The positive charge concentrated at the C-terminal region of ammodytoxin (Atx) A, which is involved in presynaptic toxicity, has been reversed. A six-site mutant of AtxA (K108N/K111N/K127T/K128E/E129T/K132E, where K108N = Lys108 → Asn etc.) was prepared, in which five out of seven C-terminal basic amino acid residues were substituted with neutral or acidic ones. The mutant was approximately 30-fold less lethal, but still neurotoxic. Consistent with this, its binding affinity for the neuronal receptors decreased by only a factor of five. Additionally, a single-site mutant of AtxA was prepared, with substitution at only one position (K127T) out of six mutated in the six-site mutant. Its toxicity indicated that most, if not all, of the six mutated residues partially contribute to the decreased lethality of the multiple-site mutant.
Charge reversal of ammodytoxin A, a phospholipase A2-toxin, does not abolish its neurotoxicity
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Petra PRIJATELJ, Alenka ČOPIČ, Igor KRIŽAJ, Franc GUBENŠEK, Jože PUNGERČAR; Charge reversal of ammodytoxin A, a phospholipase A2-toxin, does not abolish its neurotoxicity. Biochem J 1 December 2000; 352 (2): 251–255. doi: https://doi.org/10.1042/bj3520251
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