6eic
From Proteopedia
Crystal structure of Rv0183, a Monoglyceride Lipase from Mycobacterium Tuberculosis
Structural highlights
FunctionMGLL_MYCTU Involved in the hydrolysis of exogenous host lipids during chronic infection. Catalyzes the hydrolysis of both monoacylglycerols (MAG) and diacylglycerols (DAG). It hydrolyzes 2-MAG, 1-3-MAG and MAG with short, medium and long chain fatty acids such as 1-monobutyroyl-rac-glycerol (MC4), 1-mono-octanoyl-rac-glycerol (MC8), 1-monodecanoyl-rac-glycerol (MC10), 1-monolauroyl-rac-glycerol (MC12), 1-monomyristoyl-rac-glycerol (MC14) and 1-mono-oleyl-rac-glycerol (MC18:1) (PubMed:17784850). Also able to hydrolyze DAG with short (DiC6) and medium (DiC10) fatty acid chains, but not whith a longest chain fatty acids (PubMed:17784850). Can also hydrolyze vinyl laurate (VC12), vinyl butyrate (VC4) and vinyl propionate (VC3) (PubMed:17784850).[1] [2] Publication Abstract from PubMedMonoacylglycerol 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. The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition.,Aschauer P, Zimmermann R, Breinbauer R, Pavkov-Keller T, Oberer M Sci Rep. 2018 Jun 12;8(1):8948. doi: 10.1038/s41598-018-27051-7. PMID:29895832[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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