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Inhibition of the glucosyltransferase activity of clostridial Rho/Ras‐glucosylating toxins by castanospermine
Author(s) -
Jank Thomas,
Ziegler Mathias O.P.,
Schulz Georg E.,
Aktories Klaus
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.05.025
Subject(s) - castanospermine , glucosyltransferase , chemistry , clostridium difficile toxin a , toxin , moiety , clostridium , stereochemistry , clostridium difficile toxin b , biochemistry , biology , clostridium difficile , enzyme , bacteria , antibiotics , genetics
Castanospermine was identified as an inhibitor of the Rho/Ras‐glucosylating Clostridium sordellii lethal toxin and Clostridium difficile toxin B. Microinjection of castanospermine into embryonic bovine lung cells prevented the cytotoxic effects of toxins. The crystal structure of the glucosyltransferase domain of C. sordellii lethal toxin in complex with castanospermine, UDP and a calcium ion was solved at a resolution of 2.3 Å. The inhibitor binds in a conformation that brings its four hydroxyl groups and its N‐atom almost exactly in the positions of the four hydroxyls and of the ring oxygen of the glucosyl moiety of UDP–glucose, respectively.