4ymb

From Proteopedia

(Difference between revisions)

Revision as of 12:12, 7 October 2017

Structure of the ligand-binding domain of GluK1 in complex with the antagonist CNG10111

Structural highlights

4ymb is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4e0x
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRIK1_RAT] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.^[1]

Publication Abstract from PubMed

Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 muM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 A resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8 degrees and 2f a domain opening in GluK1-LBD of 17.0-17.5 degrees relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.,Krogsgaard-Larsen N, Storgaard M, Moller C, Demmer CS, Hansen J, Han L, Monrad RN, Nielsen B, Tapken D, Pickering DS, Kastrup JS, Frydenvang K, Bunch L J Med Chem. 2015 Jul 22. PMID:26200741^[2]

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

References

↑ Mayer ML, Ghosal A, Dolman NP, Jane DE. Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. J Neurosci. 2006 Mar 15;26(11):2852-61. PMID:16540562 doi:26/11/2852
↑ Krogsgaard-Larsen N, Storgaard M, Moller C, Demmer CS, Hansen J, Han L, Monrad RN, Nielsen B, Tapken D, Pickering DS, Kastrup JS, Frydenvang K, Bunch L. Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid. J Med Chem. 2015 Jul 22. PMID:26200741 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00750

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/4ymb"

@@ Line 1: / Line 1: @@
 ==Structure of the ligand-binding domain of GluK1 in complex with the antagonist CNG10111==
 <StructureSection load='4ymb' size='340' side='right' caption='[[4ymb]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4E7:(3R,4S)-3-(3-CARBOXYPHENYL)-4-PROPYL-L-PROLINE'>4E7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e0x|4e0x]]</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=4ymb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ymb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ymb RCSB], [http://www.ebi.ac.uk/pdbsum/4ymb PDBsum]</span></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=4ymb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ymb OCA], [http://pdbe.org/4ymb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ymb RCSB], [http://www.ebi.ac.uk/pdbsum/4ymb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ymb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ymb" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
 == References ==
 <references/>

4ymb

From Proteopedia

Revision as of 12:12, 7 October 2017

Structure of the ligand-binding domain of GluK1 in complex with the antagonist CNG10111

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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