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Glucosyltransferase Domain of Clostridioides difficile Toxins (GTD)
- Target
- GTD
- Molecular classification
- Enzyme, Glucosyltransferase
01
Overview
The glucosyltransferase domain (GTD) is the N-terminal catalytic region of Clostridioides difficile toxins A (TcdA) and B (TcdB). It functions as a glucosyltransferase, modifying and inactivating Rho-family GTPases within host cells. This inactivation disrupts the actin cytoskeleton, leading to cell rounding, loss of epithelial barrier function, inflammation, and ultimately cell death. The GTD is essential for the cytotoxic activity of these toxins and is an attractive target for therapeutic intervention against C. difficile infections.
- Other names
- TcdA Glucosyltransferase DomainTcdB Glucosyltransferase DomainClostridioides difficile Toxin A Glucosyltransferase DomainClostridioides difficile Toxin B Glucosyltransferase Domain
02
Mechanism of action
Inhibition of glucosyltransferase activity, preventing glucosylation and inactivation of Rho GTPases
03
Biological functions
Glucosylation of Rho GTPasesInactivation of Rho GTPasesDisruption of actin cytoskeletonCell roundingLoss of epithelial barrier function
04
Disease associations
Clostridioides difficile infectionPseudomembranous colitisDiarrheaColitisInflammation
05
Safety considerations
Specificity for bacterial GTD over host GTDs is crucial to minimize off-target effectsPotential for resistance development if inhibitors target the catalytic site
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