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
Small-Molecule Quinolinol Inhibitor Identified Provides Protection against BoNT/A in Mice
Padma Singh,Manglesh Kumar Singh,Dilip Chaudhary,Vinita Chauhan,Pranay Bharadwaj,Apurva Pandey,Nisha Upadhyay,Ram Kumar Dhaked +7 more
TL;DR: NSC 84087 is the most potent inhibitor reported so far, found to be a promising lead for therapeutic development, as it exhibits no toxicity, and is able to protect animals from pre and post challenge of botulinum neurotoxin type A (BoNT/A).
Journal ArticleDOI
Understanding peptide competitive inhibition of botulinum neurotoxin A binding to SV2 protein via molecular dynamics simulations.
TL;DR: The structural stability analysis indicates that BoNT/A‐A2 system is more stable than SV2C‐A3 system and the internal hydrogen bonds play crucial roles in the structural stability of the peptides, which is helpful in understanding the inhibition mechanisms of peptide inhibitors.
Journal ArticleDOI
Immunoprecipitation of native botulinum neurotoxin complexes from Clostridium botulinum subtype A strains.
TL;DR: In this study, BoNT/A subtypes A1, A2, A3, and A5 were examined for the compositions of their TCs in culture extracts using immunoprecipitation (IP), and IP analyses showed that BoNT /A1 and Bo NT/A5 form TC1s, while BoNT and A3 form TC2s, which were more stable than TC2 complexes.
Journal ArticleDOI
Characterization of Clostridium butyricum neurotoxin associated with food-borne botulism.
Kentaro Tsukamoto,Masafumi Mukamoto,Tomoko Kohda,Hideshi Ihara,Xingmin Wang,Tsuneo Maegawa,Shinichi Nakamura,Tadahiro Karasawa,Shunji Kozaki +8 more
TL;DR: Investigation of the neurotoxin of Clostridium butyricum strain LCL155 associated with type E food-borne botulism suggests that it shares the receptor-recognition site structurally different from BoNT/E and BuNT/BL5262, perhaps causing a decreased specific toxicity.
Journal Article
Characterization of the monoclonal antibody response to botulinum neurotoxin type A in the complexed and uncomplexed forms.
TL;DR: Investigation of the different binding capabilities of the mAbs to BoNT and the complex toxin by immunoprecipitation suggested that the light chain of BoNT is exposed at the molecular surface of the complex toxins since there was no difference in the binding of light chain-specific mAb to Bo NT and thecomplex toxin.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Improved Fourier coefficients for maps using phases from partial structures with errors
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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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