Journal ArticleDOI
Crystal structure of botulinum neurotoxin type A and implications for toxicity.
TLDR
The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined and the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.Abstract:
Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a potential biological weapon and an effective therapeutic drug for involuntary muscle disorders. The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined at 3.3 A resolution. The structure reveals that the translocation domain contains a central pair of alpha-helices 105 A long and a approximately 50 residue loop or belt that wraps around the catalytic domain. This belt partially occludes a large channel leading to a buried, negative active site--a feature that calls for radically different inhibitor design strategies from those currently used. The fold of the translocation domain suggests a mechanism of pore formation different from other toxins. Lastly, the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.read more
Citations
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Insights into the Mechanisms by Which Clostridial Neurotoxins Discriminate between Gangliosides.
TL;DR: It is demonstrated that targeted mutations within the Sia5 binding pocket result in the generation of neurotoxins that either bind and enter cells more efficiently (BoNT/A1 and BoNT/B) or display altered ganglioside binding specificity (TeNT).
Journal ArticleDOI
A novel role of C-terminus in introducing a functionally flexible structure critical for the biological activity of botulinum neurotoxin.
TL;DR: It is reported that the fLCA structure is significantly more flexible than tLCA in solution, which may be responsible for its dramatically higher enzymatic activity and the first report of such a massive structural role of the C-terminus of a protein being critical for maintaining a functional state.
Botulinum Toxin as a Biological WeaponMedical and Public Health Management
TL;DR: Arnon et al. as mentioned in this paper presented a report for the Working Group on Civilian Biodefense (WGBIF) for the first time, where they discussed the role of women in the field of bio-medical research.
Journal ArticleDOI
BotDB: A database resource for the clostridial neurotoxins.
TL;DR: BotDB is a database designed to encapsulate the rapidly expanding amount of information about the structure and function of the botulinum and tetanus neurotoxins and to track a variety of basic and applied research efforts.
References
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Improved Fourier coefficients for maps using phases from partial structures with errors
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Journal ArticleDOI
Atomic structure of the ectodomain from HIV-1 gp41
Winfried Weissenhorn,Andréa Dessen,Stephen C. Harrison,Stephen C. Harrison,John J. Skehel,Don C. Wiley,Don C. Wiley +6 more
TL;DR: X-ray crystallography determines the structure of the protease-resistant part of a gp41 ectodomain solubilized with a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide, and suggests a common mechanism for initiating fusion.
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Botulinum Toxin as a Biological Weapon: Medical and Public Health Management
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