Molecular differences between type A botulinum neurotoxin and its toxoid
1989; Elsevier BV; Volume: 27; Issue: 4 Linguagem: Inglês
10.1016/0041-0101(89)90202-x
ISSN1879-3150
AutoresBal Ram Singh, Bibhuti R. DasGupta,
Tópico(s)Neurological disorders and treatments
ResumoB. R. Singh and B. R. DasGupta. Molecular differences between bype A botulinum neurotoxin and its toxoid. Toxicon27, 403–410, 1989.—The neurotoxins (seven serotypes, Mr ∼ 150,000) produced by Clostridium botulinum cause the neuroparalytic disease botulism. Prophylaxis, definitive diagnosis and the only effective therapy for botulism depend, at present, on chemically detoxified form(s) of the neurotoxins, i.e. toxoids (immunogens), and the antisera raised with the immunogens. And yet, the toxoids currently used for immunization of humans and animals and for raising antibody are very crude preparations (∼90% impure) of the neurotoxins. Hence, the highly heterogenous toxoids were not suitable for physicochemical studies. We have detoxified a pure (>99%) neurotoxin (serotype A) with formaldehyde. The native neurotoxin is composed of two subunit chains (Mr 53,000 and 97,000). The physicochemical properties of the toxoid (immunogenic in rabbits) were analyzed. The chemical modification produced inter- and intrasubunit covalent links at multiple sites and thus extensive aggregation of the neurotoxin. The secondary structure parameters (α-helix, β-sheet, β-turn and random coil) of the native protein were not significantly altered. Tertiary structure, as measured by exposure of tyrosine residues and fluorescence quantum yield of tryptophan residues, was considerably altered. The data imply that conformational (topographical) antigenic determinants may not contribute significantly to the serological property of the neurotoxin.
Referência(s)