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 Light Chain Domain and Especially the C-Terminus of Receptor-Binding Domain of the Botulinum Neurotoxin (BoNT) Are the Hotspots for Amino Acid Variability and Toxin Type Diversity
TL;DR: An extensive analysis of all of the available 143 unique BoNT-encoding genes and their products found that most of the differences were concentrated along the protein’s light chain (LC) domain and especially, the C-terminus of the receptor-binding domain (HCC), identified as the main source of the toxin type differentiation.
Dissertation
Molecular basis for the therapeutic uses of botulinum neurotoxin for arthritic pain
TL;DR: This chapter discusses arthritis disease progression, treatment options, and current and future options for treatment.
Journal Article
Metal ion-mediated inactivation and small molecule inhibition of the metalloprotease in botulinum neurotoxin a
Abnormal somatosensory activation patterns in orofacial dystonia and their modulation by botulinum toxin examined by a fully automated tactile stimulation device in fMRI
TL;DR: Functional magnetic resonance imaging was used to explore abnormal central sensory processing of tactile stimuli applied by a fully automated stimulation device to the forehead, upper lips and hands before and after treatment with botulinum toxin (BTX) in patients with Blepharospasm or Meige's syndrome, finding BTX seems to modulate subcortical sensory processing.
Journal ArticleDOI
How Botulinum Neurotoxin Light Chain A1 Maintains Stable Association with the Intracellular Neuronal Plasma Membrane
TL;DR: In this paper , steady-state and live-imaging of a cytosolic LC/A3 derivative (LC/A 3V) engineered to contain individual structural elements of the A1 LDH showed that a 59 amino acid region (275−334) termed the MLD was sufficient to direct LC/ A3V from the cytosol to the plasma membrane co-localized with SNAP-25.
References
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Journal ArticleDOI
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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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