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

Mini-Symposium - Abstracts

5 STUDIES ON THE MECHANISM OF ACTION OF MYOTOXICPHOSPHOLIPASES A2 ISOLATED FROM Bothrops VENOMS

J.M. GUTIÉRREZ

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: [e-mail]

Publication Dates

• Publication in this collection
  08 Jan 1999
• Date of issue
  1997