The cannabinoid type 2 receptor (CB2R) is a target for the treatment of neurophatic pain and several other disorders. Solving the 3-dimensional structure of CB2R would enable the design of better CB2R-selective drugs. Although 30-50% of all current therapeutic drugs on the market modulate the action of different G protein coupled receptors (GPCRs), rhodopsin is the only GPCR for which the crystal structure is known. The bottleneck for GPCR crystallization has been the difficulty to generate large quantities of high-quality receptor sample needed for crystallography.
The aim of this project is the crystallization and structural elucidation of CB2R by taking advantage of a novel, proprietary expression system to generate large amounts of homogeneous CB2R. If successful, the CB2R structure would dramatically empower our current cannabinoid receptor drug discovery effort. Moreover, this structure would represent the first non-rhodopsin template for molecular modeling of Family 1 GPCRs. And, in particular, it would be an excellent template for the modeling of the closely related CB1R, involved in many therapeutic areas including drug abuse, immune disorders, and obesity. ? ?
| Salom, David; Wu, Nan; Sun, Wenyu et al. (2008) Heterologous expression and purification of the serotonin type 4 receptor from transgenic mouse retina. Biochemistry 47:13296-307 |
| Lodowski, David T; Salom, David; Le Trong, Isolde et al. (2007) Crystal packing analysis of Rhodopsin crystals. J Struct Biol 158:455-62 |
| Li, Ning; Salom, David; Zhang, Li et al. (2007) Heterologous expression of the adenosine A1 receptor in transgenic mouse retina. Biochemistry 46:8350-9 |
| Lodowski, David T; Salom, David; Le Trong, Isolde et al. (2007) Reprint of ""Crystal packing analysis of Rhodopsin crystals"" [J. Struct. Biol. 158 (2007) 455-462]. J Struct Biol 159:253-60 |
