Aschauer_2018_Sci.Rep_8_8948

Reference

Title : The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition - Aschauer_2018_Sci.Rep_8_8948
Author(s) : Aschauer P , Zimmermann R , Breinbauer R , Pavkov-Keller T , Oberer M
Ref : Sci Rep , 8 :8948 , 2018
Abstract :

Monoacylglycerol lipases (MGLs) are enzymes that hydrolyze monoacylglycerol into a free fatty acid and glycerol. Fatty acids can be used for triacylglycerol synthesis, as energy source, as building blocks for energy storage, and as precursor for membrane phospholipids. In Mycobacterium tuberculosis, fatty acids also serve as precursor for polyketide lipids like mycolic acids, major components of the cellular envelope associated to resistance for drug. We present the crystal structure of the MGL Rv0183 from Mycobacterium tuberculosis (mtbMGL) in open conformation. The structure reveals remarkable similarities with MGL from humans (hMGL) in both, the cap region and the alpha/beta core. Nevertheless, mtbMGL could not be inhibited with JZL-184, a known inhibitor of hMGL. Docking studies provide an explanation why the activity of mtbMGL was not affected by the inhibitor. Our findings suggest that specific inhibition of mtbMGL from Mycobacterium tuberculosis, one of the oldest recognized pathogens, is possible without influencing hMGL.

PubMedSearch : Aschauer_2018_Sci.Rep_8_8948
PubMedID: 29895832
Gene_locus related to this paper: myctu-rv0183

Related information

Inhibitor JZL184
Substrate JZL184    Monoolein
Gene_locus JZL184    Monoolein    myctu-rv0183
Structure JZL184    Monoolein    myctu-rv0183    6EIC

Citations formats

Aschauer P, Zimmermann R, Breinbauer R, Pavkov-Keller T, Oberer M (2018)
The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition
Sci Rep 8 :8948

Aschauer P, Zimmermann R, Breinbauer R, Pavkov-Keller T, Oberer M (2018)
Sci Rep 8 :8948