Author(s): Stabeli, Rodrigo Guerino ; Amui, Saulo França ; Sant'Ana, Carolina Dalaqua ; Pires, Matheus Godoy ; Nomizo, Auro ; Monteiro, Marta Chagas ; Romão, Pedro Roosevelt Torres ; Cota, Renata Guerra de Sá ; Vieira, Carlos Alberto ; Giglio, José Roberto ; Fontes, Marcos Roberto de Mattos ; Soares, Andreimar Martins
Date: 2015
Origin: Oasisbr
Subject(s): Bothrops; Chemical modification; Myotoxin; Microbial; Phospholipase
MjTX-II, a myotoxic phospholipase A2 (PLA2) homologue from Bothrops moojeni venom, was functionally and structurally characterized. The MjTX-II characterization included: (i) functional characterization (antitumoral, antimicrobial and antiparasitic effects); (ii) effects of structural modifications by 4-bromophenacyl bromide (BPB), cyanogen bromide (CNBr), acetic anhydride and 2-nitrobenzenesulphonyl fluoride (NBSF); (iii) enzymatic characterization: inhibition by low molecular weight heparin and EDTA; and (iv) molecular characterization: cDNA sequence and molecular structure prediction. The results demonstrated that MjTX-II displayed antimicrobial activity by growth inhibition against Escherichia coli and Candida albicans, antitumoral activity against Erlich ascitic tumor (EAT), human breast adenocarcinoma (SK-BR-3) and human T leukemia cells (JURKAT) and antiparasitic effects against Schistosoma mansoni and Leishmania spp., which makes MjTX-II a promising molecular model for future therapeutic applications, as well as other multifunctional homologous Lys49-PLA2s or even derived peptides. This work provides useful insights into the structural determinants of the action of Lys49-PLA2 homologues and, together with additional strategies, supports the concept of the presence of others “bioactive sites” distinct from the catalytic site in snake venom myotoxic PLA2s.
