PMID: 9422382Jan 9, 1998Paper

Mutagenesis of a single amino acid in the rat mu-opioid receptor discriminates ligand binding

Journal of Neurochemistry
G BotT Reisine

Abstract

To investigate the role of Asp114 in the cloned rat mu-opioid receptor for ligand binding, the charged amino acid was mutated to an asparagine to generate the mutant mu receptor D114N. The wild-type mu receptor and the D114N mutant were then stably expressed in human embryonic kidney 293 cells, and the binding affinities of a series of opioids were investigated. The mu-selective agonists [D-Ala2,MePhe4,Gly-ol5]enkephalin and morphine and the endogenous peptides Met-enkephalin and beta-endorphin exhibited greatly reduced affinities for the D114N mutant compared with the wild-type mu receptor, as did the potent synthetic agonist etorphine. In contrast to the full agonists, the partial agonists buprenorphine and nalorphine and the antagonists diprenorphine and naloxone bound with similar affinities to the wild-type and D114N mutant mu receptors. The reduced affinities of the full agonists for the D114N mutant did not involve an uncoupling of the receptor from G proteins because methadone and etorphine stimulated the D114N mu receptors to inhibit adenylyl cyclase. Although the Asp114 to Asn114 mutation reduced full-agonist binding, mutation of His297 to Asn297 in the mu receptor did not but, in contrast, did reduce binding affinity...Continue Reading

Citations

Dec 16, 2005·The AAPS Journal·Irina D PogozhevaHenry I Mosberg
Feb 15, 2001·Biopolymers·K ChaturvediR D Howells
Mar 26, 2005·Protein Engineering, Design & Selection : PEDS·David OttAndreas Plückthun
Sep 11, 2004·European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine·Joeri SterkenChristian Verborgh
Jul 9, 2003·Journal of Peptide Science : an Official Publication of the European Peptide Society·Kálmán Medzihradszky
Mar 17, 2000·Brain Research. Molecular Brain Research·K ChaturvediR D Howells
Sep 24, 1999·European Journal of Pharmacology·K O LeeJ R Traynor
Dec 27, 2005·Bioorganic & Medicinal Chemistry·Ljiljana Dosen-MicovicVuk Micovic
Jun 6, 2006·Cellular Signalling·Nicolas MarieStéphane Allouche
Jul 8, 2015·ACS Chemical Neuroscience·András VáradiSusruta Majumdar

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