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Proteolysis of synthetic peptides by type A botulinum neurotoxin

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Abstract

Type A botulinum neurotoxin catalyzed the hydrolysis of synthetic peptides based on the sequence of the 25-kD synaptosomal protein SNAP-25. In each peptide, the toxin cleaved at a single glutaminyl-arginine bond corresponding to residues 197 and 198 of SNAP-25, confirming earlier reports on the enzymatic specificity of the toxin in synaptosomal preparations. Metal chelators inhibited catalysis, consistent with a metalloprotease activity. In contrast to tetanus toxin and other botulinum toxin serotypes, type A toxin hydrolyzed relatively short, 17-to 20-residue peptides. In the substrates, SNAP-25 residue 202 and one or more of residues 187–191 were required for efficient hydrolysis, but residues 167–186 and 203–206 were not. The highest rates of hydrolysis were found when the C-terminal residues of the peptides were amidated.

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References

  • Blasi, J., Chapman, E. R., Link, E., Binz, T., Yamasaki, S., De Camilli, P., Sudhof, T. C., Nieman, H., and Jahn, R. (1993).Nature 365, 160–163.

    Article  CAS  PubMed  Google Scholar 

  • Cornille, F., Goudreau, N., Ficheux, D., Nieman, H., and Roques, B. (1994).Eur. J. Biochem. 222, 173–181.

    Article  CAS  PubMed  Google Scholar 

  • Dolly, J. O. (1992). In:Handbook of Experimental Pharmacology (Herken, H., and Hucho, F., eds.), Springer-Verlag, Berlin, pp. 681–717.

    Google Scholar 

  • Eipper, B. A., and Mains, R. E. (1988).Annu. Rev. Physiol. 50, 333–344.

    Article  CAS  PubMed  Google Scholar 

  • Eisel, U., Jarausch, W., Goretzki, K., Henschen, A., Engels, J., Weller, U., Hudel, M., Habermann, E., and Nieman, H. (1986).EMBO J. 5, 2495–2502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foran, P., Shone, C. C., and Dolly, J. O. (1994).Biochemistry 33, 15365–15374.

    Article  CAS  PubMed  Google Scholar 

  • Hansen, S., Kristian, L., and Hough, E. (1993).J. Mol. Biol. 231, 870–876.

    Article  CAS  PubMed  Google Scholar 

  • Jankovic, J., and Brin, M. F. (1992).N. Engt J. Med. 324, 1186–1194.

    Google Scholar 

  • Jongeneel, C. V., Bouvier, J., and Bairoch, A. (1989).FEBS Lett. 242, 211–214.

    Article  CAS  PubMed  Google Scholar 

  • Nieman, H. (1991). InSourcebook of Bacterial Protein Toxins (Alouf, J., and Freer, J., eds.), Academic Press, New York, pp. 303–348.

    Google Scholar 

  • Nieman, H., Blasi, J., and Jahn, R. (1994).Trends Cell Biol. 4, 179–185.

    Article  Google Scholar 

  • Oyler, G. A., Higgins, G. A., Hart, R. A., Battenberg, E., Billingsley, M., Bloom, F. E., and Wilson, M. C. (1989).J. Cell Biol. 109, 3039–3052.

    Article  CAS  PubMed  Google Scholar 

  • Rosetto, O., Schiavo, G., Montecucco, C., Poulain, B., Deloye, F., Lozzi, L., and Shone, C. C. (1994).Nature 372, 415–416.

    Article  Google Scholar 

  • Schiavo, G., Benfenatti, F., Poulain, B., Rossetto, O., deLaureto, P. P., DasGupta, B. R., and Montecucco, C. (1992a).Nature 359, 832–835.

    Article  CAS  PubMed  Google Scholar 

  • Schiavo, G., Poulain, B., Rossetto, O., Benfenatti, F., Tauc, L., and Montecucco, C. (1992b).EMBO J. 11, 3577–3583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schiavo, G., Rossetto, O., Catsicas, S., de Laureto, P. P., DasGupta, B. R., Benfenati, F., and Montecucco, C. (1993).J. Biol. Chem. 268, 23784–23787.

    Article  CAS  PubMed  Google Scholar 

  • Schiavo, G., Rossetto, O., and Montecucco, C. (1994).Cell Biol. 5, 221–229.

    CAS  Google Scholar 

  • Shone, C. C., and Roberts, A. K. (1994).Eur. J. Biochem. 225, 263–270.

    Article  CAS  PubMed  Google Scholar 

  • Shone, C. C., Quinn, C. P., Wait, R., Hallis, B., Fooks, S., and Hambleton, P. (1993).Eur. J. Biochem. 217, 965–971.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, L. L. (1981).Pharmacol. Rev. 33, 155–188.

    CAS  PubMed  Google Scholar 

  • Simpson, L. L. (1984).J. Pharmacol. Exp. Ther. 230, 665–669.

    CAS  PubMed  Google Scholar 

  • Yamasaki, S., Baumeister, A., Binz, T., Blasi, J., Link, E., Cornille, F., Rocques, B., Fykse, E. M., Sudhof, T. C., Jahn, R., and Nieman, H. (1994).J. Biol. Chem. 269, 12764–12772.

    Article  CAS  PubMed  Google Scholar 

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Schmidt, J.J., Bostian, K.A. Proteolysis of synthetic peptides by type A botulinum neurotoxin. J Protein Chem 14, 703–708 (1995). https://doi.org/10.1007/BF01886909

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  • DOI: https://doi.org/10.1007/BF01886909

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