Crystallization of the human cannabinoid type 2 receptor

人大麻素 2 型受体的结晶

• 批准号: 7052999
• 负责人: David Salom
• 金额: $ 26万
• 依托单位: NOVASITE PHARMACEUTICALS, 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 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052999
• 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）：大麻素2型受体（CB 2 R）是治疗神经性疼痛和其他几种疾病的靶点。解决CB 2 R的三维结构将使设计更好的CB 2 R选择性药物成为可能。虽然目前市场上所有治疗药物的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晶体结构的GPCR。GPCR结晶的瓶颈一直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一种新型的专有表达系统来产生大量的同质CB 2 R，从而对CB 2 R进行结晶和结构解析。如果成功，CB 2 R结构将大大增强我们目前的大麻素受体药物发现工作。此外，该结构将代表用于家族1 GPCR的分子建模的第一个非视紫红质模板。特别是，它将是一个很好的模板，用于建模密切相关的CB 1 R，涉及许多治疗领域，包括药物滥用，免疫紊乱和肥胖。