ArticleNature communications2017
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Evolution of botulinum neurotoxin serotype X proteases to induce inflammatory cell death in cancer cells.Nature biotechnology · 2026Article
- Cryo-EM Structure Guided Engineering of Botulinum Neurotoxin A With Advanced Receptor Binding Affinity and Therapeutical Benefits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of Microbial Toxins in Neurodegenerative Diseases: Insights and Future Perspectives.Biomolecules · 2026Review
- Advances in Clostridial Neurotoxins: Passage of the Intestinal Barrier and Targeting of Specific Neuronal Cells.Toxins · 2026Review
- Advances in the labelling and selective manipulation of synapses.Nature reviews. Neuroscience · 2024Review
- Pathogenicity and virulence ofVirulence · 2023Review
- Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2.Nature communications · 2023Article
- Article
- Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.Archives of toxicology · 2022Review
- Comparative transcriptomic analysis provides insights into transcription mechanisms of Vibrio parahaemolyticus T3SS during interaction with HeLa cells.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Article
- Article
- Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy.Toxins · 2021Review
- Knockin mouse models demonstrate differential contributions of synaptotagmin-1 and -2 as receptors for botulinum neurotoxins.PLoS pathogens · 2021Article
- Emerging Opportunities in Human Pluripotent Stem-Cells Based Assays to Explore the Diversity of Botulinum Neurotoxins as Future Therapeutics.International journal of molecular sciences · 2021Review
- Bioengineering ofToxins · 2021Review
- Review
- Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021Review
- The Structure and Classification of Botulinum Toxins.Handbook of experimental pharmacology · 2021Article
- The Use of Botulinum Toxin for Treatment of Spasticity.Handbook of experimental pharmacology · 2021Article
- Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development.Toxins · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 6 countries.
Funding
Abstract
Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B's therapeutic efficacy and reduce adverse effects. Here we utilized the bacterial adenylate cyclase two-hybrid method and carried out a saturation mutagenesis screen in the Syt II-binding pocket of botulinum neurotoxin B. The screen identifies E1191 as a key residue: replacing it with M/C/V/Q enhances botulinum neurotoxin B binding to human synaptotagmin II. Adding S1199Y/W or W1178Q as a secondary mutation further increases binding affinity. Mutant botulinum neurotoxin B containing E1191M/S1199Y exhibits ~11-fold higher efficacy in blocking neurotransmission than wild-type botulinum neurotoxin B in neurons expressing human synaptotagmin II, demonstrating that enhancing receptor binding increases the overall efficacy at functional levels. The engineered botulinum neurotoxin B provides a platform to develop therapeutic toxins with improved efficacy.Humans are less sensitive to the therapeutic effects of botulinum neurotoxin B (BoNT/B) than the animal models it is tested on due to differences between the human and the mouse receptors. Here, the authors engineer BoNT/B to improve its affinity to human receptors and enhance its therapeutic efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.