|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6sbt' size='340' side='right'caption='[[6sbt]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6sbt' size='340' side='right'caption='[[6sbt]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6sbt]] 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=6SBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SBT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6sbt]] 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=6SBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SBT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L5H:~{N}-[7-imidazol-1-yl-2,3-bis(oxidanylidene)-6-(trifluoromethyl)-4~{H}-quinoxalin-1-yl]benzamide'>L5H</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Grik1, Glur5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L5H:~{N}-[7-imidazol-1-yl-2,3-bis(oxidanylidene)-6-(trifluoromethyl)-4~{H}-quinoxalin-1-yl]benzamide'>L5H</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6sbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sbt OCA], [http://pdbe.org/6sbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sbt RCSB], [http://www.ebi.ac.uk/pdbsum/6sbt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sbt ProSAT]</span></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=6sbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sbt OCA], [https://pdbe.org/6sbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sbt RCSB], [https://www.ebi.ac.uk/pdbsum/6sbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sbt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT]] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref> | + | [https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6sbt" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6sbt" 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: Large Structures]] |
| - | [[Category: Frydenvang, K]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Kastrup, J S]] | + | [[Category: Frydenvang K]] |
| - | [[Category: Moellerud, S]] | + | [[Category: Kastrup JS]] |
| - | [[Category: Antagonist]] | + | [[Category: Moellerud S]] |
| - | [[Category: Gluk1-s1s2]]
| + | |
| - | [[Category: Kainate receptor ligand-binding domain]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
GRIK1_RAT Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.[1]
Publication Abstract from PubMed
Selective pharmacological tool compounds are invaluable for understanding the functions of the various ionotropic glutamate receptor subtypes. For the kainate receptors these compounds are few. Here we have synthesized 9 novel quinoxaline-2,3-diones with substitutions in the 7-position to investigate the structure-activity relationship at kainate and AMPA receptors. Compound 11 exhibited the highest binding affinity across GluK1-3 while having a 73-fold selectivity towards kainate vs. AMPA receptors. 11 potently inhibited glutamate evoked currents at homomeric GluK1 and GluK3 receptors in HEK293 cells with Kb values of 65 and 39 nM, respectively. The binding mode of 11 in the ligand binding domain of GluK1 was investigated by X-ray crystallography, revealing that 11 stabilizes the receptor in an open conformation, consistent with its demonstrated antagonism. Furthermore, 11 was tested for analgesic effects in the mouse tail flick test where it significantly increased tail flick latency at doses where NBQX was ineffective.
N-(7-(1H-imidazol-1-yl)-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H) -yl)benzamide - a new kainate receptor selective antagonist and analgesic: Synthesis, X-ray crystallography, structure-affinity relationships, in vitro and in vivo pharmacology.,M Oslash Llerud S, Hansen RB, Pallesen JS, Temperini P, Pasini D, Bornholdt J, Nielsen B, Mamedova E, Chalupnik P, Paternain AV, Lerma J, Del Castillo MD, Andreasen JT, Frydenvang K, Kastrup JS, Johansen TN, Pickering DS ACS Chem Neurosci. 2019 Oct 17. doi: 10.1021/acschemneuro.9b00479. PMID:31622082[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mayer ML, Ghosal A, Dolman NP, Jane DE. Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. J Neurosci. 2006 Mar 15;26(11):2852-61. PMID:16540562 doi:26/11/2852
- ↑ M Oslash Llerud S, Hansen RB, Pallesen JS, Temperini P, Pasini D, Bornholdt J, Nielsen B, Mamedova E, Chalupnik P, Paternain AV, Lerma J, Del Castillo MD, Andreasen JT, Frydenvang K, Kastrup JS, Johansen TN, Pickering DS. N-(7-(1H-imidazol-1-yl)-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H) -yl)benzamide - a new kainate receptor selective antagonist and analgesic: Synthesis, X-ray crystallography, structure-affinity relationships, in vitro and in vivo pharmacology. ACS Chem Neurosci. 2019 Oct 17. doi: 10.1021/acschemneuro.9b00479. PMID:31622082 doi:http://dx.doi.org/10.1021/acschemneuro.9b00479
|
