Back to Search
Start Over
Catalytically Active Snake Venom PLA2Enzymes: An Overview of Its Elusive Mechanisms of Reaction
- Source :
- Journal of Medicinal Chemistry; April 2023, Vol. 66 Issue: 8 p5364-5376, 13p
- Publication Year :
- 2023
-
Abstract
- Snake venom-secreted phospholipase A2(svPLA2) enzymes, both catalytically active and inactive, are a central component in envenoming. These are responsible for disrupting the cell membrane’s integrity, inducing a wide range of pharmacological effects, such as the necrosis of the bitten limb, cardiorespiratory arrest, edema, and anticoagulation. Although extensively characterized, the reaction mechanisms of enzymatic svPLA2are still to be thoroughly understood. This review presents and analyses the most plausible reaction mechanisms for svPLA2,such as the “single-water mechanism” or the “assisted-water mechanism” initially proposed for the homologous human PLA2. All of the mechanistic possibilities are characterized by a highly conserved Asp/His/water triad and a Ca2+cofactor. The extraordinary increase in activity induced by binding to a lipid–water interface, known as “interfacial activation,” critical for the PLA2s activity, is also discussed. Finally, a potential catalytic mechanism for the postulated noncatalytic PLA2-like proteins is anticipated.
Details
- Language :
- English
- ISSN :
- 00222623 and 15204804
- Volume :
- 66
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Journal of Medicinal Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs62729287
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.3c00097