Bracey Michael H, Hanson Michael A, Masuda Kim R, Stevens Raymond C, Cravatt Benjamin F
Department of Cell Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2002 Nov 29;298(5599):1793-6. doi: 10.1126/science.1076535.
Cellular communication in the nervous system is mediated by chemical messengers that include amino acids, monoamines, peptide hormones, and lipids. An interesting question is how neurons regulate signals that are transmitted by membrane-embedded lipids. Here, we report the 2.8 angstrom crystal structure of the integral membrane protein fatty acid amide hydrolase (FAAH), an enzyme that degrades members of the endocannabinoid class of signaling lipids and terminates their activity. The structure of FAAH complexed with an arachidonyl inhibitor reveals how a set of discrete structural alterations allows this enzyme, in contrast to soluble hydrolases of the same family, to integrate into cell membranes and establish direct access to the bilayer from its active site.
神经系统中的细胞通讯由化学信使介导，这些化学信使包括氨基酸、单胺、肽类激素和脂质。一个有趣的问题是神经元如何调节由膜嵌入脂质传递的信号。在此，我们报告了整合膜蛋白脂肪酸酰胺水解酶（FAAH）的2.8埃晶体结构，该酶可降解内源性大麻素类信号脂质成员并终止其活性。与花生四烯酰基抑制剂复合的FAAH结构揭示了一组离散的结构改变如何使该酶与同一家族的可溶性水解酶不同，能够整合到细胞膜中并从其活性位点直接进入脂双层。
