1rgr
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(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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Revision as of 23:27, 20 November 2007
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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 BAL 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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