This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3rnn

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:48, 25 December 2014

Crystal Structure of iGluR2 Ligand Binding Domain with Symmetric Sulfonamide Containing Potentiator

Structural highlights

3rnn is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3rn8, 1lbc, 1lb9, 1ftj, 1ftk, 1ftl
Gene:	GRIA2, GLUR2 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GRIA2_HUMAN] 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.^[1]

Publication Abstract from PubMed

At the dimer interface of the extracellular ligand-binding domain of AMPA receptors a hydrophilic pocket is formed that is known to interact with two classes of positive allosteric modulators, represented by cyclothiazide and the ampakine CX614. Here we present structural and functional data on two new positive allosteric modulators of AMPA receptors, CMPDA and CMPDB. Crystallographic data show that these compounds bind within the modulator-binding pocket, and that substituents of each compound overlap with distinct moieties of cyclothiazide and CX614. The goals of the present study were to determine 1) the degree of modulation by CMPDA and CMPDB of AMPA receptor deactivation and desensitization; 2) whether these compounds are splice isoform-selective; and, 3) whether predictions of mechanism of action could be inferred by comparing molecular interactions between the ligand binding domain and each compound to those of cyclothiazide and CX614. CMPDB was found to be more isoform-selective than would be predicted from initial binding assays. Importantly, these new compounds are both more potent and more efficacious, and also may be more clinically relevant, than the previously described AMPA receptor modulators.

Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation.,Timm DM, Benveniste M, Weeks AM, Nisenbaum ES, Partin KM Mol Pharmacol. 2011 May 4. PMID:21543522^[2]

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

References

↑ Ward SE, Harries M, Aldegheri L, Andreotti D, Ballantine S, Bax BD, Harris AJ, Harker AJ, Lund J, Melarange R, Mingardi A, Mookherjee C, Mosley J, Neve M, Oliosi B, Profeta R, Smith KJ, Smith PW, Spada S, Thewlis KM, Yusaf SP. Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfo namide, a Novel Clinical AMPA Receptor Positive Modulator. J Med Chem. 2010 Jul 8. PMID:20614889 doi:10.1021/jm1005429
↑ Timm DM, Benveniste M, Weeks AM, Nisenbaum ES, Partin KM. Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation. Mol Pharmacol. 2011 May 4. PMID:21543522 doi:10.1124/mol.110.070243

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/3rnn"

Categories: Homo sapiens | Timm, D E | Iglur2 ligand binding domain | Membrane | Transport protein

@@ Line 8: / Line 8: @@
 <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=3rnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rnn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rnn RCSB], [http://www.ebi.ac.uk/pdbsum/3rnn PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN]] 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:20614889</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3rnn

From Proteopedia

Revision as of 09:48, 25 December 2014

Crystal Structure of iGluR2 Ligand Binding Domain with Symmetric Sulfonamide Containing Potentiator

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox