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The Structure and Classification of Botulinum Toxins

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Botulinum Toxin Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 263))

Abstract

Botulinum neurotoxins (BoNTs) are a family of bacterial protein toxins produced by various Clostridium species. They are traditionally classified into seven major serotypes (BoNT/A-G). Recent progress in sequencing microbial genomes has led to an ever-growing number of subtypes, chimeric toxins, BoNT-like toxins, and remotely related BoNT homologs, constituting an expanding BoNT superfamily. Recent structural studies of BoNTs, BoNT progenitor toxin complexes, tetanus neurotoxin (TeNT), toxin-receptor complexes, and toxin-substrate complexes have provided mechanistic understandings of toxin functions and the molecular basis for their variations. The growing BoNT superfamily of toxins present a natural repertoire that can be explored to develop novel therapeutic toxins, and the structural understanding of their variations provides a knowledge basis for engineering toxins to improve therapeutic efficacy and expand their clinical applications.

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Acknowledgments

We thank Jonathan Davies for preparing all figures and for valuable discussions during the preparation of this chapter. This work was supported by the Swedish Research Council and the Swedish Cancer Society to P.S. and by grants from NIH (R01NS080833, R01AI132387, R01AI139087, and R21NS106159), Intelligence Advanced Research Projects Activity (IARPA, grant number W911NF-17-2-0089), and the Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund to M.D.

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Authors and Affiliations

  1. Department of Urology, Boston Children’s Hospital, Boston, MA, USA

    Min Dong

  2. Department of Microbiology, Harvard Medical School, Boston, MA, USA

    Min Dong

  3. Department of Surgery, Harvard Medical School, Boston, MA, USA

    Min Dong

  4. Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

    Pål Stenmark

  5. Department of Experimental Medical Science, Lund University, Lund, Sweden

    Pål Stenmark

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  1. Min Dong
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  2. Pål Stenmark
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Correspondence to Min Dong or Pål Stenmark .

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  1. Akrivista and Whitecap Biosciences, Irvine, CA, USA

    Scott M. Whitcup

  2. Bethesda, MD, USA

    Mark Hallett

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Dong, M., Stenmark, P. (2019). The Structure and Classification of Botulinum Toxins. In: Whitcup, S.M., Hallett, M. (eds) Botulinum Toxin Therapy. Handbook of Experimental Pharmacology, vol 263. Springer, Cham. https://doi.org/10.1007/164_2019_342

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