Transformation of a non-enzymatic toxin into a toxoid by genetic engineering.
Protein Eng
; 10(10): 1213-20, 1997 Oct.
Article
em En
| MEDLINE
| ID: mdl-9488146
ABSTRACT
Curaremimetic toxins are typical non-enzymatic toxins that bind to their target [the nicotinic acetylcholine receptor (AChR)] through multiple residues. Nevertheless, we show that the concomitant substitutions of only three of the ten functionally important residues of such a toxin sufficed to cause an affinity decrease of the toxin for AChR that is higher than four orders of magnitude. Despite these triple mutations, the overall conformation of the mutated protein remains similar to that of a related recombinant toxin, as judged from both circular dichroism analysis and investigation of antigenicity, using monoclonal and polyclonal antibodies. Furthermore, we show that the detoxified toxin is capable of eliciting antibodies that neutralize the binding of a wild-type toxin to AChR. Therefore, transformation of a non-enzymatic toxin into a toxoid can be achieved, like in the case of enzymatic toxins, by introducing a small number of mutations at positions identified to be critical for expression of toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxoides
/
Mutagênese Sítio-Dirigida
/
Receptores Nicotínicos
/
Erabutoxinas
Limite:
Animals
Idioma:
En
Revista:
Protein Eng
Assunto da revista:
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
França