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Nontoxic, multi-domain botulinum neurotoxin-LCHC as vaccines against botulism.
Botulinum neurotoxins (BoNTs), the causative agents of botulism, are proteins consisting of an N-terminal catalytic Light Chain (LC) and a C-terminal Heavy Chain (HC), which comprises a LC-translocation domain (HC) and a receptor binding do…
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How Botulinum Neurotoxin Light Chain A1 Maintains Stable Association with the Intracellular Neuronal Plasma Membrane.
Botulinum neurotoxin serotype A (BoNT/A) is the most potent protein toxin for humans and is utilized as a therapy for numerous neurologic diseases. BoNT/A comprises a catalytic Light Chain (LC/A) and a Heavy Chain (HC/A) and includes eight …
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Resolving the Molecular Steps in Clostridial Neurotoxin Light Chain Translocation.
The clostridial neurotoxins (CNTs), botulinum toxin and tetanus toxin, are the most toxic proteins for humans. Neurotoxicity is based upon the specificity of the CNTs for neural host receptors and substrates. CNTs are organized into three d…
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The Light Chain Defines the Duration of Action of Botulinum Toxin Serotype A Subtypes.
Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa protein toxins organized into heavy chain (HC) and light chain (LC) domains linke…
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Entry of Botulinum Neurotoxin Subtypes A1 and A2 into Neurons.
Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans but also are common therapies for neurological diseases. BoNTs are dichain toxins, comprising an N-terminal catalytic domain (LC) disulfide bond linked to a C-terminal hea…
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Protein Structure Facilitates High-Resolution Immunological Mapping.
Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees vaccine and therapy development, and approves animal models and approaches t…