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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Patent
Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity
Dudley J. Williams,Marcella A. Gilmore,Lance E. Steward,Marc Verhagen,Kei Roger Aoki,Ester Fernandez-Salas +5 more
TL;DR: Clostridial toxin recognition sequence including a cleavage site was described in this article, and methods for determining the activity of a Clostridia toxin from a test sample using such Clostrian toxin substrates were presented.
Journal ArticleDOI
Botulinum neurotoxins: perspective on their existence and as polyproteins harboring viral proteases.
TL;DR: Assessment of the literature provided rationale to propose a consideration of the NT as a polyprotein harboring viral protease (the 50-kDa light chain) and to provide a perspective on the evolution of theNT into the present state where 8 NTs (botulinum plus tetanus) cleave 3 neuronal and 1 non-neuronal proteins at 7 sites.
Journal ArticleDOI
Partial protection against Botulinum B neurotoxin-induced blocking of exocytosis by a potent inhibitor of its metallopeptidase activity.
Christine Anne,Serge Turcaud,Armand G. S. Blommaert,François Darchen,Eric A. Johnson,Bernard P. Roques +5 more
TL;DR: Two of the first compounds to inhibit enzymatic activity of Clostridium botulinum neurotoxins prevent the BoNT/B‐induced cleavage of native synaptobrevin on synaptic vesicles, and partially inhibit the suppression of [3H]noradrenaline release from synaptosomes that is caused by Bo NT/B.
Journal ArticleDOI
The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins
TL;DR: The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism, and the kinetics of the Zn-dependent proteolytic activities of these neurotoxin activities are reviewed.
Book ChapterDOI
CHAPTER 19 – Attack of the nervous system by clostridial toxins: physical findings, cellular and molecular actions
TL;DR: This chapter summarizes the known pathophysiological and molecular actions on nerve terminals and nerve tissue of several potent toxins produced by Clostridium species, which includes the botulinum and tetanus neurotoxins, which are to date the best documented toxins acting on neurotransmitter release.
References
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Journal ArticleDOI
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Related Papers (5)
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