4ymb
From Proteopedia
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| - | ''' | + | ==Structure of the ligand-binding domain of GluK1 in complex with the antagonist CNG10111== |
| + | <StructureSection load='4ymb' size='340' side='right' caption='[[4ymb]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ymb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YMB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YMB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4E7:(3R,4S)-3-(3-CARBOXYPHENYL)-4-PROPYL-L-PROLINE'>4E7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e0x|4e0x]]</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=4ymb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ymb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ymb RCSB], [http://www.ebi.ac.uk/pdbsum/4ymb PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 muM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 A resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8 degrees and 2f a domain opening in GluK1-LBD of 17.0-17.5 degrees relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate. | ||
| - | + | Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.,Krogsgaard-Larsen N, Storgaard M, Moller C, Demmer CS, Hansen J, Han L, Monrad RN, Nielsen B, Tapken D, Pickering DS, Kastrup JS, Frydenvang K, Bunch L J Med Chem. 2015 Jul 22. PMID:26200741<ref>PMID:26200741</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Frydenvang, K]] | [[Category: Frydenvang, K]] | ||
| - | [[Category: Kastrup, J | + | [[Category: Kastrup, J S]] |
[[Category: Moller, C]] | [[Category: Moller, C]] | ||
[[Category: Tapken, D]] | [[Category: Tapken, D]] | ||
| + | [[Category: Antagonist]] | ||
| + | [[Category: Fusion protein]] | ||
| + | [[Category: Ionotropic glutamate receptor]] | ||
| + | [[Category: Kainate receptor gluk1]] | ||
| + | [[Category: Ligand-binding domain]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 20:06, 5 August 2015
Structure of the ligand-binding domain of GluK1 in complex with the antagonist CNG10111
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