ArticleBiochemistry2008
Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Methods for the Development of In Silico GPCR Models.Methods in enzymology · 2017Article
- Chromenopyrazole, a Versatile Cannabinoid Scaffold with in Vivo Activity in a Model of Multiple Sclerosis.Journal of medicinal chemistry · 2016Article
- Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.Journal of chemical information and modeling · 2016Article
- Minireview: From the bench, toward the clinic: therapeutic opportunities for cannabinoid receptor modulation.Molecular endocrinology (Baltimore, Md.) · 2015Review
- CB2-selective cannabinoid receptor ligands: synthesis, pharmacological evaluation, and molecular modeling investigation of 1,8-Naphthyridin-2(1H)-one-3-carboxamides.Journal of medicinal chemistry · 2014Article
- Examining the critical roles of human CB2 receptor residues Valine 3.32 (113) and Leucine 5.41 (192) in ligand recognition and downstream signaling activities.Biochemical and biophysical research communications · 2014Article
- Modeling, molecular dynamics simulation, and mutation validation for structure of cannabinoid receptor 2 based on known crystal structures of GPCRs.Journal of chemical information and modeling · 2014Article
- Global fold of human cannabinoid type 2 receptor probed by solid-state 13C-, 15N-MAS NMR and molecular dynamics simulations.Proteins · 2014Article
- The importance of hydrogen bonding and aromatic stacking to the affinity and efficacy of cannabinoid receptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528).Journal of medicinal chemistry · 2013Article
- Chromenopyrazoles: non-psychoactive and selective CB₁ cannabinoid agonists with peripheral antinociceptive properties.ChemMedChem · 2012Article
- Recombinant cannabinoid type 2 receptor in liposome model activates g protein in response to anionic lipid constituents.The Journal of biological chemistry · 2012Article
- Mutagenesis and computer modeling studies of a GPCR conserved residue W5.43(194) in ligand recognition and signal transduction for CB2 receptor.International immunopharmacology · 2011Article
- Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands.Biochemistry · 2011Article
- Article
- A lipid pathway for ligand binding is necessary for a cannabinoid G protein-coupled receptor.The Journal of biological chemistry · 2010Article
- Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown.Current medicinal chemistry · 2010Review
- Understanding functional residues of the cannabinoid CB1.Current topics in medicinal chemistry · 2010Review
- Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments.Biochemical and biophysical research communications · 2009Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We have used the substituted-cysteine accessibility method (SCAM) to map the residues in the sixth membrane-spanning segment of the CB2 cannabinoid receptor that contribute to the surface of the water-accessible binding-site crevice. Using a background of the mutant C2.59S which is relatively insensitive to the methanethiosulfonate (MTS) reagents, we mutated to cysteine, one at a time, 34 consecutive residues in TMH6 of the CB2 receptor. These mutant receptors were then expressed in HEK293 cells. By incubating HEK293 cells stably transfected with CB2 receptors with the small, charged, hydrophilic, thiol-specific reagent methanethiosulfonate ethylammonium (MTSEA), [(3)H]CP55940 binding was significantly inhibited for six mutant receptors. All six of the mutants that reacted with MTSEA were protected from the reaction when pretreated with the cannabinoid agonist WIN55212-2, suggesting that MTSEA modification occurred within the binding crevice. Therefore, the side chains of the residues at these reactive loci (V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62) are on the water-accessible surface of the binding-site crevice. These residues are extracellular to the TMH6 CWXP hinge motif. The pattern of accessibility is consistent with a alpha-helical conformation for this segment of TMH6. Molecular modeling studies performed in the context of the CB2 model show that V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62 face into the CB2 binding pocket, further confirming our SCAM results. These results are similar to the accessibility patterns determined by SCAM studies of TMH6 in the opioid and dopamine D2 receptors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.