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- W78885703 abstract "The cannabinoid receptors belong to Class A of the G protein-coupled receptor (GPCR) family. GPCRs are assumed to have a common topology and to share a common molecular activation mechanism involving their intracellular domains. However, each individual receptor will also have a molecular switch within the ligand-binding pocket that is a noncovalent, intramolecular interaction in the basal state of the GPCR that must be disrupted to achieve an active state. Knowledge of the molecular switch within the ligand-binding pocket can greatly facilitate the rational design of inverse agonists, neutral antagonists, and agonists.This chapter reviews the experimental literature on GPCR structure and activation and then focuses on sequence divergences between the cannabinoid CB1/CB2 receptors and other Class A GPCRs that may cause CB1 and CB2 to diverge from the structure of the prototypical Class A GPCR, rhodospin. Results of computer modeling, mutation, and covalent labeling studies are presented that have led to our current understanding of cannabinoid CB1 and CB2 receptor structure and activation at a molecular level. An outgrowth of these studies has been the identification of the CB1 receptor F3.36/W6.48 molecular toggle switch. The design of compounds that stabilizes this toggle switch (inverse agonists) versus those that disrupt the switch (agonists) are presented by examining the interaction of each cannabinoid ligand structural class at their receptors." @default.
- W78885703 created "2016-06-24" @default.
- W78885703 creator A5068361479 @default.
- W78885703 creator A5089461409 @default.
- W78885703 date "2009-01-01" @default.
- W78885703 modified "2023-09-27" @default.
- W78885703 title "Models of Cannabinoid Inverse Agonism, Neutral Antagonism, and Agonism: Tools for Rational Drug Design" @default.
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