Surface loops of extracellular phospholipase A1 determine both substrate specificity and preference for lysophospholipids

• Main Authors: Naoaki Arima, Asuka Inoue, Kumiko Makide, Takamasa Nonaka, Junken Aoki
• Format: Article
• Language: English
• Published: Elsevier 2012-03-01
• Series: Journal of Lipid Research
• Subjects: lysophospholipid; lysophospholipase; lipase; surface loop; lid; phospholipases
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520413665

Members of the pancreatic lipase family exhibit both lipase activity toward triacylglycerol and/or phospholipase A1 (PLA1) activity toward certain phospholipids. Some members of the pancreatic lipase family exhibit lysophospholipase activity in addition to their lipase and PLA1 activities. Two such enzymes, phosphatidylserine (PS)-specific PLA1 (PS-PLA1) and phosphatidic acid (PA)-selective PLA1α (PA-PLA1α, also known as LIPH) specifically hydrolyze PS and PA, respectively. However, little is known about the mechanisms that determine their substrate specificities. Crystal structures of lipases and mutagenesis studies have suggested that three surface loops, namely, β5, β9, and lid, have roles in determining substrate specificity. To determine roles of these loop structures in the substrate recognition of these PLA1 enzymes, we constructed a number of PS-PLA1 mutants in which the three surface loops are replaced with those of PA-PLA1α. The results indicate that the surface loops, especially the β5 loop, of PA-PLA1α play important roles in the recognition of PA, whereas other structure(s) in PS-PLA1 is responsible for PS preference. In addition, β5 loop of PS-PLA1 has a crucial role in lysophospholipase activity toward lysophosphatidylserine. The present study revealed the critical role of lipase surface loops, especially the β5 loop, in determining substrate specificities of PLA1 enzymes.