Purification, crystallization and preliminary X-ray diffraction analysis of a soluble variant of the monoglyceride lipase Yju3p from the yeast<i>Saccharomyces cerevisiae</i>

Rengachari, Srinivasan; Aschauer, P.; Sturm, Christian; Oberer, Monika

doi:10.1107/s2053230x15001557

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…1A ). Monomeric forms of MGLs have also been observed experimentally for bMGL 26 and Yju3p 33 . PISA analysis of human MGL (PDB ID 3PE6 23 ,) indicates that hMGL may form a dimer in solution consistent with literature reports using gel filtration chromatography 25 .…”

Section: Resultsmentioning

confidence: 63%

The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition

Aschauer

Zimmermann

Breinbauer

et al. 2018

Sci Rep

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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 α/β 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.

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Section: Resultsmentioning

confidence: 63%

The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition

Aschauer

Zimmermann

Breinbauer

et al. 2018

Sci Rep

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Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p

Aschauer

Rengachari

Lichtenegger

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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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.

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Purification, crystallization and preliminary X-ray diffraction analysis of a soluble variant of the monoglyceride lipase Yju3p from the yeastSaccharomyces cerevisiae

Cited by 2 publications

References 26 publications

The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition

The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition

Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p

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