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4nwc

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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.

Structural highlights

4nwc is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.012Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRIK3_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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.^[1]

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^[2]

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

References

↑ Venskutonyte R, Frydenvang K, Gajhede M, Bunch L, Pickering DS, Kastrup JS. Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate. J Struct Biol. 2011 Sep 1. PMID:21907808 doi:10.1016/j.jsb.2011.08.014
↑ Venskutonyte R, Larsen AP, Frydenvang K, Gajhede M, Sagot E, Assaf Z, Gefflaut T, Pickering DS, Bunch L, Kastrup JS. Molecular Recognition of Two 2,4-syn-Functionalized (S)-Glutamate Analogues by the Kainate Receptor GluK3 Ligand Binding Domain. ChemMedChem. 2014 Jul 8. doi: 10.1002/cmdc.201402204. PMID:25044437 doi:http://dx.doi.org/10.1002/cmdc.201402204

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/4nwc"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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>
+<table><tr><td colspan='2'>[[4nwc]] is a 1 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=4NWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.012&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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://pdbe.org/4nwc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nwc RCSB], [http://www.ebi.ac.uk/pdbsum/4nwc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nwc ProSAT]</span></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=4nwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nwc OCA], [https://pdbe.org/4nwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nwc RCSB], [https://www.ebi.ac.uk/pdbsum/4nwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nwc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRIK3_RAT GRIK3_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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.<ref>PMID:21907808</ref>
+[https://www.uniprot.org/uniprot/GRIK3_RAT GRIK3_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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.<ref>PMID:21907808</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Frydenvang, K]]
+[[Category: Large Structures]]
-[[Category: Gajhede, M]]
+[[Category: Rattus norvegicus]]
-[[Category: Kastrup, J S]]
+[[Category: Frydenvang K]]
-[[Category: Larsen, A P]]
+[[Category: Gajhede M]]
-[[Category: Venskutonyte, R]]
+[[Category: Kastrup JS]]
-[[Category: Agonist]]
+[[Category: Larsen AP]]
-[[Category: Ionotropic glutamate receptor]]
+[[Category: Venskutonyte R]]
-[[Category: Kainate receptor ligand-binding domain]]
-[[Category: Membrane protein]]
-[[Category: Receptor-agonist complex]]

4nwc

From Proteopedia

Current revision

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.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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