PT  - JOURNAL ARTICLE
ED  - , 
TI  - Degrading the Signal Lipids
AID  - 10.1126/stke.2002.161.tw455
DP  - 2002 Dec 03
TA  - Science's STKE
PG  - tw455--tw455
VI  - 2002
IP  - 161
4099  - http://stke.sciencemag.org/content/2002/161/tw455.short
4100  - http://stke.sciencemag.org/content/2002/161/tw455.full
SO  - Sci. STKE2002 Dec 03; 2002
AB  - Endocannabinoid signaling lipids bind to the cannabinoid receptor and modulate behaviors such as pain and cognition. Their activity is terminated when the lipids are degraded by the integral membrane protein fatty acid amide hydrolase (FAAH). Now Bracey et al. have determined the structure of FAAH bound to an inhibitor at 2.8-angstrom resolution. The structure is similar to soluble hydrolases in the same family, but key differences allow integration into membranes and create a binding pocket for the hydrophobic substrate. The active site is near the membrane surface and has direct access both to the lipid bilayer and the cytoplasm so that signaling lipids can enter the active site from the membrane and polar amine products could exit into the cytoplasm. M. H. Bracey, M. A. Hanson, K. R. Masuda, R. C. Stevens, B. F. Cravatt, Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science 298, 1793-1796 (2002). [Abstract] [Full Text]