Labar_2010_Chembiochem_11_218

Reference

Title : Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling - Labar_2010_Chembiochem_11_218
Author(s) : Labar G , Bauvois C , Borel F , Ferrer JL , Wouters J , Lambert DM
Ref : Chembiochem , 11 :218 , 2010
Abstract :

2-Arachidonoylglycerol plays a major role in endocannabinoid signaling, and is tightly regulated by the monoacylglycerol lipase (MAGL). Here we report the crystal structure of human MAGL. The protein crystallizes as a dimer, and despite structural homologies to haloperoxidases and esterases, it distinguishes itself by a wide and hydrophobic access to the catalytic site. An apolar helix covering the active site also gives structural insight into the amphitropic character of MAGL, and likely explains how MAGL interacts with membranes to recruit its substrate. Docking of 2-arachidonoylglycerol highlights a hydrophobic and a hydrophilic cavity that accommodate the lipid into the catalytic site. Moreover, we identified Cys201 as the crucial residue in MAGL inhibition by N-arachidonylmaleimide, a sulfhydryl-reactive compound. Beside the advance in the knowledge of endocannabinoids degradation routes, the structure of MAGL paves the way for future medicinal chemistry works aimed at the design of new drugs exploiting 2-arachidonoylglycerol transmission.

PubMedSearch : Labar_2010_Chembiochem_11_218
PubMedID: 19957260
Gene_locus related to this paper: human-MGLL

Related information

Citations formats

Labar G, Bauvois C, Borel F, Ferrer JL, Wouters J, Lambert DM (2010)
Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling
Chembiochem 11 :218

Labar G, Bauvois C, Borel F, Ferrer JL, Wouters J, Lambert DM (2010)
Chembiochem 11 :218