TY - JOUR
T1 - Malassezia globosa MgMDL2 lipase
T2 - Crystal structure and rational modification of substrate specificity
AU - Lan, Dongming
AU - Xu, Huan
AU - Xu, Jinxin
AU - Dubin, Grzegorz
AU - Liu, Jinsong
AU - Iqbal Khan, Faez
AU - Wang, Yonghua
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6/24
Y1 - 2017/6/24
N2 - Lipases play an important role in physiological metabolism and diseases, and also have multiple industrial applications. Rational modification of lipase specificity may increase the commercial utility of this group of enzymes, but is hindered by insufficient mechanistic understanding. Here, we report the 2.0 Å resolution crystal structure of a mono- and di-acylglycerols lipase from Malassezia globosa (MgMDL2). Interestingly, residues Phe278 and Glu282 were found to involve in substrate recognition because mutation on each residue led to convert MgMDL2 to a triacylglycerol (TAG) lipase. The Phe278Ala and Glu282Ala mutants also acquired ability to synthesize TAGs by esterification of glycerol and fatty acids. By in silicon analysis, steric hindrance of these residues seemed to be key factors for the altered substrate specificity. Our work may shed light on understanding the unique substrate selectivity mechanism of mono- and di-acylglycerols lipases, and provide a new insight for engineering biocatalysts with desired catalytic behaviors for biotechnological application.
AB - Lipases play an important role in physiological metabolism and diseases, and also have multiple industrial applications. Rational modification of lipase specificity may increase the commercial utility of this group of enzymes, but is hindered by insufficient mechanistic understanding. Here, we report the 2.0 Å resolution crystal structure of a mono- and di-acylglycerols lipase from Malassezia globosa (MgMDL2). Interestingly, residues Phe278 and Glu282 were found to involve in substrate recognition because mutation on each residue led to convert MgMDL2 to a triacylglycerol (TAG) lipase. The Phe278Ala and Glu282Ala mutants also acquired ability to synthesize TAGs by esterification of glycerol and fatty acids. By in silicon analysis, steric hindrance of these residues seemed to be key factors for the altered substrate specificity. Our work may shed light on understanding the unique substrate selectivity mechanism of mono- and di-acylglycerols lipases, and provide a new insight for engineering biocatalysts with desired catalytic behaviors for biotechnological application.
KW - Crystal structure
KW - Mono- and di-acylglycerol lipase
KW - Rational modification
KW - Site-directed mutagenesis
UR - http://www.scopus.com/inward/record.url?scp=85018937871&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.04.103
DO - 10.1016/j.bbrc.2017.04.103
M3 - Article
C2 - 28433636
AN - SCOPUS:85018937871
SN - 0006-291X
VL - 488
SP - 259
EP - 265
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -