Effects of chemical modification on enzymatic and toxicological properties of phospholipases A2 from Naja naja naja and Vipera russelli snake venoms.
The effects of chemical modification with 4-NN-dimethyl amino azo benzene-4'-isothiocyanate on various biological activities of phospholipases A2, NN-XIII-PLA2 from Naja naja naja and VRV-PL-VIIIa from Vipera russelli snake venoms were investigated. Modification of the enzymes resulted in significant reduction of lethal, hemolytic, anticoagulant and enzymatic activities. The Km value of the modified enzymes was increased. The modified enzymes failed to induce edema in the foot pads of mice and were non-lethal up to 16 mg/kg body weight. However, considerable myotoxicity was retained, suggesting that the toxins have multiple sites for biological activities. The aggregated form obtained from modified NN-XIII-PLA2 exhibited decreased enzymatic activity and increased toxicity compared to the modified monomer. This aggregated form did not show pyrophosphatase/phosphomonoesterase activity in contrast to the aggregated form obtained from the native NN-XIII-PLA2 molecule.
Babu
A S
AS
Department of Studies in Biochemistry, University of Mysore, Manasagangotri, India.
Gowda
T V
TV
D000469:Alkaline Phosphatase / Q000032:analysis; D000925:Anticoagulants / Q000494:pharmacology; D004546:Elapid Venoms / Q000737:chemistry* / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D017879:Isothiocyanates; D007928:Lethal Dose 50; D008970:Molecular Weight; D009135:Muscular Diseases / Q000139:chemically induced / Q000503:physiopathology; D010741:Phospholipases A / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D054467:Phospholipases A2; D011247:Pregnancy; D013050:Spectrometry, Fluorescence; D013861:Thiocyanates; D014757:Viper Venoms / Q000737:chemistry* / Q000633:toxicity; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives
D000925:Anticoagulants; D004546:Elapid Venoms; D017879:Isothiocyanates; D013861:Thiocyanates; D014757:Viper Venoms; C012926:4-(N,N-dimethylaminoazobenzene)-4'-isothiocyanate; D004124:p-Dimethylaminoazobenzene; D010741:Phospholipases A; D054467:Phospholipases A2; D000469:Alkaline Phosphatase