PMID: 8947918Nov 1, 1996Paper

Application of the message-address concept to the docking of naltrexone and selective naltrexone-derived opioid antagonists into opioid receptor models

Neurochemical Research
T G MetzgerD M Ferguson

Abstract

A binding site model for the opioid family of G-protein coupled receptors (GPCRs) is proposed based on the message-address concept of ligand recognition. Using ligand docking studies of the universal opioid antagonist, naltrexone, the structural basis for "message' recognition is explored across all three receptor types, mu, delta, and kappa. The binding mode proposed and basis for selectivity are also rationalized using the naltrexone-derived ligands, naltrindole (NTI) and norbinaltorphimine (nor BNI). These ligands are docked to the receptor according to the common naltrexone core or message. The resulting orientation places key "address' elements in close proximity to amino acid residues critical to selectivity among receptors types. Selectivity is explained by sequence differences in the mu, delta, and kappa receptors at these recognition points. Support for the model is derived from site directed mutagenesis studies and ligand binding data for the opioid receptors and other related GPCRs.

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Citations

May 15, 2008·Chemical Reviews·Thomas E Prisinzano, Richard B Rothman
Mar 23, 2012·Nature·Huixian WuRaymond C Stevens
Mar 30, 2011·Pharmacological Reviews·Christopher W CunninghamThomas E Prisinzano
Apr 6, 2006·The AAPS Journal·Brian E KaneDavid M Ferguson
May 1, 2009·Future Medicinal Chemistry·Kimberly M LovellThomas E Prisinzano
May 29, 2009·British Journal of Anaesthesia·N DietisD G Lambert
Dec 29, 2009·Journal of Molecular Graphics & Modelling·Attila Borics, Géza Tóth
May 6, 2008·Journal of Molecular Graphics & Modelling·Nidhi SinghChristopher R McCurdy
Jul 6, 2004·European Journal of Biochemistry·Ke-He RuanCheng-Huai Ruan
Apr 28, 2006·The FEBS Journal·Brian E KaneDavid M Ferguson
Jan 5, 2002·Biopolymers·G R Marshall
May 22, 2010·ChemMedChem·Attila KeresztesGéza Tóth
Aug 19, 2007·Physiology·Andrei R ManolescuChris Cheeseman
Apr 25, 2002·Journal of the American Chemical Society·Yirong MoDavid M Ferguson
Jul 14, 2000·Journal of Medicinal Chemistry·W C StevensP S Portoghese
Feb 12, 2000·Journal of Medicinal Chemistry·G SubramanianD M Ferguson
Apr 4, 2003·Journal of Medicinal Chemistry·Ulrike Holzgrabe, Wolfgang Brandt
May 21, 2021·Journal of Molecular Graphics & Modelling·Amr H SalehMohamed A Helal
Sep 15, 2005·Chemical Reviews·Francesca Fanelli, Pier G De Benedetti
Oct 18, 2002·Journal of Medicinal Chemistry·Manuela IadanzaHans-Dieter Höltje
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Mar 6, 2003·Journal of the American Chemical Society·Denzil BernardAlexander D MacKerell
Aug 6, 2004·Journal of Medicinal Chemistry·Luciana MarinelliHorst Kessler

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