3rn8

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Revision as of 12:19, 5 August 2016

Crystal Structure of iGluR2 Ligand Binding Domain and Symmetrical Carboxyl Containing Potentiator

Structural highlights

3rn8 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1lbc, 1lb9, 1ftj, 1ftk, 1ftl, 3rnn
Gene:	GRIA2, GLUR2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRIA2_HUMAN] 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. 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. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.^[1]

Publication Abstract from PubMed

At the dimer interface of the extracellular ligand-binding domain of AMPA receptors a hydrophilic pocket is formed that is known to interact with two classes of positive allosteric modulators, represented by cyclothiazide and the ampakine CX614. Here we present structural and functional data on two new positive allosteric modulators of AMPA receptors, CMPDA and CMPDB. Crystallographic data show that these compounds bind within the modulator-binding pocket, and that substituents of each compound overlap with distinct moieties of cyclothiazide and CX614. The goals of the present study were to determine 1) the degree of modulation by CMPDA and CMPDB of AMPA receptor deactivation and desensitization; 2) whether these compounds are splice isoform-selective; and, 3) whether predictions of mechanism of action could be inferred by comparing molecular interactions between the ligand binding domain and each compound to those of cyclothiazide and CX614. CMPDB was found to be more isoform-selective than would be predicted from initial binding assays. Importantly, these new compounds are both more potent and more efficacious, and also may be more clinically relevant, than the previously described AMPA receptor modulators.

Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation.,Timm DM, Benveniste M, Weeks AM, Nisenbaum ES, Partin KM Mol Pharmacol. 2011 May 4. PMID:21543522^[2]

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

References

↑ Ward SE, Harries M, Aldegheri L, Andreotti D, Ballantine S, Bax BD, Harris AJ, Harker AJ, Lund J, Melarange R, Mingardi A, Mookherjee C, Mosley J, Neve M, Oliosi B, Profeta R, Smith KJ, Smith PW, Spada S, Thewlis KM, Yusaf SP. Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfo namide, a Novel Clinical AMPA Receptor Positive Modulator. J Med Chem. 2010 Jul 8. PMID:20614889 doi:10.1021/jm1005429
↑ Timm DM, Benveniste M, Weeks AM, Nisenbaum ES, Partin KM. Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation. Mol Pharmacol. 2011 May 4. PMID:21543522 doi:10.1124/mol.110.070243

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/3rn8"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of iGluR2 Ligand Binding Domain and Symmetrical Carboxyl Containing Potentiator==
 <StructureSection load='3rn8' size='340' side='right' caption='[[3rn8]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rn8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RN8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rn8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RN8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=RN8:3,3-BENZENE-1,4-DIYLBIS(4-CYANO-5-ETHYLTHIOPHENE-2-CARBOXYLIC+ACID)'>RN8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lbc|1lbc]], [[1lb9|1lb9]], [[1ftj|1ftj]], [[1ftk|1ftk]], [[1ftl|1ftl]], [[3rnn|3rnn]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRIA2, GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRIA2, GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3rn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rn8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rn8 RCSB], [http://www.ebi.ac.uk/pdbsum/3rn8 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=3rn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rn8 OCA], [http://pdbe.org/3rn8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rn8 RCSB], [http://www.ebi.ac.uk/pdbsum/3rn8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rn8 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 3rn8" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Timm, D E]]
 [[Category: Glutamate receptor potentiator complex]]

3rn8

From Proteopedia

Revision as of 12:19, 5 August 2016

Crystal Structure of iGluR2 Ligand Binding Domain and Symmetrical Carboxyl Containing Potentiator

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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