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
Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.
TL;DR: The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies, and suggest novel uses in therapeutics with increasing disease/symptom specifity.
Journal ArticleDOI
Botulinum neurotoxins: genetic, structural and mechanistic insights
TL;DR: This Review discusses recent studies that have improved the understanding of the genetics and structure of the BoNT complexes and describes recent insights into the mechanisms of BoNT entry into the general circulation, neuronal binding, membrane translocation and neuroparalysis.
Journal ArticleDOI
Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B.
TL;DR: The structures of BoNT/B and its complex with sialyllactose provide a detailed description of the active site and a model for interactions between the toxin and its cell surface receptor, and the latter may provide valuable information for recombinant vaccine development.
Journal ArticleDOI
European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity.
André Reitz,Manfred Stöhrer,G. Kramer,Giulio Del Popolo,Emmanuel Chartier-Kastler,Jürgen Pannek,H. Burgdörfer,Konrad Göcking,Helmut Madersbacher,S. Schumacher,Rudolf Richter,Jan von Tobel,Brigitte Schurch +12 more
TL;DR: This retrospective European multicenter study presents the most extensive experience to date with BTA injections into thedetrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new treatment is safe and valuable.
Journal ArticleDOI
Botulinum and tetanus neurotoxins: structure, function and therapeutic utility
TL;DR: The relationships between structure, mechanism of action and therapeutic use of botulinum neurotoxins are discussed.
References
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