In this work we report structural and functional studies with Smad inhibitor a basic Lys49-PLA2 from Bothrops moojeni, known as Myotoxin II or MjTX-II. B. moojeni snakes are found in central and southeastern part of the Brazil and also in some parts of Argentina, Paraguay and Bolivia, living mainly in “cerrado” and “araucaria forests” ecosystems ( Borges and Araujo, 1998). Their study have clinical and scientific importance because of the number of accidents caused by these snakes due to their aggressive behavior, their large

size compared to other snakes from the same genus and because their adaptive capacity against environmental changes ( Melgarejo, 2003). MjTX-II has 122 amino acids, molecular weight of approximately 13.5 kDa ( Lomonte et al., 1990 and Watanabe et al., 2005), and presents myotoxic activity that is characterized by increase of serum creatine kinase and morphologic changes in mice muscles selleck compound when studied in vivo and in vitro ( Stabeli et al., 2006 and Cavalcante et al., 2007). In addition, it was demonstrated that this protein presents antimicrobial, antitumoral and antiparasitic effects, having therefore potential to therapeutical applications ( Stabeli et al., 2006). Although the crystal structure of MjTX-II had been

reported in the literature in 1997 (de Azevedo et al., 1997), the article just presents the comparison of this structure with BaspTX-II (myotoxin II from Bothrops asper) that was the only Lys49-PLA2 structure known at that data. Furthermore, the authors did not deposit the coordinates of MjTX-II structure in PDB data bank making any comparison with other structures

impossible. In 2005, the structure of the complex formed Nintedanib (BIBF 1120) between MjTX-II and stearic acid was solved ( Watanabe et al., 2005), revealing the ligand binding sites and comparing it to PrTX-II/fatty acid structure that was solved in 2001 ( Lee et al., 2001). Since then, several structures of native and complexed Lys49-PLA2s have been solved revealing some consensual features of these proteins (e.g. homodimeric conformation) but bringing many controversial and intriguing issues (e.g. biological assembly, myotoxic site, the role of Lys122 residue) ( Murakami et al., 2005, dos Santos et al., 2009, Fernandes et al., 2010, Marchi-Salvador et al., 2009 and dos Santos et al., 2011b). Then, in this article we try to definitively address these issues for Lys49-PLA2s in general and to highlight some specific characteristics of MjTX-II which may be very important considering the medical and scientific importance of Lys49-PLA2s proteins for the establishment of myonecrosis. A lyophilized sample of MjTX-II was dissolved in ultra-pure water at a concentration of 11 mg mL−1.