3HJU

Crystal structure of human monoglyceride lipase

Summary for 3HJU

• Entry DOI: 10.2210/pdb3hju/pdb
• Descriptor: Monoglyceride lipase, GLYCEROL (3 entities in total)
• Functional Keywords: alpha/beta hydrolase, hydrolase, serine esterase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 75580.32

Authors

Labar, G.,Bauvois, C.,Borel, F.,Ferrer, J.-L.,Wouters, J.,Lambert, D.M. (deposition date: 2009-05-22, release date: 2009-12-08, Last modification date: 2024-04-03)

Primary citation

Labar, G.,Bauvois, C.,Borel, F.,Ferrer, J.-L.,Wouters, J.,Lambert, D.M.
Crystal Structure of the Human Monoacylglycerol Lipase, a Key Actor in Endocannabinoid Signaling
Chembiochem, 11:218-227, 2010

PubMed 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.

PubMed: 19957260
DOI: 10.1002/cbic.200900621

Experimental method

X-RAY DIFFRACTION (2.2 Å)