Cysteine 2.59(89) in the Second Transmembrane Domain of Human CB2 Receptor Is Accessible within the Ligand Binding Crevice: Evidence for Possible CB2 Deviation from a Rhodopsin Template

@article{Zhang2005Cysteine2I,
  title={Cysteine 2.59(89) in the Second Transmembrane Domain of Human CB2 Receptor Is Accessible within the Ligand Binding Crevice: Evidence for Possible CB2 Deviation from a Rhodopsin Template},
  author={Rundong Zhang and Dow P. Hurst and Judy Barnett-Norris and Patricia H. Reggio and Zhao-hui Song},
  journal={Molecular Pharmacology},
  year={2005},
  volume={68},
  pages={69 - 83}
}
In this study, the sensitivity of the CB2 receptor to methanethiosulfonate (MTS) derivatives was tested, and a native cysteine residue conferring the sensitivity was identified. By incubating human embryonic kidney 293 cells stably transfected with CB2 receptors and MTS derivatives such as MTS ethylammonium (MTSEA), [3H]HU-243 binding was inhibited. Pretreatment of the CB2 receptor with cannabinoid ligands prevented this inhibition, suggesting that MTSEA modification occurred within the binding… 
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43 Citations

Mutation Studies of Ser7.39 and Ser2.60 in the Human CB1 Cannabinoid Receptor: Evidence for a Serine-Induced Bend in CB1 Transmembrane Helix 7
TLDR
Results clearly suggest that Ser7.39, but not Ser2.60, plays a crucial role in mediating ligand specific interactions for CP55,940, HU210, and AM4056 at the human CB1 receptor.
Mutagenesis and computer modeling studies of a GPCR conserved residue W5.43(194) in ligand recognition and signal transduction for CB2 receptor.
Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor
TLDR
Ligand docking to the CXCR4-based model of the P2Y12R predicted poses of both reversibly and irreversibly-binding small molecules, consistent with observed pharmacology and mutagenesis studies.
hCB2 ligand-interaction landscape: cysteine residues critical to biarylpyrazole antagonist binding motif and receptor modulation.
CB2-Selective Cannabinoid Receptor Ligands: Synthesis, Pharmacological Evaluation, and Molecular Modeling Investigation of 1,8-Naphthyridin-2(1H)-one-3-carboxamides
TLDR
A number of additional derivatives in which the same central scaffold has been variously functionalized in position 1 or 6 of the naphthyridine scaffold, showing high selectivity and affinity in the nanomolar range for the CB2 receptor.
Methods for the Development of In Silico GPCR Models.
Endogenous lipid activated G protein-coupled receptors: emerging structural features from crystallography and molecular dynamics simulations.
6-Methoxy-N-alkyl isatin acylhydrazone derivatives as a novel series of potent selective cannabinoid receptor 2 inverse agonists: design, synthesis, and binding mode prediction.
TLDR
A ligand-based homology model of the CB2 binding site was developed, and on the basis of the results, a general binding mode for this class of inverse agonists with CB2 is proposed.
Global fold of human cannabinoid type 2 receptor probed by solid‐state 13C‐, 15N‐MAS NMR and molecular dynamics simulations
TLDR
The experimental NMR spectra matched the calculated spectra reasonably well indicating agreement of the global fold of the protein between experiment and simulations, and the 13C chemical shift distribution of Cα resonances was shown to be very sensitive to both the primary amino acid sequence and the secondary structure of CB2.
A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor*
TLDR
To the authors' knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstrated via molecular dynamics of Gprotein-cOUpled receptor activation triggered by aligand binding event.
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References

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