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1rgr

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[[Image:1rgr.gif|left|200px]]
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{{STRUCTURE_1rgr| PDB=1rgr | SCENE= }}
{{STRUCTURE_1rgr| PDB=1rgr | SCENE= }}
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'''Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability'''
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===Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15123241}}
==About this Structure==
==About this Structure==
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1RGR is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA].
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1RGR is a [[Protein complex]] structure of sequences from [http://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].
==Reference==
==Reference==
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[[Category: Spaller, M R.]]
[[Category: Spaller, M R.]]
[[Category: Pdz1 domain]]
[[Category: Pdz1 domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:28:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:21:43 2008''

Revision as of 17:21, 28 July 2008

Image:1rgr.png

Template:STRUCTURE 1rgr

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

Template:ABSTRACT PUBMED 15123241

About this Structure

1RGR is a Protein complex structure of sequences from Rattus norvegicus. Full experimental information is available from OCA.

Reference

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

Page seeded by OCA on Mon Jul 28 20:21:43 2008

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