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Crystal Structure of a Soluble Variant of Monoglyceride Lipase from Saccharomyces Cerevisiae in Complex with a Substrate Analog
Structural highlights
FunctionMGLL_YEAST Converts monoacylglycerides (MAG) to free fatty acids and glycerol. Required for efficient degradation of MAG, short-lived intermediates of glycerolipid metabolism which may also function as lipid signaling molecules. Controls inactivation of the signaling lipid N-palmitoylethanolamine (PEA).[1] [2] Publication Abstract from PubMedMonoglyceride lipases (MGLs) are a group of alpha/beta-hydrolases that catalyze the hydrolysis of monoglycerides (MGs) into free fatty acids and glycerol. This reaction serves different physiological functions, namely in the last step of phospholipid and triglyceride degradation, in mammalian endocannabinoid and arachidonic acid metabolism, and in detoxification processes in microbes. Previous crystal structures of MGLs from humans and bacteria revealed conformational plasticity in the cap region of this protein and gave insight into substrate binding. In this study, we present the structure of a MGL from Saccharomyces cerevisiae called Yju3p in its free form and in complex with a covalently bound substrate analog mimicking the tetrahedral intermediate of MG hydrolysis. These structures reveal a high conservation of the overall shape of the MGL cap region and also provide evidence for conformational changes in the cap of Yju3p. The complex structure reveals that, despite the high structural similarity, Yju3p seems to have an additional opening to the substrate binding pocket at a different position compared to human and bacterial MGL. Substrate specificities towards MGs with saturated and unsaturated alkyl chains of different lengths were tested and revealed highest activity towards MG containing a C18:1 fatty acid. Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p.,Aschauer P, Rengachari S, Lichtenegger J, Schittmayer M, Das KM, Mayer N, Breinbauer R, Birner-Gruenberger R, Gruber CC, Zimmermann R, Gruber K, Oberer M Biochim Biophys Acta. 2016 May;1861(5):462-70. doi: 10.1016/j.bbalip.2016.02.005., Epub 2016 Feb 9. PMID:26869448[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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