Molecular Topography and Secondary Structure Comparisons of Botulinum Neurotoxin Types A, B and E
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Botulinum neurotoxin (NT) serotypes A, B and E differ in microstructure and biological activities. The three NTs were examined for secondary structure parameters (alpha-helix, beta-sheet, beta-turn and random coil content) on the basis of circular dichroism; degree of exposed Tyr residues (second derivative spectroscopy) and state of the Trp residues (fluorescence and fluorescence quantum yield). The proteins are high in beta-pleated sheet content (41-44%) and low in alpha-helical content (21-28%). About 30-36% of the amino acids are in random coils. The beta-sheet contents in the NTs are similar irrespective of their structural forms (i.e. single or dichain forms) or level of toxicity. About 84%, 58% and 61% of Tyr residues of types A, B, and E NT, respectively, were exposed to the solvent (pH 7.2 phosphate buffer). Although the fluorescence emission maximum of Trp residues of type B NT was most blue shifted (331 nm compared to 334 for types A and E NT, and 346 nm for free tryptophan) the fluorescence quantum yields of types A and B were similar and higher than type E. In general the NTs have similar secondary (low alpha-helix and high beta-sheets) and tertiary (exposed tyrosine residues and tryptophan fluorescence quantum yield) structures. Within this generalized picture there are significant differences which might be related to the differences in their biological activities.
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Singh B Neurotox Res. 2006; 9(2-3):73-92.
PMID: 16785103 DOI: 10.1007/BF03033925.
Singh B, Wasacz F, Strand S, Jakobsen R, Dasgupta B J Protein Chem. 1990; 9(6):705-13.
PMID: 2073322 DOI: 10.1007/BF01024765.
Singh B, Fuller M, Dasgupta B J Protein Chem. 1991; 10(6):637-49.
PMID: 1815589 DOI: 10.1007/BF01025716.