[Role of arginine and histidine residues in the biological activity of botulinic neurotoxin A].
Treatment of botulinic neurotoxin A with cyclohexanedione demonstrated that modification of 5 to 10 arginine residues does not change the neurotoxin toxicity, while after modification of 15-20 arginine residues the toxicity is decreased by 40-50% of the original value. Butanedione exerts a stronger detoxicating effect on neurotoxin than cyclohexanedione. The molecular conformation of the modified toxin derivatives and their precipitability upon interaction with antisera against toxin and toxin fragments does not change thereby. The non-toxic derivatives of toxin containing 40 modified arginine residues possess a partial serological affinity for the original toxin in a reaction with antiserum against toxin but do not interact with the antifragment sera. The molecular conformation of these preparations is changed considerably. It is assumed that one or two arginine residues are located near the toxic site of the neurotoxin molecule and are also components of its antigenic determinants. Modification of histidine residues in the neurotoxin molecule by diethylpyrocarbonate is accompanied by a decrease of its toxicity. An additional 10% toxicity is revealed upon modification of 11-13 histidine residues. The molecular conformation of the modified derivatives of neurotoxin and their precipitability do not change thereby. It is probable that 1 or 2 histidine residues are located at or near the toxic site. The data obtained suggest that histidine residues are not localized in antigenic determinants of the neurotoxin molecule.
D000818:Animals; D001120:Arginine; D001905:Botulinum Toxins / Q000633:toxicity*; D003512:Cyclohexanones / Q000494:pharmacology; D003931:Diacetyl / Q000494:pharmacology; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis; D006639:Histidine; D011487:Protein Conformation
D003512:Cyclohexanones; D000939:Epitopes; D006639:Histidine; C018031:1,2-cyclohexanedione; D001120:Arginine; D001905:Botulinum Toxins; D003931:Diacetyl; D004047:Diethyl Pyrocarbonate
Rol' ostatkov arginina i gistidina v biologicheskoĭ aktivnosti botulinicheskogo neĭrotoksina tipa A.