View source for 4nwc

==Crystal structure of the GluK3 ligand-binding domain (S1S2) in complex with the agonist (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic acid at 2.01 A resolution.==
<StructureSection load='4nwc' size='340' side='right' caption='[[4nwc]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nwc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NWC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QE:(2S,4R)-4-(3-METHOXY-3-OXOPROPYL)+GLUTAMIC+ACID'>2QE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3s9e|3s9e]], [[4mh5|4mh5]]</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=4nwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nwc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nwc RCSB], [http://www.ebi.ac.uk/pdbsum/4nwc PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The kainate receptors are the least studied subfamily of ionotropic glutamate receptors. These receptors are thought to have a neuromodulatory role and have been associated with a variety of disorders in the central nervous system. This makes kainate receptors interesting potential drug targets. Today, structures of the ligand binding domain (LBD) of the kainate receptor GluK3 are only known in complex with the endogenous agonist glutamate, the natural product kainate, and two synthetic agonists. Herein we report structures of GluK3 LBD in complex with two 2,4-syn-functionalized (S)-glutamate analogues to investigate their structural potential as chemical scaffolds. Similar binding affinities at GluK3 were determined for the 2-(methylcarbamoyl)ethyl analogue (Ki =4.0 muM) and the 2-(methoxycarbonyl)ethyl analogue (Ki =1.7 muM), in agreement with the similar positioning of the compounds within the binding pocket. As the binding affinity is similar to that of glutamate, this type of Cgamma substituent could be used as a scaffold for introduction of even larger substituents reaching into unexplored binding site regions to achieve subtype selectivity.

Molecular Recognition of Two 2,4-syn-Functionalized (S)-Glutamate Analogues by the Kainate Receptor GluK3 Ligand Binding Domain.,Venskutonyte R, Larsen AP, Frydenvang K, Gajhede M, Sagot E, Assaf Z, Gefflaut T, Pickering DS, Bunch L, Kastrup JS ChemMedChem. 2014 Jul 8. doi: 10.1002/cmdc.201402204. PMID:25044437<ref>PMID:25044437</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Frydenvang, K.]]
[[Category: Gajhede, M.]]
[[Category: Kastrup, J S.]]
[[Category: Larsen, A P.]]
[[Category: Venskutonyte, R.]]
[[Category: Agonist]]
[[Category: Ionotropic glutamate receptor]]
[[Category: Kainate receptor ligand-binding domain]]
[[Category: Membrane protein]]
[[Category: Receptor-agonist complex]]