PhTX-II a Basic Myotoxic Phospholipase A(2) from Porthidium hyoprora Snake Venom, Pharmacological Characterization and Amino Acid Sequence by Mass Spectrometry

Autor(es)

Huancahuire-Vega, Salomon ^{[1, 2]} ; Ponce-Soto, Luis Alberto ^[1] ; Marangoni, Sergio ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem, BR-13083970 Campinas, SP - Brazil

^[2] Union Peruvian Univ UPeU, Sch Med, Fac Hlth Sci, Dept Biochem & Pharmacol, Lima 15 - Peru

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 6, n. 11, p. 3077-3097, NOV 2014.
• Citações Web of Science: 4

Resumo

A monomeric basic PLA(2) (PhTX-II) of 14149.08 Da molecular weight was purified to homogeneity from Porthidium hyoprora venom. Amino acid sequence by in tandem mass spectrometry revealed that PhTX-II belongs to Asp49 PLA(2) enzyme class and displays conserved domains as the catalytic network, Ca2+-binding loop and the hydrophobic channel of access to the catalytic site, reflected in the high catalytic activity displayed by the enzyme. Moreover, PhTX-II PLA(2) showed an allosteric behavior and its enzymatic activity was dependent on Ca2+. Examination of PhTX-II PLA(2) by CD spectroscopy indicated a high content of alpha-helical structures, similar to the known structure of secreted phospholipase IIA group suggesting a similar folding. PhTX-II PLA(2) causes neuromuscular blockade in avian neuromuscular preparations with a significant direct action on skeletal muscle function, as well as, induced local edema and myotoxicity, in mice. The treatment of PhTX-II by BPB resulted in complete loss of their catalytic activity that was accompanied by loss of their edematogenic effect. On the other hand, enzymatic activity of PhTX-II contributes to this neuromuscular blockade and local myotoxicity is dependent not only on enzymatic activity. These results show that PhTX-II is a myotoxic Asp49 PLA(2) that contributes with toxic actions caused by P. hyoprora venom. (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