4nwc: Difference between revisions
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==Crystal structure of the GluK3 ligand-binding domain (S1S2) in complex with the agonist (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic acid at 2.01 A resolution.== | ==Crystal structure of the GluK3 ligand-binding domain (S1S2) in complex with the agonist (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic acid at 2.01 A resolution.== | ||
<StructureSection load='4nwc' size='340' side='right' caption='[[4nwc]], [[Resolution|resolution]] 2.01Å' scene=''> | <StructureSection load='4nwc' size='340' side='right'caption='[[4nwc]], [[Resolution|resolution]] 2.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nwc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NWC OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4nwc]] 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=4NWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NWC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QE:(2S,4R)-4-(3-METHOXY-3-OXOPROPYL)+GLUTAMIC+ACID'>2QE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.012Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QE:(2S,4R)-4-(3-METHOXY-3-OXOPROPYL)+GLUTAMIC+ACID'>2QE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nwc OCA], [https://pdbe.org/4nwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nwc RCSB], [https://www.ebi.ac.uk/pdbsum/4nwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nwc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/GRIK3_RAT GRIK3_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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.<ref>PMID:21907808</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 15: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4nwc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: | [[Category: Frydenvang K]] | ||
[[Category: | [[Category: Gajhede M]] | ||
[[Category: | [[Category: Kastrup JS]] | ||
[[Category: | [[Category: Larsen AP]] | ||
[[Category: | [[Category: Venskutonyte R]] | ||
Latest revision as of 20:04, 20 September 2023
Crystal structure of the GluK3 ligand-binding domain (S1S2) in complex with the agonist (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic acid at 2.01 A resolution.Crystal structure of the GluK3 ligand-binding domain (S1S2) in complex with the agonist (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic acid at 2.01 A resolution.
Structural highlights
FunctionGRIK3_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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.[1] Publication Abstract from PubMedThe kainate receptors are the least studied subfamily of ionotropic glutamate receptors. These receptors are thought to have a neuromodulatory role and have been associated with a variety of disorders in the central nervous system. This makes kainate receptors interesting potential drug targets. Today, structures of the ligand binding domain (LBD) of the kainate receptor GluK3 are only known in complex with the endogenous agonist glutamate, the natural product kainate, and two synthetic agonists. Herein we report structures of GluK3 LBD in complex with two 2,4-syn-functionalized (S)-glutamate analogues to investigate their structural potential as chemical scaffolds. Similar binding affinities at GluK3 were determined for the 2-(methylcarbamoyl)ethyl analogue (Ki =4.0 muM) and the 2-(methoxycarbonyl)ethyl analogue (Ki =1.7 muM), in agreement with the similar positioning of the compounds within the binding pocket. As the binding affinity is similar to that of glutamate, this type of Cgamma substituent could be used as a scaffold for introduction of even larger substituents reaching into unexplored binding site regions to achieve subtype selectivity. Molecular Recognition of Two 2,4-syn-Functionalized (S)-Glutamate Analogues by the Kainate Receptor GluK3 Ligand Binding Domain.,Venskutonyte R, Larsen AP, Frydenvang K, Gajhede M, Sagot E, Assaf Z, Gefflaut T, Pickering DS, Bunch L, Kastrup JS ChemMedChem. 2014 Jul 8. doi: 10.1002/cmdc.201402204. PMID:25044437[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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