PMID: 9547370May 9, 1998Paper

Creating a functional opioid alkaloid binding site in the orphanin FQ receptor through site-directed mutagenesis

Molecular Pharmacology
F MengH Akil

Abstract

Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding of opioid versus nonopioid ligands. In the current study, we adopt a "gain of function" approach aimed at shifting the binding profile of the orphanin FQ receptor toward that of the opioid receptors. After two rounds of mutagenesis, several orphanin FQ receptor mutants can be labeled with the opiate alkaloid [3H]naltrindole and show greatly increased affinities toward the opiate antagonists naltrexone, nor-binaltrophine HCl, and (-)-bremazocine. These orphanin FQ receptor mutants also display stereospecificity similar to that of opioid receptors. Furthermore, the orphanin FQ receptor mutant that has the best affinities toward the opioid alkaloids shows, in the presence of GTP and high salt concentration, an affinity-shift profile similar to that of the delta receptor. Most strikingly, the same mutant exhibits naltrindole-sensitive etorphine-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate binding, whereas the ef...Continue Reading

References

Apr 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·A J Blume
Oct 1, 1992·European Journal of Pharmacology·A MansourH Akil
Jan 1, 1992·Analytical Biochemistry·W P Deng, J A Nickoloff
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Jun 1, 1995·Trends in Pharmacological Sciences·T Kenakin
Aug 1, 1994·Current Opinion in Biotechnology·T W Schwartz
Jan 1, 1995·Journal of Neurochemistry·J E LachowiczD R Sibley
Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·W W WangR D Howells
Jun 14, 1996·The Journal of Biological Chemistry·R K ReinscheidO Civelli
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·H P NothackerO Civelli
Apr 4, 1996·European Journal of Pharmacology·X LiH I Yamamura
Dec 13, 1996·The Journal of Biological Chemistry·F MengH Akil

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Citations

Mar 30, 2001·Journal of Peptide Science : an Official Publication of the European Peptide Society·B P Roques
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Constance E Owens, Huda Akil
Jul 9, 2003·Nature Structural Biology·Fabien M DécaillotBrigitte L Kieffer
Jan 18, 2018·Journal of Computer-aided Molecular Design·Stefano Della Longa, Alessandro Arcovito
May 27, 2004·Proteins·Paul R GouldsonChristopher A Reynolds
May 19, 2012·Nature·Sébastien GranierBrian K Kobilka
Dec 16, 2005·The AAPS Journal·Irina D PogozhevaHenry I Mosberg
Mar 11, 2000·Neuroscience Research·C H BrownG Leng
Aug 26, 2014·Journal of Chemical Information and Modeling·Pankaj R DagaNurulain T Zaveri

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