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Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: An example of function versatility of snake venom proteins
Rodrigo G. Stábeli; Saulo F. Amui; Carolina D. Sant'Ana; Matheus G. Pires; Auro Nomizo; Marta C. Monteiro; Pedro R.T. Romão; Renata Guerra-Sá; Carlos A. Vieira; José R. Giglio; Marcos R.M. Fontes; Andreimar M. Soares
Instituto de Pesquisas em Patologias Tropicais, IPEPATRO; Universidade Federal de Rondonia, UNIR; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto-SP; Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava-PR; Laboratório de Imunoparasitologia, UNISUL, Tubarão-SC; Laboratório de Bioquímica e Biologia Molecular-Departamento de Ciências Biológicas, UFOP, Ouro Preto-MG; Departamento de Bioquímica e Imunologia, FMRP, USP, Ribeirão Preto-SP; Departamento de Física e Biofísica, IB, UNESP, Botucatu-SP, Brazil.
MjTX-II, a myotoxic phospholipase A 2 (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, antitumor 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.
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