EC Number   |
General Information |
Reference |
|---|
   2.4.1.B62 | malfunction |
the deletion mutant TcdBD1756-1780 shows similar glucosyltransferase and cysteine protease activity, cellular binding, and pore formation to wild-type TcdB, but it fails to induce the glucosylation of Rho GTPase Rac1 of host cells. Moreover, TcdBD1756-1780 is rapidly degraded in the endosome of target cells, and therefore its intact glucosyltransferase domain is unable to translocate efficiently into host cytosol. The decrease in the alpha helical structure in the composition of TcdBD1756-1780 may be due to the deletion of AA 1756-1780. Domain structures of wild-type and mutant enzymes, overview. The deletion of region 1756-1780 might lead to locking of the TcdB in endosomes, resulting in a failure to deliver GTD |
760217 |
| 2.4.1.B62 | malfunction |
the difference in cellular Rac1 and Ras glucosylation when the autoprocessing activity is ablated (mutation C698A) suggests that there is a localization difference for Rac1 and Ras. Mutations in the GTD membrane localization domain inhibit TcsL cytotoxicity |
-, 759813 |
| 2.4.1.B62 | metabolism |
cytotoxin A possesses an inherent cysteine protease activity, which is responsible for auto-cleavage of glucosylating toxins |
727860 |
| 2.4.1.B62 | metabolism |
cytotoxin B possesses an inherent cysteine protease activity, which is responsible for auto-cleavage of glucosylating toxins |
727860 |
| 2.4.1.B62 | more |
the toxin requires InsP6-dependent autocleavage for activation |
760217 |
| 2.4.1.B62 | physiological function |
Clostridioides difficile toxin A (TcdA) and Toxin B (TcdB) trigger inflammasome activation with caspase-1 activation in cultured cells, which in turn induce the release of IL-6, IFN-g, and IL-8. Release of these proinflammatory responses is positively regulated by Ras-GTPases, which leads to the hypothesis that Ras glucosylation by glucosylating toxins results in (at least) reduced proinflammatory responses. Quantitative evaluation of the GTPase substrate profiles glucosylated in human colonic (Caco-2) cells treated with either TcdA, TcdB, or the related Clostridium sordellii lethal toxin (TcsL), performed by using multiple reaction monitoring (MRM) mass spectrometry. TcdA (not TcdB) glucosylates Ras subtype GTPases correlating with the fact that TcdB (not TcdA) is primarily responsible for inflammatory responses in Clostridioides difficile infection (CDI) |
-, 759247 |
| 2.4.1.B62 | physiological function |
full-length hemorrhagic toxin TcsH exclusively glucosylates Rho-GTPases. The recombinant transferase domain glucosylates preferably Rho-GTPases but also Ras-GTPases to some extent. Vero cells treated with full length TcsH also show glucosylation of Ras, albeit to a lower extent than of Rho-GTPases. In addition, enzyme induces a rapid dephosphorylation of pY118-paxillin and of pS144/141-PAK1/2 prior to actin filament depolymerization |
-, 735911 |
| 2.4.1.B62 | physiological function |
glucosylation of Ras by lethal toxin results in inhibition of the epidermal growth factor-stimulated p42/p44 MAP-kinase signal pathway |
-, 727817 |
| 2.4.1.B62 | physiological function |
in cell culture toxin A inhibits Clostridium botulinum ADP-ribosyltransferase C3-catalyzed ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Toxin A-induced decrease in ADP-ribosylation is observed also in cell lysates and with recombinant RhoA protein |
728038 |
| 2.4.1.B62 | physiological function |
isoform TcsL enters target cells via receptor-mediated endocytosis and delivers the N-terminal catalytic domain (TcsL-cat) into the cytosol. TcsL-cat binds to brain phosphatidylserine-containing membranes and to phosphatidic acid and, to a lesser extent, to other anionic lipids, but not to neutral lipids, sphingolipids or sterol. The lipid unsaturation status influences TcsL-cat binding to phospholipids, phosphatidylserines with unsaturated acyl chains and phosphatidic acids with saturated acyl chains being the preferred binding substrates. The phospholipid binding site is localized at the N-terminal four helical bundle structure (1-93 domain). Recombinant TcsL-1-93 binds to a broad range of substrates, whereas TcsL-cat, which is the active domain physiologically delivered into the cytosol, selectively binds to phosphatidylserine and phosphatidic acid |
735912 |
