C. 3.1.1.4) are regarded as one of the most important protein classes. PLA2s are enzymes that catalyze the hydrolysis of 2-acyl ester bonds of 3-sn-phospholipids producing fatty acids and lysophospholipids ( Gutiérrez and Lomonte, 1997). In addition to their catalytic role, they show a wide variety of pharmacological activities, such as neurotoxicity, myotoxicity, anticoagulant and cardiotoxicity ( de Paula et al., 2009). An analysis of the B. jararacussu venom gland transcriptome

showed that 35% of transcripts are PLA2s with 83% encoding BthTX-I (Bothropstoxin-I, a basic Lys49-PLA2), 8% BthTX-II (Bothropstoxin-II, a basic Asp49-PLA2) and 9% BthA-I (Acidic Asp49-PLA2) ( Kashima et al., 2004). A large number of PLA2s have been purified, characterized and several three dimensional structures have been solved for PLA2s from the Bothrops genus selleck chemicals llc (revised by Stábeli et al., 2012). Correlative studies have been performed with the predicted structures to understand the sites of pharmacological activity ( Soares et al., 2001, Lomonte et al., 2003, Soares and Giglio, 2003, Murakami et al., 2007, Montecucco et al., 2008 and Teixeira et al., 2011). The PLA2s as a family are intriguing because despite the significant sequence and structural find protocol similarities between members, they present a diverse spectrum of activities, which may or may not be related to their

primary catalytic activity ( Higuchi et al., 2007 and Tsai et al., 2007). This diverse pharmacological profile is suggested to have been acquired through evolution by a positive darwinian selection in the protein-coding exons by an accelerated evolutionary process that has resulted in many variants with diverse pharmacological effects ( Ohno et al., 1998). The superfamily of PLA2 can be divided into five principal groups of enzymes: the secreted PLA2s (sPLA2s), the cytosolic PLA2s (cPLA2s), the Ca2+-independent PLA2s (iPLA2s), the platelet-activating factor acetylhydrolases (PAF-AH) and the lysosomal PLA2s (Schaloske and Dennis, 2006). The sPLA2s are further subdivided into seventeen classifications according to their molecular mass and the number

of disulfide bonds (Schaloske and Dennis, 2006). The Dolichyl-phosphate-mannose-protein mannosyltransferase snake (Viperidae) venom PLA2s (svPLA2s) are classified as GIIA, which contain seven disulfide bonds and have a molecular mass around 13–15 kDa (Schaloske and Dennis, 2006). The GIIA svPLA2s can be further subdivided into two main types according to the amino acid residue in the 49th position: Asp49-PLA2 and Lys49-PLA2 (Arni and Ward, 1996). The Asp49-PLA2s are the enzymes responsible for cellular membrane disruption through Ca2+-dependent hydrolysis of phospholipids with myotoxicity activity or not. The Lys49-PLA2s do not display catalytic activity, but can exert a pronounced and localized myotoxic effect that is not neutralized by antivenom therapy (Howard and Gundersen, 1980 and Chang, 1985). In 1911, Brazil demonstrated that the action of the B.