1rgr

From Proteopedia

(Difference between revisions)

Current revision

Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability

Structural highlights

1rgr is a 2 chain structure with sequence from Rattus norvegicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 22 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DLG4_RAT Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(betaAla)-]-Val, incorporating a beta-Ala lactam side chain linker and designed to target the PDZ domains of the postsynaptic density protein 95 (PSD-95), has been synthesized and structurally characterized by NMR while free and bound to the PDZ1 domain of PSD-95. While bound, the lactam linker of the peptide makes a number of unique contacts outside the canonical PDZ binding motif, providing a novel target for PDZ-domain specificity as well as producing a 10-fold enhancement in binding affinity. Additionally, the cyclization greatly enhances the enzymatic stability, increasing the duration that the peptide inhibits the association between PSD-95 and glutamate receptors, effectively inhibiting the clustering of kainate receptors for over 14 hr after application. Highly specific regulation of kainate receptor action may provide a novel route for treatment of drug addiction and epilepsy.

Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide.,Piserchio A, Salinas GD, Li T, Marshall J, Spaller MR, Mierke DF Chem Biol. 2004 Apr;11(4):469-73. PMID:15123241^[3]

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

References

↑ Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200
↑ Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101
↑ Piserchio A, Salinas GD, Li T, Marshall J, Spaller MR, Mierke DF. Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide. Chem Biol. 2004 Apr;11(4):469-73. PMID:15123241 doi:10.1016/j.chembiol.2004.03.013

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1rgr"

@@ Line 1: / Line 1: @@
 ==Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability==
-<StructureSection load='1rgr' size='340' side='right'caption='[[1rgr]], [[NMR_Ensembles_of_Models | 22 NMR models]]' scene=''>
+<StructureSection load='1rgr' size='340' side='right'caption='[[1rgr]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1rgr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RGR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1rgr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RGR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAL:BETA-ALANINE'>BAL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 22 models</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLG4, PSD95 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAL:BETA-ALANINE'>BAL</scene></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=1rgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgr OCA], [https://pdbe.org/1rgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rgr RCSB], [https://www.ebi.ac.uk/pdbsum/1rgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rgr ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DLG4_RAT DLG4_RAT]] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.<ref>PMID:15317815</ref> <ref>PMID:15358863</ref>
+[https://www.uniprot.org/uniprot/DLG4_RAT DLG4_RAT] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.<ref>PMID:15317815</ref> <ref>PMID:15358863</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rg/1rgr_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 1rgr" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Postsynaptic density protein 3D structures|Postsynaptic density protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Li, T]]
+[[Category: Rattus norvegicus]]
-[[Category: Marshall, J]]
+[[Category: Li T]]
-[[Category: Mierke, D F]]
+[[Category: Marshall J]]
-[[Category: Piserchio, A]]
+[[Category: Mierke DF]]
-[[Category: Salinas, G D]]
+[[Category: Piserchio A]]
-[[Category: Spaller, M R]]
+[[Category: Salinas GD]]
-[[Category: Pdz1 domain]]
+[[Category: Spaller MR]]
-[[Category: Structural protein-de novo protein complex]]

1rgr

From Proteopedia

Current revision

Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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