Membrane phospholipid bilayer as a determinant of monoacylglycerol lipase kinetic profile and conformational repertoire.

ABSTRACT: The membrane-associated serine hydrolase, monoacylglycerol lipase (MGL), is a well-recognized therapeutic target that regulates endocannabinoid signaling. Crystallographic studies, while providing structural information about static MGL states, offer no direct experimental insight into the impact of MGL's membrane association upon its structure-function landscape. We report application of phospholipid bilayer nanodiscs as biomembrane models with which to evaluate the effect of a membrane system on the catalytic properties and conformational dynamics of human MGL (hMGL). Anionic and charge-neutral phospholipid bilayer nanodiscs enhanced hMGL's kinetic properties [apparent maximum velocity (Vmax) and substrate affinity (Km)]. Hydrogen exchange mass spectrometry (HX MS) was used as a conforma

SUBMITTER: Nasr ML 

PROVIDER: S-EPMC3690717 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature