Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family

Junken Aoki, Asuka Inoue, Kumiko Makide, Naoya Saiki, Hiroyuki Arai

Research output: Contribution to journalReview articlepeer-review

101 Citations (Scopus)

Abstract

Phospholipase A1 (PLA1) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Mammals have several enzymes that exhibit PLA1 activity in vitro. The extracellular PLA1s include phosphatidylserine (PS)-specific PLA1 (PS-PLA1), membrane-associated phosphatidic acid (PA)-selective PLA1s (mPA-PLA1α and mPA-PLA1β), hepatic lipase (HL), endothelial lipase (EL) and pancreatic lipase-related protein 2 (PLRP2), all of which belong to the pancreatic lipase gene family. The former three PLA1s differ from other members in their substrate specificities, structural features and gene organizations, and form a subfamily in the pancreatic lipase gene family. PS-PLA1, mPA-PLA1α and mPA-PLA1β exhibit only PLA1 activity, while HL, EL and PLRP2 show triacylglycerol-hydrolyzing activity in addition to PLA1 activity. The tertiary structures of lipases have two surface loops, the lid and the β9 loop. The lid and the β9 loop cover the active site in its closed conformation. An alignment of amino acid sequences of the pancreatic lipase gene family members revealed two molecular characteristics of PLA1s in the two surface loops. First, lipase members exhibiting PLA1 activity (PS-PLA1, mPA-PLA1α and mPA-PLA1β, EL, guinea pig PLRP2 and PLA1 from hornet venom (DolmI)) have short lids. Second, PS-PLA1, mPA-PLA1α, mPA-PLA1β and DolmI, which exhibit only PLA1 activity, have short β9 loops. Thus, the two surface loops appear to be involved in the ligand recognition. PS-PLA1 and mPA-PLA1s specifically hydrolyze PS and PA, respectively, producing their corresponding lysophospholipids. Lysophosphatidylserine and lysophosphatidic acid have been defined as lipid mediators with multiple biological functions. Thus, these PLA1s have a role in the production of these lysophospholipid mediators.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalBiochimie
Volume89
Issue number2
DOIs
Publication statusPublished - 2007 Feb
Externally publishedYes

Keywords

  • Lipase
  • Lysophosphatidylserine
  • Mast cells
  • Phosphatidic acid
  • Phosphatidylserine
  • Phospholipase A

ASJC Scopus subject areas

  • Biochemistry

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