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| | ==STRUCTURE OF THE LIGAND-BINDING DOMAIN OF THE IONOTROPIC GLUTAMATE RECEPTOR-LIKE GLUD2 IN COMPLEX WITH 7-CKA== | | ==STRUCTURE OF THE LIGAND-BINDING DOMAIN OF THE IONOTROPIC GLUTAMATE RECEPTOR-LIKE GLUD2 IN COMPLEX WITH 7-CKA== |
| - | <StructureSection load='5cc2' size='340' side='right' caption='[[5cc2]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='5cc2' size='340' side='right'caption='[[5cc2]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cc2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CC2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CC2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cc2]] 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=5CC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CC2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CKA:7-CHLOROKYNURENIC+ACID'>CKA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 2.501Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v3u|2v3u]], [[2v3t|2v3t]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CKA:7-CHLOROKYNURENIC+ACID'>CKA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Grid2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=5cc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cc2 OCA], [https://pdbe.org/5cc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cc2 RCSB], [https://www.ebi.ac.uk/pdbsum/5cc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cc2 ProSAT]</span></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=5cc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cc2 OCA], [http://pdbe.org/5cc2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cc2 RCSB], [http://www.ebi.ac.uk/pdbsum/5cc2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cc2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GRID2_RAT GRID2_RAT]] Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. | + | [https://www.uniprot.org/uniprot/GRID2_RAT GRID2_RAT] Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5cc2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5cc2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Gajhede, M]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Kastrup, J S]] | + | [[Category: Gajhede M]] |
| - | [[Category: Naur, P]] | + | [[Category: Kastrup JS]] |
| - | [[Category: Glud2]] | + | [[Category: Naur P]] |
| - | [[Category: Ionotropic glutamate receptor]]
| + | |
| - | [[Category: Ligand binding domain]]
| + | |
| - | [[Category: Nmda receptor antagonist]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GRID2_RAT Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
Publication Abstract from PubMed
The GluD2 receptor is a fundamental component of postsynaptic sites in Purkinje neurons and is required for normal cerebellar function. GluD2 and the closely related GluD1 are classified as members of the ionotropic glutamate receptor (iGluR) super-family on basis of sequence similarity, but do not bind L-glutamate. The amino acid neurotransmitter D-serine (D-Ser) is a GluD2 receptor ligand, and endogenous D-Ser signaling through GluD2 has recently been shown to regulate endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type iGluRs during synaptic plasticity in the cerebellum such as long-term depression (LTD). Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2LC), which promotes spontaneous channel activation. We identify several compounds that modulate GluD2LC, including a halogenated alanine analog as well as the kynurenic acid analog 7-chloro-4-oxo-1H-quinoline-2-carboxylic acid (7-chlorokynurenic acid; 7-CKA). By correlating thermodynamic and structural data for 7-CKA binding to the isolated GluD2 ligand binding domain (GluD2-LBD) using isothermal titration calorimetry (ITC) and X-ray protein crystallography, we find that binding of 7-CKA to GluD2-LBD differs from D-Ser by inducing an intermediate cleft-closure of the clamshell-shaped LBD. The GluD2 ligands identified here can potentially serve as a starting point for development of GluD2-selective ligands useful as tools in studies of the signaling role of the GluD2 receptor in the brain.
Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors.,Kristensen AS, Hansen KB, Naur P, Olsen L, Kurtkaya NL, Dravid SM, Kvist T, Yi F, Pohlsgaard J, Clausen RP, Gajhede M, Kastrup JS, Traynelis SF Mol Pharmacol. 2015 Dec 10. pii: mol.115.100909. PMID:26661043[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kristensen AS, Hansen KB, Naur P, Olsen L, Kurtkaya NL, Dravid SM, Kvist T, Yi F, Pohlsgaard J, Clausen RP, Gajhede M, Kastrup JS, Traynelis SF. Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors. Mol Pharmacol. 2015 Dec 10. pii: mol.115.100909. PMID:26661043 doi:http://dx.doi.org/10.1124/mol.115.100909
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