2al4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:25, 23 August 2023) (edit) (undo)
 
(11 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2al4.gif|left|200px]]
 
-
<!--
+
==CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.==
-
The line below this paragraph, containing "STRUCTURE_2al4", creates the "Structure Box" on the page.
+
<StructureSection load='2al4' size='340' side='right'caption='[[2al4]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[2al4]] is a 6 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=2AL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AL4 FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CX6:2,3,6A,7,8,9-HEXAHYDRO-11H-[1,4]DIOXINO[2,3-G]PYRROLO[2,1-B][1,3]BENZOXAZIN-11-ONE'>CX6</scene>, <scene name='pdbligand=QUS:(S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC+ACID'>QUS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
{{STRUCTURE_2al4| PDB=2al4 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2al4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2al4 OCA], [https://pdbe.org/2al4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2al4 RCSB], [https://www.ebi.ac.uk/pdbsum/2al4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2al4 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT] 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.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/al/2al4_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2al4 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been limited understanding of the molecular mechanism of action for AMPA receptor potentiators. Here we present cocrystal structures of the glutamate receptor GluR2 S1S2 ligand-binding domain in complex with aniracetam [1-(4-methoxybenzoyl)-2-pyrrolidinone] or CX614 (pyrrolidino-1,3-oxazino benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deactivation. Both potentiators bind within the dimer interface of the nondesensitized receptor at a common site located on the twofold axis of molecular symmetry. Importantly, the potentiator binding site is adjacent to the "hinge" in the ligand-binding core "clamshell" that undergoes conformational rearrangement after glutamate binding. Using rapid solution exchange, patch-clamp electrophysiology experiments, we show that point mutations of residues that interact with potentiators in the cocrystal disrupt potentiator function. We suggest that the potentiators slow deactivation by stabilizing the clamshell in its closed-cleft, glutamate-bound conformation.
-
'''CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.'''
+
Mechanism of positive allosteric modulators acting on AMPA receptors.,Jin R, Clark S, Weeks AM, Dudman JT, Gouaux E, Partin KM J Neurosci. 2005 Sep 28;25(39):9027-36. PMID:16192394<ref>PMID:16192394</ref>
-
 
+
-
 
+
-
==Overview==
+
-
Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been limited understanding of the molecular mechanism of action for AMPA receptor potentiators. Here we present cocrystal structures of the glutamate receptor GluR2 S1S2 ligand-binding domain in complex with aniracetam [1-(4-methoxybenzoyl)-2-pyrrolidinone] or CX614 (pyrrolidino-1,3-oxazino benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deactivation. Both potentiators bind within the dimer interface of the nondesensitized receptor at a common site located on the twofold axis of molecular symmetry. Importantly, the potentiator binding site is adjacent to the "hinge" in the ligand-binding core "clamshell" that undergoes conformational rearrangement after glutamate binding. Using rapid solution exchange, patch-clamp electrophysiology experiments, we show that point mutations of residues that interact with potentiators in the cocrystal disrupt potentiator function. We suggest that the potentiators slow deactivation by stabilizing the clamshell in its closed-cleft, glutamate-bound conformation.
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
2AL4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AL4 OCA].
+
</div>
 +
<div class="pdbe-citations 2al4" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Mechanism of positive allosteric modulators acting on AMPA receptors., Jin R, Clark S, Weeks AM, Dudman JT, Gouaux E, Partin KM, J Neurosci. 2005 Sep 28;25(39):9027-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16192394 16192394]
+
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
 +
*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
-
[[Category: Single protein]]
+
[[Category: Clark S]]
-
[[Category: Clark, S.]]
+
[[Category: Dudman JT]]
-
[[Category: Dudman, J T.]]
+
[[Category: Gouaux E]]
-
[[Category: Gouaux, E.]]
+
[[Category: Jin R]]
-
[[Category: Jin, R.]]
+
[[Category: Partin KM]]
-
[[Category: Partin, K M.]]
+
[[Category: Weeks AM]]
-
[[Category: Weeks, A M.]]
+
-
[[Category: Cx614]]
+
-
[[Category: Glur2]]
+
-
[[Category: Ionotropic glutamate receptor]]
+
-
[[Category: Ligand binding core]]
+
-
[[Category: Modulator]]
+
-
[[Category: Quisqualate]]
+
-
[[Category: S1s2]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:10:49 2008''
+

Current revision

CRYSTAL STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH quisqualate and CX614.

PDB ID 2al4

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2al4"
Personal tools