GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:22267739
| Citation |
Pruitt, RN, Chumbler, NM, Rutherford, SA, Farrow, MA, Friedman, DB, Spiller, B and Lacy, DB (2012) Structural determinants of Clostridium difficile toxin A glucosyltransferase activity. J. Biol. Chem. 287:8013-20 |
|---|---|
| Abstract |
The principle virulence factors in Clostridium difficile pathogenesis are TcdA and TcdB, homologous glucosyltransferases capable of inactivating small GTPases within the host cell. We present crystal structures of the TcdA glucosyltransferase domain in the presence and absence of the co-substrate UDP-glucose. Although the enzymatic core is similar to that of TcdB, the proposed GTPase-binding surface differs significantly. We show that TcdA is comparable with TcdB in its modification of Rho family substrates and that, unlike TcdB, TcdA is also capable of modifying Rap family GTPases both in vitro and in cells. The glucosyltransferase activities of both toxins are reduced in the context of the holotoxin but can be restored with autoproteolytic activation and glucosyltransferase domain release. These studies highlight the importance of cellular activation in determining the array of substrates available to the toxins once delivered into the cell. |
| Links |
PubMed PMC3318759 Online version:10.1074/jbc.M111.298414 |
| Keywords |
Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Bacterial Toxins/chemistry; Bacterial Toxins/metabolism; Clostridium difficile/enzymology; Enterotoxins/chemistry; Enterotoxins/metabolism; Enzyme Activation/physiology; Glucosyltransferases/chemistry; Glucosyltransferases/metabolism; Protein Structure, Tertiary; Uridine Diphosphate Glucose/chemistry; Uridine Diphosphate Glucose/metabolism; rap GTP-Binding Proteins/chemistry; rap GTP-Binding Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0016757: transferase activity, transferring glycosyl groups |
ECO:0000314: |
F |
Figure 3 shows contrasting glycosylation activity of TcdA and TcdB for various GTPase's (RhoA, Rac1, Cdc42, Rap2A) |
complete | ||||
|
enables |
GO:0016757: transferase activity, transferring glycosyl groups |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
See Help:References for how to manage references in GONUTS.
