title: Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa reveals a novel lid conformation and insights into the substrate specificity.
abstract: Most lipases contain a lid domain to shield the hydrophobic binding site from the water environment. The lid, mostly in helical form, can undergo a conformational change to expose the active cleft during the interfacial activation. Here we report the crystal structures of Malassezia globosa LIP1 (SMG1) at 1.45 and 2.60 Å resolution in two crystal forms. The structures present SMG1 in its closed form, with a novel lid in loop conformation. SMG1 is one of the few members in the fungal lipase family that has been found to be strictly specific for mono- and diacylglycerol. To date, the mechanism for this substrate specificity remains largely unknown. To investigate the substrate binding properties, we built a model of SMG1 in open conformation. Based on this model, we found that the two bulky hydrophobic residues adjacent to the catalytic site and the N-terminal hinge region of the lid both may act as steric hindrances for triacylglycerols binding. These unique structural features of SMG1 will provide a better understanding on the substrate specificity of mono- and diacylglycerol lipases and a platform for further functional study of this enzyme.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230026, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Shulin
authors.initials: S
authors.lastname: Hou
authors.forename: Jinxin
authors.initials: J
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D008071:Lipoprotein Lipase / Q000737:chemistry / Q000378:metabolism*; D008290:Malassezia / Q000201:enzymology*; D008994:Monoacylglycerol Lipases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase