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
Construction and validation of safe Clostridium botulinum Group II surrogate strain producing inactive botulinum neurotoxin type E toxoid
Maria B. Nowakowska,Katja Selby,Adina Przykopanski,Maren Krüger,Nadja Krez,Brigitte G. Dorner,Martin B. Dorner,Rongsheng Jin,Nigel P. Minton,Andreas Rummel,Miia Lindström +10 more
TL;DR: In this paper , the authors exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga Ei.
Journal ArticleDOI
Mechanism of substrate recognition by the novel Botulinum Neurotoxin subtype F5
TL;DR: The present study addressed for the first time the unique substrate recognition mechanism of LC/F5 and indicated that the optimal peptide required for efficient LC/f5 substrate cleavage is VAMP-2.
Journal Article
Inhibition of catalytic activities of botulinum neurotoxin light chains of serotypes A, B and E by acetate, sulfate and calcium
TL;DR: The results suggest that acetate, sulfate, and calcium nonspecifically interact with BoNT Lc, and their occurrence in the crystal structures could have been due to opportunistic binding to complementary pockets.
Patent
Small molecules and a pharmacophore model for inhibition of botulinum toxin and methods of making and using thereof
TL;DR: In this paper, a pharmacophore model for inhibiting Botulinum neurotoxin A metalloprotease activity is presented, which consists of a first plane A, a second plane B, a first hydrophobic moiety C, another hydrophilic moiety D and a positive ionizable substituent E.
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
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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