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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Book ChapterDOI
Botulinum Toxin in Chronic Pelvic Pain Management
TL;DR: There is the urgent need to have adequate randomized, controlled studies to definitively establish the role of botulinum toxins in treating pelvic pain conditions.
Book ChapterDOI
Overview and History of Botulinum Neurotoxin Research
TL;DR: Establishing the structural basis of neurotoxin activity has further increased understanding of neurot toxin function together with opening up opportunities to engineer the toxins to create proteins of increased therapeutic effect and potential.
Journal ArticleDOI
Pathogenicity and virulence of Clostridium botulinum
TL;DR: Botulinum neurotoxin (BoNT) is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis as discussed by the authors .
Journal ArticleDOI
Serotype Features of 17 Suspected Cases of Foodborne Botulism in China 2019–2022 Revealed by a Multiplex Immuno-Endopep-MS Method
TL;DR: A feasible laboratorial method based on an isotope dilution Immuno-Endopep-MS to detect BoNTs and determine their serotypes and activities in clinical samples is developed, providing the first comprehensive analytical research on in vivo profiles of serotypes A, B, and E in different types of specimens from mixed botulism cases.
Book ChapterDOI
Molecular Structure and Mechanisms of Action of Botulinum Neurotoxins
Ornella Rossetto,Marco Pirazzini +1 more
TL;DR: In this article, the authors report the progress on their understanding of BoNTs, highlighting the different steps of their molecular mechanism of action as key aspects to explain their extreme toxicity but also their unique pharmacological properties.
References
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Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
Improved methods for building protein models in electron density maps and the location of errors in these models.
TL;DR: In this paper, the authors describe strategies and tools that help to alleviate this problem and simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
Journal ArticleDOI
Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.
TL;DR: It is demonstrated in this work that the surface tension, water‐organic solvent, transfer‐free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions.
Journal ArticleDOI
Improved Fourier coefficients for maps using phases from partial structures with errors
TL;DR: In this article, a method is given to estimate the parameter σA in these phase probability expressions from the observed and calculated structure factor amplitudes, from which one can estimate the mean coordinate error for the model, and when there are coordinate errors, a new expression for the non-centric Fourier coefficients is required to suppress this model bias.
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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