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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 1861 462-70 (2016)
Cited: 12 times
EuropePMC logo PMID: 26869448

Abstract

Monoglyceride lipases (MGLs) are a group of α/β-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.

Articles - 4zwn mentioned but not cited (2)

  1. Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator. Wittenborn EC, Jost M, Wei Y, Stubbe J, Drennan CL. J Biol Chem 291 25264-25277 (2016)
  2. 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 8 8948 (2018)


Articles citing this publication (10)

  1. Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride lipase. Padmanabha Das KM, Wechselberger L, Liziczai M, De la Rosa Rodriguez M, Grabner GF, Heier C, Viertlmayr R, Radler C, Lichtenegger J, Zimmermann R, Borst JW, Zechner R, Kersten S, Oberer M. J Lipid Res 59 531-541 (2018)
  2. Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism. Heier C, Taschler U, Radulovic M, Aschauer P, Eichmann TO, Grond S, Wolinski H, Oberer M, Zechner R, Kohlwein SD, Zimmermann R. J Biol Chem 291 11865-11875 (2016)
  3. Contribution of the Oligomeric State to the Thermostability of Isoenzyme 3 from Candida rugosa. Álvarez-Cao ME, González R, Pernas MA, Rúa ML. Microorganisms 6 E108 (2018)
  4. A Thermostable Monoacylglycerol Lipase from Marine Geobacillus sp. 12AMOR1: Biochemical Characterization and Mutagenesis Study. Tang W, Lan D, Zhao Z, Li S, Li X, Wang Y. Int J Mol Sci 20 E780 (2019)
  5. Study on a Novel Cold-Active and Halotolerant Monoacylglycerol Lipase Widespread in Marine Bacteria Reveals a New Group of Bacterial Monoacylglycerol Lipases Containing Unusual C(A/S)HSMG Catalytic Motifs. Li PY, Zhang YQ, Zhang Y, Jiang WX, Wang YJ, Zhang YS, Sun ZZ, Li CY, Zhang YZ, Shi M, Song XY, Zhao LS, Chen XL. Front Microbiol 11 9 (2020)
  6. The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase. Kim HJ, Lee BJ, Kwon AR. J Lipid Res 61 722-733 (2020)
  7. The herbicide quinclorac as potent lipase inhibitor: Discovery via virtual screening and in vitro/in vivo validation. Dahabiyeh LA, Bustanji Y, Taha MO. Chem Biol Drug Des 93 787-797 (2019)
  8. Structural Changes in the Cap of Rv0183/mtbMGL Modulate the Shape of the Binding Pocket. Grininger C, Leypold M, Aschauer P, Pavkov-Keller T, Riegler-Berket L, Breinbauer R, Oberer M. Biomolecules 11 1299 (2021)
  9. Structure and Dynamics of an Archeal Monoglyceride Lipase from Palaeococcus ferrophilus as Revealed by Crystallography and In Silico Analysis. Labar G, Brandt N, Flaba A, Wouters J, Leherte L. Biomolecules 11 533 (2021)
  10. Discovery of a non-canonical prototype long-chain monoacylglycerol lipase through a structure-based endogenous reaction intermediate complex. Pinotsis N, Krüger A, Tomas N, Chatziefthymiou SD, Litz C, Mortensen SA, Daffé M, Marrakchi H, Antranikian G, Wilmanns M. Nat Commun 14 7649 (2023)


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