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
The Crystal Structure of Tetanus Toxin Hc Fragment Complexed with a Synthetic GT1b Analogue Suggests Cross-linking between Ganglioside Receptors and the Toxin
Constantina Fotinou,Paul Emsley,Isobel Black,Hiromune Ando,Hideharu Ishida,Makoto Kiso,Katharine Sinha,Neil F. Fairweather,Neil W. Isaacs +8 more
TL;DR: The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the gangliosiside-binding sites.
Journal ArticleDOI
Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective.
Eric A. Johnson,Marite Bradshaw +1 more
TL;DR: Evidence suggests that negative regulatory factors and general control cascades such as those involved in nitrogen regulation and carbon catabolite repression also regulate synthesis of BoNTs, which have the common property of producing a distinctive protein neurotoxin of similar pharmacological activity and extraordinary potency.
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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
TL;DR: A strategic plan for preparedness and response to biological and chemical terrorism and its impact on health and safety is recommended by the CDC Strategic Planning Workgroup.
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Bacterial protease inhibitors
TL;DR: The state of the art in the design of such enzyme inhibitors with potential therapeutic applications, as well as recent advances in the use of some of these proteases in therapy are presented.
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Enzyme family classification by support vector machines.
TL;DR: Testing results suggest that SVM in some cases is capable of classification of distantly related enzymes and homologous enzymes of different functions, and the potential of SVM for enzyme family classification and for facilitating protein function prediction is suggested.
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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