Structure and function of phosphatidylserine-specific phospholipase A1.
Phospholipase A1 (PLA1) is an enzyme that hydrolyzes the sn-1 fatty acids from phospholipids and produces 2-acyl-lysophospholipids. Although PLA1 activities are detected in many tissues and cell lines, a limited number of PLA1s have been purified and cloned so far. These include phosphatidylserine (PS)-specific PLA1 (PS-PLA1) from rat platelets, PLA1 from vespid venom, and phosphatidic acid (PA)-preferential PLA1 (PA-PLA1). Structurally, the former two PLA1s belong to the lipase family, where they form a subfamily among the lipase family. An alignment of the PLA1s with other members of the lipase family revealed two molecular characteristics of PLA1: the presence of extremely short lids and deleted beta9 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-PLA1 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-PLA1 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-PLA1 reveals the presence of PLA1 subfamily within the lipase family and suggests that PLA1 has a role in the production of lysophospholipid mediators.
Aoki
Junken
J
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan. jaoki@mol.f.u-tokyo.ac.jp
Nagai
Yuki
Y
Hosono
Hiroyuki
H
Inoue
Keizo
K
Arai
Hiroyuki
H
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054466:Phospholipases A1; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
C512665:PLA1A protein, human; D010741:Phospholipases A; D054466:Phospholipases A1; C512667:Pla1a protein, rat