantling J, Rankovic Z, Smith L Bioorg Med Chem Lett. 2011 Jan 15;21(2):805-11. Epub 2010 Nov 25. PMID:21190850<ref>PMID:21190850</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3pmw" 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: Brown CI]]
[[Category: Campbell RA]]
[[Category: Gillen KJ]]
[[Category: Gillespie J]]
[[Category: Jamieson C]]
[[Category: Kazemier B]]
[[Category: Kiczun M]]
[[Category: Lamont Y]]
[[Category: Lyons AJ]]
[[Category: Maclean JKF]]
[[Category: Moir EM]]
[[Category: Morrow JA]]
[[Category: Pantling J]]
[[Category: Rankovic Z]]
[[Category: Smith L]]