The Leu/Val^6.51 Side Chain of Cannabinoid Receptors Regulates the Binding Mode of the Alkyl Chain of Δ⁹-Tetrahydrocannabinol.

ABSTRACT: (-)-Δ⁹-trans-tetrahydrocannabinol (THC), which is the principal psychoactive constituent of Cannabis, mediates its action by binding to two members of the G-protein-coupled receptor (GPCR) family: the cannabinoid CB₁ (CB₁R) and CB₂ (CB₂R) receptors. Molecular dynamics simulations showed that the pentyl chain of THC could adopts an I-shape conformation, filling an intracellular cavity between Phe^3.36 and Trp^6.48 for initial agonist-induced receptor activation, in CB₁R but not in CB₂R. This cavity opens to the five-carbon chain of THC by the conformational change of the γ-branched, flexible, Leu^6.51 side chain of CB₁R, which is not feasible by the β-branched,

SUBMITTER: Llinas Del Torrent C 

PROVIDER: S-EPMC10523433 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature