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3tza

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{{STRUCTURE_3tza| PDB=3tza | SCENE= }}
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==Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with the antagonist (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid at 1.9A resolution==
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===Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with the antagonist (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid at 1.9A resolution===
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<StructureSection load='3tza' size='340' side='right' caption='[[3tza]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21923187}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3tza]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TZA FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TZG:(S)-2-AMINO-3-(2-(2-CARBOXYETHYL)-5-CHLORO-4-NITROPHENYL)PROPIONIC+ACID'>TZG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n0t|1n0t]], [[1ftl|1ftl]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gria2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=32630 synthetic construct])</td></tr>
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<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=3tza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tza OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tza RCSB], [http://www.ebi.ac.uk/pdbsum/3tza PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In order to map out molecular determinants for competitive blockade of AMPA receptor subtypes, a series of 2-carboxyethylphenylalanine derivatives has been synthesized and pharmacologically characterized in vitro. One compound in this series, (RS)-3h, showed micromolar affinity for GluA1(o) and GluA2(R)(o) receptors with an approximately 4-fold preference for GluA1/2 vs GluA3/4. In TEVC electrophysiological experiments (RS)-3h competitively antagonized GluA2(Q)(i) receptors. The X-ray structure of the active enantiomer (S)-3h in complex with GluA2-S1S2J showed a domain closure around 8 degrees . Even though the nitro and the carboxyethyl groups of (S)-3h were both anchored to Tyr702 through a water H-bond network, these interactions only induced weak subtype selectivity. In spite of the fact that (S)-3h induced a domain closure close to that observed for partial agonists, it did not produce agonist responses at GluA2 receptors under nondesensitizing conditions. 2-Carboxyethylphenylalanine derivatives provide a new synthetic scaffold for the introduction of substituents that could lead to AMPA receptor subtype-selective ligands.
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==Function==
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A New Phenylalanine Derivative Acts as an Antagonist at the AMPA Receptor GluA2 and Introduces Partial Domain Closure: Synthesis, Resolution, Pharmacology, and Crystal Structure.,Szymanska E, Frydenvang K, Contreras-Sanz A, Pickering DS, Frola E, Serafimoska Z, Nielsen B, Kastrup JS, Johansen TN J Med Chem. 2011 Oct 27;54(20):7289-98. Epub 2011 Oct 4. PMID:21923187<ref>PMID:21923187</ref>
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[[http://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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3tza]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZA OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:021923187</ref><references group="xtra"/><references/>
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*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Synthetic construct]]
[[Category: Synthetic construct]]
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[[Category: Frydenvang, K.]]
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[[Category: Frydenvang, K]]
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[[Category: Kastrup, J S.]]
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[[Category: Kastrup, J S]]
[[Category: Ampa receptor ligand-binding domain]]
[[Category: Ampa receptor ligand-binding domain]]
[[Category: Antagonist]]
[[Category: Antagonist]]
[[Category: Glua2-s1s2j]]
[[Category: Glua2-s1s2j]]
[[Category: Membrane protein]]
[[Category: Membrane protein]]

Revision as of 07:37, 21 December 2014

Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with the antagonist (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid at 1.9A resolution

3tza, resolution 1.90Å

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