1rgr
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= DLG4, PSD95 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |GENE= DLG4, PSD95 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgr OCA], [http://www.ebi.ac.uk/pdbsum/1rgr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rgr RCSB]</span> | ||
}} | }} | ||
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[[Category: Salinas, G D.]] | [[Category: Salinas, G D.]] | ||
[[Category: Spaller, M R.]] | [[Category: Spaller, M R.]] | ||
| - | [[Category: BAL]] | ||
[[Category: pdz1 domain]] | [[Category: pdz1 domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:27:57 2008'' |
Revision as of 20:28, 30 March 2008
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| Ligands: | |||||||
| Gene: | DLG4, PSD95 (Rattus norvegicus) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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