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
Zinc-mediated Dimerization and Its Effect on Activity and Conformation of Staphylococcal Enterotoxin Type C
Young In Chi,Ingrid Sadler,Lynn M. Jablonski,Scott D. Callantine,Claudia F. Deobald,Cynthia V. Stauffacher,Gregory A. Bohach +6 more
TL;DR: Investigation of the potential importance of zinc in SEC-mediated pathogenesis found that site-directed mutagenesis was used to replace SEC zinc binding ligands with alanine, and mutants unable to bind zinc did not have major conformational alterations although they failed to form dimers.
Journal ArticleDOI
Interaction of botulinum toxin with the epithelial barrier.
TL;DR: An overview of the structural features of botulinum toxins (BoNT and BoNT complex) and the interaction of these toxins with the epithelial barrier is provided.
Journal ArticleDOI
Tyrosine-1290 of tetanus neurotoxin plays a key role in its binding to gangliosides and functional binding to neurones.
TL;DR: Using site‐directed mutagenesis, tyrosine‐1290 of tetanus toxin is identified as a key residue that is involved in ganglioside binding and shown to play a key role in the functional binding of Tetanus toxin to spinal cord neurones leading to the inhibition of neurotransmitter release.
Journal ArticleDOI
Military Importance of Natural Toxins and Their Analogs.
Vladimír Pitschmann,Zdeněk Hon +1 more
TL;DR: The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents and appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.
Journal ArticleDOI
Medical aspects of biologic toxins.
TL;DR: This article focuses on the botulinum neurotoxins, because these are the most poisonous substances known and are the only toxins classified as Category A threat agents-the highest level of threat agent.
References
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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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