Anal Biochem 2017 Aug 17;536:90-95. Epub 2017 Aug 17.
Center for Drug Discovery, Northeastern University, Boston, MA, 02115, United States; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, United States; Pharmaceutical Sciences Department, Northeastern University, Boston, MA, 02115, United States.
Human monoacylglycerol lipase (hMAGL) plays a key role in homeostatic tuning of the endocannabinoid signaling system and supports aggressive tumorogenesis, making this enzyme a promising therapeutic target. hMAGL features a membrane-associated lid domain that regulates entry of endocannabinoid lipid substrates into the hydrophobic channel accessing the active site, likely from the membrane bilayer. The present work applied simultaneous surface plasmon resonance and electrochemical impedance spectroscopy measurements to show that, in absence of the substrate, hMAGL can remove phospholipid molecules from the membrane and, thereby, disintegrate pre-formed, intact, tethered phospholipid bilayer membrane mimetics (tBLMs) composed of unsaturated phosphatidylcholines. Read More