4ZXF

Crystal Structure of a Soluble Variant of Monoglyceride Lipase from Saccharomyces Cerevisiae in Complex with a Substrate Analog

Summary for 4ZXF

• Entry DOI: 10.2210/pdb4zxf/pdb
• Related: 4ZWN
• Descriptor: Monoglyceride lipase, SULFATE ION, 1-{3-[(R)-hydroxy(octadecyloxy)phosphoryl]propyl}triaza-1,2-dien-2-ium, ... (5 entities in total)
• Functional Keywords: hydrolase, monoglyceride lipase, monoacylglycerol lipase, complex, substrate analog
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• Cellular location: Cytoplasm: P28321
• Total number of polymer chains: 4
• Total formula weight: 156355.16

Authors

Aschauer, P.,Lichtenegger, J.,Rengachari, S.,Gruber, K.,Oberer, M. (deposition date: 2015-05-20, release date: 2016-05-25, Last modification date: 2024-01-10)

Primary citation

Aschauer, P.,Rengachari, S.,Lichtenegger, J.,Schittmayer, M.,Das, K.M.,Mayer, N.,Breinbauer, R.,Birner-Gruenberger, R.,Gruber, C.C.,Zimmermann, R.,Gruber, K.,Oberer, M.
Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p.
Biochim.Biophys.Acta, 1861:462-470, 2016

PubMed 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.

PubMed: 26869448
DOI: 10.1016/j.bbalip.2016.02.005

Experimental method

X-RAY DIFFRACTION (2.5 Å)