2xx9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:00, 1 February 2024) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2xx9.png|left|200px]]
 
-
{{STRUCTURE_2xx9| PDB=2xx9 | SCENE= }}
+
==Crystal structure of 1-((2-fluoro-4-(3-(trifluoromethyl)-4,5,6,7- tetrahydro-1H-indazol-1-yl)phenyl)methyl)-2-pyrrolidinone in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 2.2A resolution.==
 +
<StructureSection load='2xx9' size='340' side='right'caption='[[2xx9]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2xx9]] is a 3 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=2XX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XX9 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]] 1.97&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NF:N,N-DIMETHYL-4-[3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOL-1-YL]BENZAMIDE'>1NF</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xx9 OCA], [https://pdbe.org/2xx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xx9 RCSB], [https://www.ebi.ac.uk/pdbsum/2xx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xx9 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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
A novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and efficacy profiles, leading to identification of a clinical candidate. Unusually for an ion channel target, this optimization was integrated with regular generation of ligand-bound crystal structures and uncovered a novel chemotype with a unique and highly conserved mode of interaction via a trifluoromethyl group.
-
===CRYSTAL STRUCTURE OF 1-((2-FLUORO-4-(3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOL-1-YL)PHENYL)METHYL)-2-PYRROLIDINONE IN COMPLEX WITH THE LIGAND BINDING DOMAIN OF THE RAT GLUA2 RECEPTOR AND GLUTAMATE AT 2.2A RESOLUTION.===
+
Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of AMPA Receptor Positive Allosteric Modulators.,Ward SE, Harries M, Aldegheri L, Austin NE, Ballantine S, Ballini E, Bradley DM, Bax BD, Clarke BP, Harris AJ, Harrison SA, Melarange RA, Mookherjee C, Mosley J, Dal Negro G, Oliosi B, Smith KJ, Thewlis KM, Woollard PM, Yusaf SP J Med Chem. 2010 Dec 3. PMID:21128618<ref>PMID:21128618</ref>
-
{{ABSTRACT_PUBMED_21128618}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
==About this Structure==
+
<div class="pdbe-citations 2xx9" style="background-color:#fffaf0;"></div>
-
[[2xx9]] is a 3 chain structure with 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=2XX9 OCA].
+
==See Also==
==See Also==
-
*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
+
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:021128618</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
-
[[Category: Aldegheri, L.]]
+
[[Category: Aldegheri L]]
-
[[Category: Austin, N E.]]
+
[[Category: Austin NE]]
-
[[Category: Ballantine, S.]]
+
[[Category: Ballantine S]]
-
[[Category: Ballini, E.]]
+
[[Category: Ballini E]]
-
[[Category: Bax, B D.]]
+
[[Category: Bax BD]]
-
[[Category: Bradley, D M.]]
+
[[Category: Bradley DM]]
-
[[Category: Clarke, B P.]]
+
[[Category: Clarke BP]]
-
[[Category: Dalnegro, G.]]
+
[[Category: DalNegro G]]
-
[[Category: Harries, M.]]
+
[[Category: Harries M]]
-
[[Category: Harris, A J.]]
+
[[Category: Harris AJ]]
-
[[Category: Harrison, S A.]]
+
[[Category: Harrison SA]]
-
[[Category: Melarange, R A.]]
+
[[Category: Melarange RA]]
-
[[Category: Mookherjee, C.]]
+
[[Category: Mookherjee C]]
-
[[Category: Mosley, J.]]
+
[[Category: Mosley J]]
-
[[Category: Oliosi, B.]]
+
[[Category: Oliosi B]]
-
[[Category: Smith, K J.]]
+
[[Category: Smith KJ]]
-
[[Category: Thewlis, K M.]]
+
[[Category: Thewlis KM]]
-
[[Category: Ward, S E.]]
+
[[Category: Ward SE]]
-
[[Category: Woollard, P M.]]
+
[[Category: Woollard PM]]
-
[[Category: Yusaf, S P.]]
+
[[Category: Yusaf SP]]
-
[[Category: Ampa receptor ligand-binding core]]
+
-
[[Category: Ion channel]]
+
-
[[Category: Transport protein]]
+

Current revision

Crystal structure of 1-((2-fluoro-4-(3-(trifluoromethyl)-4,5,6,7- tetrahydro-1H-indazol-1-yl)phenyl)methyl)-2-pyrrolidinone in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 2.2A resolution.

PDB ID 2xx9

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/2xx9"
Personal tools