Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three Spider Venoms.

Spiders of genus are widely distributed and their venoms contain phospholipases D (PLDs), which degrade phospholipids and trigger inflammatory responses, dermonecrosis, hematological changes, and renal injuries. Biochemical, functional, and structural properties of three recombinant PLDs from , and , the principal species clinically relevant in South America, were analyzed. Sera against and PLDs strongly cross-reacted with other PLDs, but sera against PLD mostly reacted with homologous molecules, suggesting underlying structural and functional differences. PLDs presented a similar secondary structure profile but distinct melting temperatures. Different methods demonstrated that all PLDs cleave sphingomyelin and lysophosphatidylcholine, but and PLDs excelled. PLD showed greater "in vitro" hemolytic activity. and PLDs were more lethal in assays with mice and crickets. Molecular dynamics simulations correlated their biochemical activities with differences in sequences and conformations of specific surface loops, which play roles in protein stability and in modulating interactions with the membrane. Despite the high similarity, PLDs from and venoms are more active than PLD, requiring special attention from physicians when these two species prevail in endemic regions.