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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Journal ArticleDOI
Modulation of botulinum neurotoxin A catalytic domain stability by tyrosine phosphorylation.
Cristina Ibañez,Clara Blanes-Mira,Gregorio Fernández-Ballester,Rosa Planells-Cases,Antonio Ferrer-Montiel +4 more
TL;DR: Findings substantiate the tenet that tyrosine phosphorylation of BoNT A LC could be an important modulatory strategy of the neurotoxin stability and suggest that the phosphorylated neurotoxin may be a relevant molecule in vivo.
Book ChapterDOI
Uptake of Clostridial Neurotoxins into Cells and Dissemination.
Chloé Connan,Michel R. Popoff +1 more
TL;DR: BoNTs induce a flaccid paralysis (botulism) by inhibiting acetylcholine release at the neuromuscular junctions, whereas TeNT causes a spastic paralysis (tetanus) by blocking the neurotransmitter release in inhibitory interneurons within the central nervous system.
Journal ArticleDOI
Peptide inhibitors of botulinum neurotoxin by mRNA display.
TL;DR: A synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein is produced and a combinatorial peptide library is constructed to screen for Bo NT/A light chain inhibitors using mRNA display, suggesting that mRNA display may provide a general approach in developing peptide inhibitors of Bo NTs.
Journal ArticleDOI
Crystallization and preliminary X‐ray analysis of Clostridium botulinum neurotoxin type B
TL;DR: Native data have been collected from flash-frozen crystals at the National Synchrotron facility of Brookhaven National Laboratory, where these crystals often tend to be non-isomorphic.
Patent
Botulinum toxin A peptides and methods of predicting and reducing immunoresistance to botulinum toxin therapy
TL;DR: In this article, the authors presented a method of predicting or determining immunoresistance to botulinum toxin therapy in an individual using BoNT/A peptides, which was shown to be more effective than traditional methods.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
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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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