3srz

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Clostridium difficile toxin A (TcdA) glucolsyltransferase domain bound to UDP-glucoseClostridium difficile toxin A (TcdA) glucolsyltransferase domain bound to UDP-glucose

Structural highlights

3srz is a 1 chain structure with sequence from Clod6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Gene:CD0663, CD630_06630, tcdA (CLOD6)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 (GTD) in the presence and absence of the co-substrate UDP-glucose. While the enzymatic core is similar to that of TcdB, the proposed GTPase-binding surface differs significantly. We show that TcdA is comparable to 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 GTD release. These studies highlight the importance of cellular activation in determining the array of substrates available to the toxins once delivered into the cell.

Structural determinants of the Clostridium difficile toxin A glucosyltransferase activity.,Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, Spiller B, Lacy DB J Biol Chem. 2012 Jan 20. PMID:22267739[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, Spiller B, Lacy DB. Structural determinants of the Clostridium difficile toxin A glucosyltransferase activity. J Biol Chem. 2012 Jan 20. PMID:22267739 doi:10.1074/jbc.M111.298414

3srz, resolution 2.58Å

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