5u8c
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==CRYSTAL STRUCTURE OF GLUN1/GLUN2A LIGAND-BINDING DOMAIN IN COMPLEX WITH GLYCINE AND NVP-AAM077== | |
| + | <StructureSection load='5u8c' size='340' side='right' caption='[[5u8c]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5u8c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U8C FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=84J:[(R)-{[(1S)-1-(4-BROMOPHENYL)ETHYL]AMINO}(2,3-DIHYDROXYQUINOXALIN-5-YL)METHYL]PHOSPHONIC+ACID'>84J</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5u8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8c OCA], [http://pdbe.org/5u8c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u8c RCSB], [http://www.ebi.ac.uk/pdbsum/5u8c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8c ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/NMDZ1_RAT NMDZ1_RAT]] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. Plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors.<ref>PMID:15996549</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Competitive antagonists against N-methyl-D-aspartate (NMDA) receptors have played critical roles throughout the history of neuropharmacology and basic neuroscience. There are currently numerous NMDA receptor antagonists containing a variety of chemical groups. Among those compounds, a GluN2-specific antagonist, (R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5 -yl)-methyl]-phosphonic acid (NVP-AAM077), contains a unique combination of a dioxoquinoxalinyl ring, a bromophenyl group, and a phosphono group. Here, we present the crystal structure of the isolated ligand-binding domain (LBD) of the GluN1-GluN2A NMDA receptor in complex with the GluN1 agonist glycine and the GluN2A antagonist NVP-AAM077. The structure shows placement of the dioxoquinoxalinyl ring and the phosphono group of NVP-AAM077 in the glutamate binding pocket in GluN2A and the novel interaction between the bromophenyl group and GluN1-Glu781 at the GluN1-GluN2A subunit interface. Site-directed mutagenesis of GluN1-Glu781 reduced the potency of inhibition by NVP-AAM077, thus confirming the involvement of the GluN1 subunit for binding of NVP-AAM077. The unique antagonist binding pattern shown in this study provides a novel dimension to design and create antagonists with potential therapeutic values. | ||
| - | + | Novel mode of antagonist binding in NMDA receptors revealed by the crystal structure of the GluN1-GluN2A ligand-binding domain complexed to NVP-AAM077.,Romero-Hernandez A, Furukawa H Mol Pharmacol. 2017 May 3. pii: mol.116.107912. doi: 10.1124/mol.116.107912. PMID:28468946<ref>PMID:28468946</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5u8c" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Furukawa, H]] | ||
| + | [[Category: Romero-Hernandez, A]] | ||
| + | [[Category: Glycine and nvp-aam077]] | ||
| + | [[Category: Receptor]] | ||
| + | [[Category: Transport protein]] | ||
Revision as of 15:39, 17 May 2017
CRYSTAL STRUCTURE OF GLUN1/GLUN2A LIGAND-BINDING DOMAIN IN COMPLEX WITH GLYCINE AND NVP-AAM077
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