Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.

Article Details

Citation

Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Merrill AR

Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.

J Biol Chem. 2008 Apr 18;283(16):10671-8. doi: 10.1074/jbc.M710008200. Epub 2008 Feb 14.

PubMed ID
18276581 [ View in PubMed
]
Abstract

The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC(50) = 4.6 +/- 0.4 ng/ml) and crustaceans (Artemia nauplii LD(50) = 10 +/- 2 mug/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-A resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Exotoxin AP11439Details
Cholix toxinQ5EK40Details