The Mini-Symposium entitled "Myotoxins and Phospholipase A2: Structure and Biological Activity" was held at the Institute of Physics of São Carlos, of the University of São Paulo at São Carlos, State of São Paulo, Brazil, on October 16, 1996.

STUDIES ON THE MECHANISM OF ACTION OF MYOTOXIC PHOSPHOLIPASES A2 ISOLATED FROM Bothrops VENOMS

J. M. Gutiérrez(1)

(1)Clodomiro Picado Institute, School of Microbiology, University of Costa Rica, San José, Costa Rica

Various phospholipases A2 with myotoxic activity have been isolated from Bothrops snake venoms. Some of them are catalytically-active Asp-49 variants, whereas others are Lys-49 variants that either lack or have extremely low phospholipase A2 activity. The sequences and crystal structures of some of these myotoxins have been determined. In the case of Lys-49 variants, myotoxicity seems to be related to an initial perturbation in the plasma membrane of muscle fibers due to the binding and penetration of myotoxins in the bilayer. The N-terminal region seems to play a relevant pharmacological role, as well as a combination of basic and hydrophobic residues located at the C-terminal region. In addition, autocatalytic acylation might enhance the capacity of these toxins to disrupt membranes. In the case of catalytically-active variants, chemical modification studies suggest that enzymatic phospholipid degradation plays a relevant role in their mechanism of action. However, a dissociation between enzymatic and pharmacological activities has been demonstrated, suggesting the existence of a molecular region different from the catalytic network that is also responsible for membrane damage. Some results concerning the nature of a possible receptor for these myotoxins will be presented.

Financial support: Vicerrectoria de Investigación, Universidad de Costa Rica, The Third World Academy of Sciences, The International Foundation for Science and SAREC.

CORRESPONDENCE TO: Dr. Jose Maria Gutierrez - Instituto Clodomiro Picado, Universidad de Costa Rica, San Jose, Costa Rica.  Email jgutierr@cariari.ucr.ac.cr