6f28: Difference between revisions
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==Crystal structure of the kainate receptor GluK3 ligand binding domain in complex with (S)-1-[2'-Amino-2'-carboxyethyl]-6-methyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-2,4(1H,3H)-dione at resolution 2.4A== | |||
<StructureSection load='6f28' size='340' side='right' caption='[[6f28]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6f28]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F28 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CG8:(2~{S})-2-azanyl-3-[6-methyl-2,4-bis(oxidanylidene)-5,7-dihydropyrrolo[3,4-d]pyrimidin-1-yl]propanoic+acid'>CG8</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6f28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f28 OCA], [http://pdbe.org/6f28 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f28 RCSB], [http://www.ebi.ac.uk/pdbsum/6f28 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f28 ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip). | |||
(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation.,Brogi S, Brindisi M, Butini S, Kshirsagar GU, Maramai S, Chemi G, Gemma S, Campiani G, Novellino E, Fiorenzani P, Pinassi J, Aloisi AM, Gynther M, Venskutonyte R, Han L, Frydenvang K, Kastrup JS, Pickering DS J Med Chem. 2018 Feb 26. doi: 10.1021/acs.jmedchem.8b00099. PMID:29451794<ref>PMID:29451794</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6f28" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Frydenvang, K]] | [[Category: Frydenvang, K]] | ||
[[Category: Kastrup, J S]] | |||
[[Category: Venskutonyte, R]] | [[Category: Venskutonyte, R]] | ||
[[Category: | [[Category: Gluk3]] | ||
[[Category: Ionotropic glutamate receptor]] | |||
[[Category: Ligand binding domain]] | |||
[[Category: Membrane protein]] | |||
Revision as of 09:38, 28 February 2018
Crystal structure of the kainate receptor GluK3 ligand binding domain in complex with (S)-1-[2'-Amino-2'-carboxyethyl]-6-methyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-2,4(1H,3H)-dione at resolution 2.4ACrystal structure of the kainate receptor GluK3 ligand binding domain in complex with (S)-1-[2'-Amino-2'-carboxyethyl]-6-methyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-2,4(1H,3H)-dione at resolution 2.4A
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 PubMedStarting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip). (S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation.,Brogi S, Brindisi M, Butini S, Kshirsagar GU, Maramai S, Chemi G, Gemma S, Campiani G, Novellino E, Fiorenzani P, Pinassi J, Aloisi AM, Gynther M, Venskutonyte R, Han L, Frydenvang K, Kastrup JS, Pickering DS J Med Chem. 2018 Feb 26. doi: 10.1021/acs.jmedchem.8b00099. PMID:29451794[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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