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. Included in this family are Vespid venom allergen phospholipase A1. Vespid phospholipase A1 (vPLA1) is one of the primary venom components with local inflammatory effects. In addition to causing allergic reactions, vPLA1 can hydrolyze the sn-1 fatty acids in phospholipids and convert them into their corresponding lyso compounds. vPLA1 may disrupt the phospholipid packing of biological membranes, causing severe hemolysis and leading to cardiac dysfunction and death in animals
Title: Crystal structure of vespid phospholipase A1 reveals insights into the mechanism for cause of membrane dysfunction Hou MH, Chuang CY, Ko TP, Hu NJ, Chou CC, Shih YP, Ho CL, Wang AH Ref: Insect Biochemistry & Molecular Biology, 68:79, 2016 : PubMed
Vespid phospholipase A1 (vPLA1) from the black-bellied hornet (Vespa basalis) catalyzes the hydrolysis of emulsified phospholipids and shows potent hemolytic activity that is responsible for its lethal effect. To investigate the mechanism of vPLA1 towards its function such as hemolysis and emulsification, we isolated vPLA1 from V. basalis venom and determined its crystal structure at 2.5 A resolution. vPLA1 belongs to the alpha/beta hydrolase fold family. It contains a tightly packed beta-sheet surrounded by ten alpha-helices and a Gly-X-Ser-X-Gly motif, characteristic of a serine hydrolyase active site. A bound phospholipid was modeled into the active site adjacent to the catalytic Ser-His-Asp triad indicating that Gln95 is located at hydrogen-bonding distance from the substrate's phosphate group. Moreover, a hydrophobic surface comprised by the side chains of Phe53, Phe62, Met91, Tyr99, Leu197, Ala167 and Pro169 may serve as the acyl chain-binding site. vPLA1 shows global similarity to the N-terminal domain of human pancreatic lipase (HPL), but with some local differences. The lid domain and the beta9 loop responsible for substrate selectivity in vPLA1 are shorter than in HPL. Thus, solvent-exposed hydrophilic residues can easily accommodate the polar head groups of phospholipids, thereby accounting for the high activity level of vPLA1. Our result provides a potential explanation for the ability of vPLA1 to hydrolyze phospholipids of cell membrane.
In addition to causing allergic reactions, vPLA1 can hydrolyze the sn-1 fatty acids in phospholipids and convert them into their corresponding lyso compounds. vPLA1 may disrupt the phospholipid packing of biological membranes, causing severe hemolysis and leading to cardiac dysfunction and death in animals