Surface loops of extracellular phospholipase A 1 determine both substrate specificity and preference for lysophospholipids

Naoaki Arima, Asuka Inoue, Kumiko Makide, Takamasa Nonaka, Junken Aoki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Members of the pancreatic lipase family exhibit both lipase activity toward triacylglycerol and/or phospholipase A 1 (PLA 1) activity toward certain phospholipids. Some members of the pancreatic lipase family exhibit lysophospholipase activity in addition to their lipase and PLA 1 activities. Two such enzymes, phosphatidylserine (PS)-specific PLA 1 (PS-PLA 1) and phosphatidic acid (PA)-selective PLA 1α (PA-PLA 1α, 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 PLA 1 enzymes, we constructed a number of PS-PLA 1 mutants in which the three surface loops are replaced with those of PA-PLA 1α. The results indicate that the surface loops, especially the β5 loop, of PA-PLA 1α play important roles in the recognition of PA, whereas other structure(s) in PS-PLA 1 is responsible for PS preference. In addition, β5 loop of PS-PLA 1 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 PLA 1 enzymes.

Original languageEnglish
Pages (from-to)513-521
Number of pages9
JournalJournal of lipid research
Volume53
Issue number3
DOIs
Publication statusPublished - 2012 Mar

Keywords

  • Lid
  • Lipase
  • Lysophospholipase
  • Lysophospholipid
  • Phospholipases
  • Phospholipids
  • Phospholipids/phosphatidic acid
  • Phospholipids/phosphatidylserine
  • Surface loop

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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