4.6 Article

Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2016.02.005

Keywords

Monoglyceride lipase; Monoacylglycerol lipase; Crystal structure; Lipase-substrate-complex; Lipase cap; Substrate specificity

Funding

  1. Doctoral School DK Molecular Enzymology [W901-B12]
  2. FWF [P24857]
  3. SFB Lipotox - Austrian Science Fund (FWF) [F30]
  4. NAWI Graz
  5. NIGMS [P41-GM103311]
  6. European Community's Seventh Framework Programme under BioStruct-X [283570]
  7. Austrian Science Fund (FWF) [P24857] Funding Source: Austrian Science Fund (FWF)
  8. Austrian Science Fund (FWF) [W 901, P 24857, P 26074] Funding Source: researchfish

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Monoglyceride 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. (C) 2016 The Authors. Published by Elsevier B.V.

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