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 Buffalo rat. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BAL Gene: DLG4, PSD95 (Buffalo rat) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [DLG4_RAT] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. 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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