1rgr: Difference between revisions

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[[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1rgr" />

'''Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA].

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==

Line 15:

[[Category: Li, T.]]

[[Category: Marshall, J.]]

[[Category: Mierke, D.F.]]

[[Category: Mierke, D F.]]

[[Category: Piserchio, A.]]

[[Category: Salinas, G.D.]]

[[Category: Salinas, G D.]]

[[Category: Spaller, M.R.]]

[[Category: Spaller, M R.]]

[[Category: BAL]]

[[Category: pdz1 domain]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 01:35:~~09 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:44 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1rgr.gif|left|200px]]<br /><applet load="1rgr" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1rgr" />
 '''Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability'''<br />
 ==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.
+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==
-RGR 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RGR OCA].
+RGR 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==
@@ Line 15: / Line 15: @@
 [[Category: Li, T.]]
 [[Category: Marshall, J.]]
-[[Category: Mierke, D.F.]]
+[[Category: Mierke, D F.]]
 [[Category: Piserchio, A.]]
-[[Category: Salinas, G.D.]]
+[[Category: Salinas, G D.]]
-[[Category: Spaller, M.R.]]
+[[Category: Spaller, M R.]]
 [[Category: BAL]]
 [[Category: pdz1 domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:35:09 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:44 2008''