Structure and function of phosphatidylserine-specific phospholipase A1

Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes the sn-1 fatty acids from phospholipids and produces 2-acyl-lysophospholipids. Although PLA(1) activities are detected in many tissues and cell lines, a limited number of PLA(1)s have been purified and cloned so far. These include phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)) from rat platelets, PLA(1) from vespid venom, and phosphatidic acid (PA)preferential PLA(1) (PA-PLA(1)). Structurally, the former two PLA(1)s belong to the lipase family, where they form a subfamily among the lipase family. An alignment of the PLA(1)s with other members of the lipase family revealed two molecular characteristics of PLA(1): the presence of extremely short lids and deleted 139 loops. The two surface loops have been implicated in the ligand recognition in human pancreatic lipase (PL) and guinea pig PL-related protein 2. Under physiological conditions, accessibility of PS-PLA(1) to its substrate is limited as it is a secreted enzyme and PS is normally located in the inner leaflet of the lipid bilayer. However, PS-PLA(1) efficiently hydrolyzes PS exposed on the surface of cells such as apoptotic cells and activated platelets, and produces 2-acyl-lysophosphatidylserine (lysoPS), which is a lipid mediator for mast cells, T cells and neural cells. Identification of PS-PLA(1) reveals the presence of PLA, subfamily within the lipase family and suggests that PLA(1) has a role in the production of lysophospholipid mediators. (C) 2002 Elsevier Science B.V. All rights reserved.