EVOLUTIONARY REDUCTION OF ENZYMATIC ACTIVITIES OF SNAKE VENOM PHOSPHOLIPASES A₂

Abstract

The reaction mechanism of the 14 kDa secreted phospholipases A₂ (PLAs) and examples of venom PLAs with diminished catalytic activities are reviewed. Evolutionary strategies to reduce the venom PLA catalytic power and new function gains are discussed. Down-regulations of the enzymatic activities appear to be due to: 1) retention of interfacial binding, but with selective alternation of active site residues in basic PLAs; 2) mutations at both the interfacial binding sites and catalytic sites of strong anticoagulating PLAs which bind to the coagulation factor; and 3) either substitution or truncation of the interface binding sites in acidic subunits of heterodimeric PLA-neurotoxins to generate chaperon like molecules.

Keywords: :

• Phospholipase A2
• Snake venom toxin
• Interface binding
• Catalytic site
• Oxyanion hole
• Regulation