A structure based model for liposome disruption and the role of catalytic activity in myotoxic phospholipase A2s.
Venom phospholipase A2s (PLA2s) display a wide spectrum of pharmacological activities and, based on the wealth of biochemical and structural data currently available for PLA2s, mechanistic models can now be inferred to account for some of these activities. A structural model is presented for the role played by the distribution of surface electrostatic potential in the ability of myotoxic D49/K49 PLA2s to disrupt multilamellar vesicles containing negatively charged natural and non-hydrolyzable phospholipids. Structural evidence is provided for the ability of K49 PLA2s to bind phospholipid analogues and for the existence of catalytic activity in K49 PLA2s. The importance of the existence of catalytic activity of D49 and K49 PLA2s in myotoxicity is presented.
Murakami
M T
MT
Department of Biophysics, IBILCE/UNESP, R. Cristovão Colombo 2265, CEP 15054-000, São José do Rio Preto-SP, Brazil.
Arni
R K
RK
D000818:Animals; D002384:Catalysis; D008081:Liposomes / Q000378:metabolism*; D008956:Models, Chemical; D010741:Phospholipases A / Q000378:metabolism* / Q000633:toxicity; D020836:Protein Structure, Quaternary; D012910:Snake Venoms / Q000378:metabolism* / Q000633:toxicity; D012911:Snakes; D055672:Static Electricity
D008081:Liposomes; D012910:Snake Venoms; D010741:Phospholipases A