1rgr | pdb_00001rgr

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

spinqualitylabelsall models 1rgr, 22 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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. Ligands: BAL Gene: DLG4, PSD95 (Rattus norvegicus) Resources: FirstGlance, OCA, RCSB, PDBsum 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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