5h8s
From Proteopedia
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<StructureSection load='5h8s' size='340' side='right' caption='[[5h8s]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='5h8s' size='340' side='right' caption='[[5h8s]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5h8s]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5h8s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H8S FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5YC:7-[[ETHYL(PHENYL)AMINO]METHYL]-2-METHYL-[1,3,4]THIADIAZOLO[3,2-A]PYRIMIDIN-5-ONE'>5YC</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5YC:7-[[ETHYL(PHENYL)AMINO]METHYL]-2-METHYL-[1,3,4]THIADIAZOLO[3,2-A]PYRIMIDIN-5-ONE'>5YC</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h8f|5h8f]], [[5h8h|5h8h]], [[5h8n|5h8n]], [[5h8q|5h8q]], [[5h8r|5h8r]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h8f|5h8f]], [[5h8h|5h8h]], [[5h8n|5h8n]], [[5h8q|5h8q]], [[5h8r|5h8r]]</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=5h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h8s OCA], [http://pdbe.org/5h8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h8s RCSB], [http://www.ebi.ac.uk/pdbsum/5h8s PDBsum]</span></td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRIA2, GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h8s OCA], [http://pdbe.org/5h8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h8s RCSB], [http://www.ebi.ac.uk/pdbsum/5h8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h8s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN]] 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:20614889</ref> | [[http://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN]] 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:20614889</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | To enhance physiological function of NMDA receptors (NMDARs), we identified positive allosteric modulators (PAMs) of NMDARs with selectivity for GluN2A subunit-containing receptors. X-ray crystallography revealed a binding site at the GluN1-GluN2A dimer interface of the extracellular ligand-binding domains (LBDs). Despite the similarity between the LBDs of NMDARs and AMPA receptors (AMPARs), GluN2A PAMs with good selectivity against AMPARs were identified. Potentiation was observed with recombinant triheteromeric GluN1/GluN2A/GluN2B NMDARs and with synaptically activated NMDARs in brain slices from wild-type (WT), but not GluN2A knockout (KO), mice. Individual GluN2A PAMs exhibited variable degrees of glutamate (Glu) dependence, impact on NMDAR Glu EC50, and slowing of channel deactivation. These distinct PAMs also exhibited differential impacts during synaptic plasticity induction. The identification of a new NMDAR modulatory site and characterization of GluN2A-selective PAMs provide powerful molecular tools to dissect NMDAR function and demonstrate the feasibility of a therapeutically desirable type of NMDAR enhancement. | ||
| + | |||
| + | Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function.,Hackos DH, Lupardus PJ, Grand T, Chen Y, Wang TM, Reynen P, Gustafson A, Wallweber HJ, Volgraf M, Sellers BD, Schwarz JB, Paoletti P, Sheng M, Zhou Q, Hanson JE Neuron. 2016 Mar 2;89(5):983-99. doi: 10.1016/j.neuron.2016.01.016. Epub 2016 Feb, 11. PMID:26875626<ref>PMID:26875626</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5h8s" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Lupardus, P J]] | [[Category: Lupardus, P J]] | ||
[[Category: Wallweber, H J.A]] | [[Category: Wallweber, H J.A]] | ||
Revision as of 06:22, 18 April 2018
Structure of the human GluA2 LBD in complex with GNE3419
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Categories: Human | Lupardus, P J | Wallweber, H J.A | Glun1 | Glun2a | Nmda | Receptor | Transport protein
