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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Posted ContentDOI
BAcTrace a new tool for retrograde tracing of neuronal circuits
Sebastian Cachero,Marina Gkantia,Alexander Shakeel Bates,Shahar Frechter,Laura Blackie,Laura Blackie,Amy McCarthy,Amy McCarthy,Ben Sutcliffe,Alessio Strano,Alessio Strano,Yoshinori Aso,Gregory S.X.E. Jefferis +12 more
TL;DR: BAcTrace (Botulinum Activated Tracer) is presented, the first fully genetically encoded, retrograde, transsynaptic labelling system based on C. botulinum neurotoxin A, Botox, engineered to act as a Trojan horse that jumps retrogradely between neurons to activate an otherwise silent transcription factor.
Dissertation
Expression of the botulinum neurotoxin serotype D binding domain in Brevibacillus brevis and its evaluation as a candidate vaccine antigen in mice
TL;DR: It could be concluded that the recombinant BoNT/D-SA(HC) protein is an effective immunogen, able to protect against a high challenge dose of BoNT /D-50 neurotoxin.
Book ChapterDOI
55 – Clostridium botulinum and associated neurotoxins
John A. Chaddock,Jack Melling +1 more
TL;DR: Clostridium botulinum is a rod-shaped, Gram positive, sporulating, anaerobic bacillus that is widely distributed in the environment that is restricted to environments of sufficiently low oxygen tension and enough quantities of organic material to permit survival and growth.
Book ChapterDOI
Medical Defense Against Protein Toxin Weapons
TL;DR: Technological changes have increased the importance of protein toxins for biological warfare (BW), and gene manipulation and microbiology have greatly expanded the accessible delivery vehicles for protein toxins to include, for example, natural or genetically modified bacteria and engineered viruses.
Book ChapterDOI
Future Developments: Engineering the Neurotoxin
TL;DR: This chapter brings together the findings detailed in the companion volume to this book, KA Foster (ed) Molecular Aspects of Bo- tulinum Neurotoxin, Springer, New York, and shows how they can be applied for the development of innovative therapeutics and research tools.
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.
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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.
Related Papers (5)
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Stephen S. Arnon,Robert Schechter,Thomas V. Inglesby,Donald A. Henderson,John G. Bartlett,Michael S. Ascher,Edward M. Eitzen,Anne D. Fine,Jerome Hauer,Marcelle Layton,Scott R. Lillibridge,Michael T. Osterholm,Tara O'Toole,Gerald W. Parker,Trish M. Perl,Philip K. Russell,David L. Swerdlow,Kevin Tonat +17 more