Crystallization of the human cannabinoid type 2 receptor

人大麻素 2 型受体的结晶

• 批准号: 7334506
• 负责人: David Salom
• 金额: $ 16.43万
• 依托单位: POLGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7334506
• 关键词: bioimaging /biomedical imaging; cannabinoid receptor; cell surface receptors; crystallization; drug design /synthesis /production; genetically modified animals; laboratory mouse; protein structure function; receptor expression; rhodopsin; structural biology; three dimensional imaging /topography

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：2 型大麻素受体 (CB2R) 是治疗神经性疼痛和几种其他疾病的靶标。解决 CB2R 的 3 维结构将有助于设计更好的 CB2R 选择性药物。尽管目前市场上的所有治疗药物中有 30-50% 调节不同 G 蛋白偶联受体 (GPCR) 的作用，但视紫红质是唯一已知其晶体结构的 GPCR。 GPCR结晶的瓶颈是难以产生晶体学所需的大量高质量受体样品。该项目的目的是通过利用新颖的专有表达系统产生大量同质 CB2R，对 CB2R 进行结晶和结构阐明。如果成功，CB2R 结构将极大地增强我们当前的大麻素受体药物发现工作。此外，该结构将代表第一个用于家族 1 GPCR 分子建模的非视紫红质模板。特别是，它将成为密切相关的 CB1R 建模的绝佳模板，涉及药物滥用、免疫紊乱和肥胖等许多治疗领域。