1RGR
Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability
Summary for 1RGR
| Entry DOI | 10.2210/pdb1rgr/pdb |
| Descriptor | Presynaptic density protein 95, postsynaptic protein CRIPT peptide, BETA-ALANINE (3 entities in total) |
| Functional Keywords | pdz1 domain, structural protein-de novo protein complex, structural protein/de novo protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Cellular location | Cell membrane; Peripheral membrane protein: P31016 |
| Total number of polymer chains | 2 |
| Total formula weight | 11718.13 |
| Authors | Piserchio, A.,Salinas, G.D.,Li, T.,Marshall, J.,Spaller, M.R.,Mierke, D.F. (deposition date: 2003-11-12, release date: 2004-05-18, Last modification date: 2024-10-30) |
| Primary citation | Piserchio, A.,Salinas, G.D.,Li, T.,Marshall, J.,Spaller, M.R.,Mierke, D.F. Targeting Specific PDZ Domains of PSD-95; Structural Basis for Enhanced Affinity and Enzymatic Stability of a Cyclic Peptide. Chem.Biol., 11:469-473, 2004 Cited by PubMed Abstract: 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. PubMed: 15123241DOI: 10.1016/j.chembiol.2004.03.013 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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