Structure and function of extracellular phospholipase A(1) belonging to the pancreatic lipase gene family.
Phospholipase A(1) (PLA(1)) 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 PLA(1) activity in vitro. The extracellular PLA(1)s include phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)), membrane-associated phosphatidic acid (PA)-selective PLA(1)s (mPA-PLA(1)alpha and mPA-PLA(1)beta), 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 PLA(1)s differ from other members in their substrate specificities, structural features and gene organizations, and form a subfamily in the pancreatic lipase gene family. PS-PLA(1), mPA-PLA(1)alpha and mPA-PLA(1)beta exhibit only PLA(1) activity, while HL, EL and PLRP2 show triacylglycerol-hydrolyzing activity in addition to PLA(1) activity. The tertiary structures of lipases have two surface loops, the lid and the beta9 loop. The lid and the beta9 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 PLA(1)s in the two surface loops. First, lipase members exhibiting PLA(1) activity (PS-PLA(1), mPA-PLA(1)alpha and mPA-PLA(1)beta, EL, guinea pig PLRP2 and PLA(1) from hornet venom (DolmI)) have short lids. Second, PS-PLA(1), mPA-PLA(1)alpha, mPA-PLA(1)beta and DolmI, which exhibit only PLA(1) activity, have short beta9 loops. Thus, the two surface loops appear to be involved in the ligand recognition. PS-PLA(1) and mPA-PLA(1)s 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 PLA(1)s have a role in the production of these lysophospholipid mediators.[1]References
- Structure and function of extracellular phospholipase A(1) belonging to the pancreatic lipase gene family. Aoki, J., Inoue, A., Makide, K., Saiki, N., Arai, H. Biochimie (2007) [Pubmed]
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