4nf8

From Proteopedia

(Difference between revisions)

Revision as of 19:05, 4 August 2016

Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and glutamate in PEG2000MME

Structural highlights

4nf8 is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4nf4, 4nf5, 4nf6
Gene:	Grin1, Nmdar1 (Buffalo rat), Grin2a (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] [NMDE1_RAT] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.

Publication Abstract from PubMed

There has been a great level of enthusiasm to downregulate overactive N-methyl-D-aspartate (NMDA) receptors to protect neurons from excitotoxicity. NMDA receptors play pivotal roles in basic brain development and functions as well as in neurological disorders and diseases. However, mechanistic understanding of antagonism in NMDA receptors is limited due to complete lack of antagonist-bound structures for the L-glutamate-binding GluN2 subunits. Here, we report the crystal structures of GluN1/GluN2A NMDA receptor ligand-binding domain (LBD) heterodimers in complex with GluN1- and GluN2-targeting antagonists. The crystal structures reveal that the antagonists, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA), have discrete binding modes and mechanisms for opening of the bilobed architecture of GluN2A LBD compared to the agonist-bound form. The current study shows distinct ways by which the conformations of NMDA receptor LBDs may be controlled and coupled to receptor inhibition and provides possible strategies to develop therapeutic compounds with higher subtype-specificity.

Structural insights into competitive antagonism in NMDA receptors.,Jespersen A, Tajima N, Fernandez-Cuervo G, Garnier-Amblard EC, Furukawa H Neuron. 2014 Jan 22;81(2):366-78. doi: 10.1016/j.neuron.2013.11.033. PMID:24462099^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Inanobe A, Furukawa H, Gouaux E. Mechanism of partial agonist action at the NR1 subunit of NMDA receptors. Neuron. 2005 Jul 7;47(1):71-84. PMID:15996549 doi:10.1016/j.neuron.2005.05.022
↑ Jespersen A, Tajima N, Fernandez-Cuervo G, Garnier-Amblard EC, Furukawa H. Structural insights into competitive antagonism in NMDA receptors. Neuron. 2014 Jan 22;81(2):366-78. doi: 10.1016/j.neuron.2013.11.033. PMID:24462099 doi:http://dx.doi.org/10.1016/j.neuron.2013.11.033

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nf8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and glutamate in PEG2000MME==
 <StructureSection load='4nf8' size='340' side='right' caption='[[4nf8]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nf4|4nf4]], [[4nf5|4nf5]], [[4nf6|4nf6]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Grin1, Nmdar1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Grin2a ([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=4nf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nf8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nf8 RCSB], [http://www.ebi.ac.uk/pdbsum/4nf8 PDBsum]</span></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=4nf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nf8 OCA], [http://pdbe.org/4nf8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nf8 RCSB], [http://www.ebi.ac.uk/pdbsum/4nf8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nf8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4nf8" style="background-color:#fffaf0;"></div>
 ==See Also==

4nf8

From Proteopedia

Revision as of 19:05, 4 August 2016

Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and glutamate in PEG2000MME

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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