A Binding Site for Nonsteroidal Anti-inflammatory Drugs in Fatty Acid Amide Hydrolase
详细信息 查看全文
- 作者：Laura Bertolacci ; Elisa Romeo ; Marina Veronesi ; Paola Magotti ; Clara Albani ; Mauro Dionisi ; Chiara Lambruschini ; Rita Scarpelli ; Andrea Cavalli ; Marco De Vivo ; Daniele Piomelli ; Gianpiero Garau
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：January 9, 2013
- 年：2013
- 卷：135
- 期：1
- 页码：22-25
- 全文大小：264K
- 年卷期：v.135,no.1(January 9, 2013)
- ISSN：1520-5126
文摘
In addition to inhibiting the cyclooxygenase (COX)-mediated biosynthesis of prostanoids, various widely used nonsteroidal anti-inflammatory drugs (NSAIDs) enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH). The X-ray structure of FAAH in complex with the NSAID carprofen, along with site-directed mutagenesis, enzyme activity assays, and NMR analysis, has revealed the molecular details of this interaction, providing information that may guide the design of dual FAAH鈥揅OX inhibitors with superior analgesic efficacy.