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
Neuronal selectivity of botulinum neurotoxins
TL;DR: A literature review of the neuronal selectivity of BoNTs is reported, finding that in in vivo models, BoNT/A impairs the cholinergic neuronal transmission at the motor-neurons but also at neurons controlling secretions and smooth muscle neurons, and blocks several neuronal pathways including excitatory, inhibitory, and sensitive neurons.
Journal ArticleDOI
Stability of botulinum neurotoxin type A, devoid of complexing proteins
TL;DR: NT201 was found to be stable without refrigeration for 48 months and even not affected by short-term temperature stress up to 60°C, demonstrating that complexing proteins are not required for the stability of BoNT/A preparations.
Patent
Pegylated mutated clostridium botulinum toxin
Juergen Frevert,Specht Volker +1 more
TL;DR: In this paper, a modified botulinum toxin which has a naturally occurring heavy chain and a modified light chain was described, where the modification of the light chain is characterized in that it comprises (i) on its N terminus an extension of the chain which has the structure -(C)n-(tag)m-(X)l- in the direction from the n terminus to the C terminus, C representing a cysteine group, tag representing any tag and X representing a group of any naturally occurring amino acid, n being an integer from 1 to 50
Book ChapterDOI
CD4+ T cells specific for factor VIII as a target for specific suppression of inhibitor production.
Mark T. Reding,Huiyun Wut,Mark Krampft,David K. Okita,Brenda Diethelm-Okita,Nigel S. Key,Bianca M. Conti-Fine +6 more
TL;DR: The murine hemophilia model will hopefully provide further insights into the mechanisms of inhibitor formation, and prove to be a suitable tool for the design and testing of therapeutic strategies aimed at preventing the development of fVIII inhibitors.
Journal ArticleDOI
Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule.
TL;DR: The human Ab recognition of the entire BoNT/B molecule is presented and compared to the recognition of BoNT-A by human blocking Abs and the remaining peptides had little or no Ab-binding activity.
References
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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
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Related Papers (5)
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