Chemical Modi cations of PhTX-I Myoto in from Porthidium hyoprora Snake Venom: Effects on Structural, Enzymatic, and Pharmacological Properties

Autor(es)

Huancahuire-Vega, Salomon ; Correa, Daniel H. A. ; Hollanda, Luciana M. ; Lancellotti, Marcelo ; Ramos, Carlos H. I. ; Ponce-Soto, Luis Alberto ; Marangoni, Sergio

• Tipo de documento: Artigo Científico
• Fonte: BIOMED RESEARCH INTERNATIONAL; v. 2013, p. 12-pg., 2013-01-01.

Resumo

We recently described the isolation of a basic PLA2 (PhTX-I) from Porthidium hyoprora snake venom.. is toxin exhibits high catalytic activity, induces in vivo myotoxicity, moderates footpad edema, and causes in vitro neuromuscular blockade. Here, we describe the chemical modifications of specific amino acid residues (His, Tyr, Lys, and Trp), performed in PhTX-I, to study their effects on the structural, enzymatic, and pharmacological properties of this myotoxin. After chemical treatment, a single His, 4 Tyr, 7 Lys, and one Trp residues were modified. The secondary structure of the protein remained unchanged as measured by circular dichroism; however other results indicated the critical role played by Lys and Tyr residues in myotoxic, neurotoxic activities and mainly in the cytotoxicity displayed by PhTX-I. His residue and therefore catalytic activity of PhTX-I are relevant for edematogenic, neurotoxic, and myotoxic effects, but not for its cytotoxic activity. This dissociation observed between enzymatic activity and some pharmacological effects suggests that other molecular regions distinct from the catalytic site may also play a role in the toxic activities exerted by this myotoxin. Our observations supported the hypothesis that both the catalytic sites as the hypothetical pharmacological sites are relevant to the pharmacological profile of PhTX-I. (AU)

• Processo FAPESP: 09/51207-9 - Avaliacao das atividades miotoxica, neurotoxica, citotoxica e inflamatoria induzidas por miotoxinas e neurotoxinas fosfolipase a2 isoladas de veneno de porthidium hyoprora
• Beneficiário: Salomon Huancahuire Vega
• Modalidade de apoio: Bolsas no Brasil - Doutorado