Structure Report for: 4ZWN

Aschauer, P., Rengachari, S., Gruber, K., Oberer, M.

Title: 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 and Oberer M <2 more author(s)> 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 (- 2)
Ref: Biochimica & Biophysica Acta, 1861:462, 2016 : PubMed
Abstract


ESTHER: Aschauer_2016_Biochim.Biophys.Acta_1861_462
PubMedSearch: Aschauer 2016 Biochim.Biophys.Acta 1861 462
PubMedID: 26869448
Gene_locus related to this paper: yeast-mgll
Inhibitor(s) related to this paper: C18-octadecyl-MAG-like-phosphonate

Abstract

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.



        

Title: Purification, crystallization and preliminary X-ray diffraction analysis of a soluble variant of the monoglyceride lipase Yju3p from the yeast Saccharomyces cerevisiae
Rengachari S, Aschauer P, Sturm C, Oberer M
Ref: Acta Crystallographica F Struct Biol Commun, 71:243, 2015 : PubMed
Abstract


ESTHER: Rengachari_2015_Acta.Crystallogr.F.Struct.Biol.Commun_71_243
PubMedSearch: Rengachari 2015 Acta.Crystallogr.F.Struct.Biol.Commun 71 243
PubMedID: 25664804
Gene_locus related to this paper: yeast-mgll
Inhibitor(s) related to this paper: C18-octadecyl-MAG-like-phosphonate

Abstract

The protein Yju3p is the orthologue of monoglyceride lipases in the yeast Saccharomyces cerevisiae. A soluble variant of this lipase termed s-Yju3p (38.3 kDa) was generated and purified to homogeneity by affinity and size-exclusion chromatography. s-Yju3p was crystallized in a vapour-diffusion setup at 293 K and a complete data set was collected to 2.4 A resolution. The crystal form was orthorhombic (space group P212121), with unit-cell parameters a = 77.2, b = 108.6, c = 167.7 A. The asymmetric unit contained four molecules with a solvent content of 46.4%.