View source for 5jty


==Glutamate- and DCKA-bound GluN1/GluN2A agonist binding domains with MPX-007==
<StructureSection load='5jty' size='340' side='right'caption='[[5jty]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jty]] is a 2 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=5JTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JTY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2JK:4-HYDROXY-5,7-DIMETHYLQUINOLINE-2-CARBOXYLIC+ACID'>2JK</scene>, <scene name='pdbligand=6ND:5-({[(3,4-DIFLUOROPHENYL)SULFONYL]AMINO}METHYL)-6-METHYL-N-[(2-METHYL-1,3-THIAZOL-5-YL)METHYL]PYRAZINE-2-CARBOXAMIDE'>6ND</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene></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=5jty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jty OCA], [https://pdbe.org/5jty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jty RCSB], [https://www.ebi.ac.uk/pdbsum/5jty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jty ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
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== Publication Abstract from PubMed ==
NMDA receptors mediate excitatory synaptic transmission and regulate synaptic plasticity in the central nervous system, but their dysregulation is also implicated in numerous brain disorders. Here, we describe GluN2A-selective negative allosteric modulators (NAMs) that inhibit NMDA receptors by stabilizing the apo state of the GluN1 ligand-binding domain (LBD), which is incapable of triggering channel gating. We describe structural determinants of NAM binding in crystal structures of the GluN1/2A LBD heterodimer, and analyses of NAM-bound LBD structures corresponding to active and inhibited receptor states reveal a molecular switch in the modulatory binding site that mediate the allosteric inhibition. NAM binding causes displacement of a valine in GluN2A and the resulting steric effects can be mitigated by the transition from glycine bound to apo state of the GluN1 LBD. This work provides mechanistic insight to allosteric NMDA receptor inhibition, thereby facilitating the development of novel classes NMDA receptor modulators as therapeutic agents.

Structural Basis for Negative Allosteric Modulation of GluN2A-Containing NMDA Receptors.,Yi F, Mou TC, Dorsett KN, Volkmann RA, Menniti FS, Sprang SR, Hansen KB Neuron. 2016 Sep 3. pii: S0896-6273(16)30506-2. doi:, 10.1016/j.neuron.2016.08.014. PMID:27618671<ref>PMID:27618671</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jty" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Hansen KB]]
[[Category: Mou T-C]]
[[Category: Sprang SR]]