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Diphtheria Toxin and Pseudomonas aeruginosa Exotoxin A: Active-Site Structure and Enzymic Mechanism

  • Chapter
ADP-Ribosylating Toxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 175))

Abstract

Diphtheria toxin (DT), secreted by lysogenic strains of Corynebacterium diphtheriae carrying the phage-encoded DT gene, was the first ADP-ribosylating toxin for which the molecular mechanism of action was elucidated (Collier 1975; Pappenheimer 1977), and for many years DT has served as an important model system for studying the pathogenesis of bacterial exotoxins (Collier 1982; Jacobson and Jacobson 1989; Moss and Vaughan 1990). DT and the closely related exotoxin A from Pseudomonas aeruginosa(ETA) both catalyze the ADP-ribosylation of a post-translationally modified histidine (diphthamide) on elongation factor 2 (EF-2) (Honjo et al. 1968, 1969; Gill et al. 1969; Iglewski and Kabat 1975; Iglewski et al. 1977). EF-2 is a GTP-binding protein involved in protein biosynthesis by eukaryotic cells. ADP-ribosylated EF-2 is no longer able to mediate polypeptide chain elongation, and consequently, toxin-treated cells lose the ability to synthesize protein and ultimately die. Although toxins have not yet been described in detail, recent studies have yielded relevant information. This chapter will focus on some of the more recent studies and what the findings tell us about the structure of the active site and’the nature of the reaction catalyzed by these toxins.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, Harvard Medical School and Shipley Institute of Medicine, 260 Longwood Avenue, 02115, Boston, MA, USA

    B. A. Wilson & R. J. Collier

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  1. B. A. Wilson
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  2. R. J. Collier
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Editors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität des Saarlands, 6650, Homburg/saar, Germany

    Klaus Aktories

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© 1992 Springer-Verlag Berlin · Heidelberg

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Wilson, B.A., Collier, R.J. (1992). Diphtheria Toxin and Pseudomonas aeruginosa Exotoxin A: Active-Site Structure and Enzymic Mechanism. In: Aktories, K. (eds) ADP-Ribosylating Toxins. Current Topics in Microbiology and Immunology, vol 175. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76966-5_2

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  • DOI: https://doi.org/10.1007/978-3-642-76966-5_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76968-9

  • Online ISBN: 978-3-642-76966-5

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