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| | ==Crystal structure of the kainate receptor GluK3 ligand-binding domain in complex with the agonist ZA302== | | ==Crystal structure of the kainate receptor GluK3 ligand-binding domain in complex with the agonist ZA302== |
| - | <StructureSection load='4igr' size='340' side='right' caption='[[4igr]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='4igr' size='340' side='right'caption='[[4igr]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4igr]] 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=4IGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IGR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4igr]] 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=4IGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IGR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZA:(4R)-4-{3-[HYDROXY(METHYL)AMINO]-3-OXOPROPYL}-L-GLUTAMIC+ACID'>3ZA</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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ZA:(4R)-4-{3-[HYDROXY(METHYL)AMINO]-3-OXOPROPYL}-L-GLUTAMIC+ACID'>3ZA</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3s9e|3s9e]], [[4igt|4igt]]</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=4igr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4igr OCA], [https://pdbe.org/4igr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4igr RCSB], [https://www.ebi.ac.uk/pdbsum/4igr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4igr ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur7, Grik3 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4igr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4igr OCA], [http://pdbe.org/4igr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4igr RCSB], [http://www.ebi.ac.uk/pdbsum/4igr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4igr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4igr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4igr" 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: Frydenvang, K]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Gajhede, M]] | + | [[Category: Frydenvang K]] |
| - | [[Category: Kastrup, J S]] | + | [[Category: Gajhede M]] |
| - | [[Category: Larsen, A P]] | + | [[Category: Kastrup JS]] |
| - | [[Category: Venskutonyte, R]] | + | [[Category: Larsen AP]] |
| - | [[Category: Agonist]]
| + | [[Category: Venskutonyte R]] |
| - | [[Category: Ionotropic glutamate receptor]]
| + | |
| - | [[Category: Kainate receptor]]
| + | |
| - | [[Category: Ligand-binding domain]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
In the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound.
Chemoenzymatic Synthesis of New 2,4-syn-Functionalized (S)-Glutamate Analogues and Structure-Activity Relationship Studies at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters.,Assaf Z, Larsen AP, Venskutonyte R, Han L, Abrahamsen B, Nielsen B, Gajhede M, Kastrup JS, Jensen AA, Pickering DS, Frydenvang K, Gefflaut T, Bunch L J Med Chem. 2013 Feb 15. PMID:23414088[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Venskutonyte R, Frydenvang K, Gajhede M, Bunch L, Pickering DS, Kastrup JS. Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate. J Struct Biol. 2011 Sep 1. PMID:21907808 doi:10.1016/j.jsb.2011.08.014
- ↑ Assaf Z, Larsen AP, Venskutonyte R, Han L, Abrahamsen B, Nielsen B, Gajhede M, Kastrup JS, Jensen AA, Pickering DS, Frydenvang K, Gefflaut T, Bunch L. Chemoenzymatic Synthesis of New 2,4-syn-Functionalized (S)-Glutamate Analogues and Structure-Activity Relationship Studies at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters. J Med Chem. 2013 Feb 15. PMID:23414088 doi:http://dx.doi.org/10.1021/jm301433m
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