Activity on insects While these toxins are well known to cause dermonecrotic lesions in mammals, little work has investigated the bioactivity of this enzyme on its natural insect prey. In a recent study, Zobel-Thropp et al. (2012) produced a recombinant toxin from a Loxosceles species and compared its enzymatic and insecticidal activity to that of crude venom. Enzymatic activities of recombinant toxins and crude venom from the same species were indistinguishable. In addition, dermonecrotic toxins and crude venom have comparable and high potency in immobilization assays on crickets. These data indicate that dermonecrotic toxins are potent insecticidal toxins. Nomenclature Several names have been given to venom dermonecrotic toxins from the Sicariidae family. By considering the biochemical aspect, the name phospholipase D (PLD) has been proposed by Lee and Lynch in 2005 to represent these enzymes that have been discovered to hydrolyse not only sphingomyelin but a more broad range of phospholipids. Hence, this term represents an accurate and broad denomination. Previously to this denomination, the name sphingomyelinase D (SMase D) was used due to its first biochemical description as enzymes capable of hydrolyzing sphingomyelin into choline and ceramide-1-phosphate (Kurpiewski et al., 1981 ). In the biological level, another name, dermonecrotic toxin is a term widely applied by toxinologists to Loxosceles enzymes, due to the hallmark of brown spider bites, which trigger dermonecrosis in mammals. Finally, the term of SicTox family members (for Sicariidae Toxin) has been given to represent the multigene family of these venom toxins that are not homologous to other enzyme families that are expressed for nonvenomous function. Hence, this term serves to emphasize this difference (Zobel-Thropp et al., 2012 ). Structure and classification These toxins vary in molecular mass from 30 to 35 kDa, and include a signal peptide followed by a propeptide. The amino acid sequences of mature toxins are highly conserved (55-99%), especially the residues essential for magnesium-ion binding and catalysis. The single polypeptide chain folds to form a distorted barrel where the inner barrel surface is lined with eight parallel β-strands linked by short flexible loops to eight α-helices that form the outer surface of the barrel (Murakami et al., 2005 ). This structural motif was first observed in the structure of the triose phosphate isomerase (TIM) and is referred to as a TIM barrel or as an (α/β)8 barrel. Based on sequence alignment, Murakami and colleagues (2006) have proposed a classification of spider venom PLD. The class I enzymes represented by SMase I from L. laeta possess a single disulfide bond and contain an extended hydrophobic loop (see entries ). All other proteins, represented by SMase D 1 from L. intermedia belong to class II, which contains an additional intrachain disulfide bond that links the shortened flexible loop with the catalytic loop (Fig.2) (see entries ). Another classification system has been proposed by Binford et al., 2009, that differs from the classes I and II classification. This classification is based on Bayesian phylogenies that support two major clades; alpha (see entries ) and beta (see entries ), within which seven and three subclades have been identified, respectively. Sequences in the alpha clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have enzymatic and dermonecrotic activities. The beta clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Figure 2: Alignment of class I PLD (represented by SMase I ) from L.laeta and class II PLD (represented by SMase D 1 ) from L.intermedia, showing the differences between class I and class II (see text). Amino acids involved in metal-ion binding and catalysis are boxed in light gray, cysteines in yellow, and the extended hydrophobic loop in blue.