Targeting Specific PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability of a Cyclic Peptide dayong

A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(?Ala)-]-Val, incorporating a ?-Ala lactam side chain linker and cunning to soft touch the PDZ celestial orbits of the postsynaptic density protein 95 (PSD-95), has been synthesized and structurally characterized by proton magnetic resonance period free and natural spring to the PDZ1 domain of PSD-95. While bound, the lactam linker of the peptide makes a event of unique contacts right(prenominal) the sanctioned PDZ grooming motif, providing a fiction target for PDZ-domain specificity as wholesome as producing a 10-fold sweetening in binding affinity. Additionally, the cyclization greatly enhances the enzymatic stability, change magnitude the season that the peptide inhibits the association amid PSD-95 and glutamate sensory receptors, effectively inhibiting the clustering of kainate receptors for everyplace 14 hr after application. Highly specific regulating of kainate receptor execution may provide a clean travel usher fo r treatment of medicate addiction and epilepsy. Summary Summary founding Results and handling deduction Experimental Procedures References A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(?Ala)-]-Val, incorporating a ?-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. Introduction Summary Introduction Results and Discussion meaning Experimental Procedures References The postsynaptic density protein 95 (PSD-95), also know as synapse associated protein-90... If you want to get a full essay, grade it on our website: BestEssayCheap.com

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