1rgr
From Proteopedia
(New page: 200px<br /><applet load="1rgr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rgr" /> '''Cyclic Peptides Targeting PDZ Domains of PSD...) |
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| - | [[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size=" | + | [[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability'''<br /> | '''Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(betaAla)-]-Val, incorporating a | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1RGR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with BAL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1RGR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=BAL:'>BAL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Li, T.]] | [[Category: Li, T.]] | ||
[[Category: Marshall, J.]] | [[Category: Marshall, J.]] | ||
| - | [[Category: Mierke, D | + | [[Category: Mierke, D F.]] |
[[Category: Piserchio, A.]] | [[Category: Piserchio, A.]] | ||
| - | [[Category: Salinas, G | + | [[Category: Salinas, G D.]] |
| - | [[Category: Spaller, M | + | [[Category: Spaller, M R.]] |
[[Category: BAL]] | [[Category: BAL]] | ||
[[Category: pdz1 domain]] | [[Category: pdz1 domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:44 2008'' |
Revision as of 12:50, 21 February 2008
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Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability
Overview
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.
About this Structure
1RGR is a Protein complex structure of sequences from Rattus norvegicus with as ligand. Full crystallographic 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
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