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Title: Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae

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 (IC50 = 4.6 {+-} 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 {+-} 2 {mu}g/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-{angstrom} 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 playsmore » a significant role in the survival of the organism in an aquatic environment.« less

Authors:
; ; ; ; ;  [1];  [2];  [2]
  1. (Guelph)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1006674
Resource Type:
Journal Article
Journal Name:
J. Biol. Chem.
Additional Journal Information:
Journal Volume: 283; Journal Issue: (16) ; 04, 2008; Journal ID: ISSN 0021-9258
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; ADP; ANIMALS; ARTEMIA; CHOLERA; CRUSTACEANS; CRYSTAL STRUCTURE; CYTOPLASM; DIPHTHERIA; DISEASES; ELONGATION; ENZYMES; HOST; INHIBITION; MODIFICATIONS; PATHOGENS; PLANTS; PROTEINS; RESOLUTION; SYNTHESIS; TOXINS; TRANSFERASES; TRANSLOCATION; VIRULENCE

Citation Formats

Jorgensen, Rene, Purdy, Alexandra E., Fieldhouse, Robert J., Kimber, Matthew S., Bartlett, Douglas H., Merrill, A. Rod, NIH), and UCSD). Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae. United States: N. p., 2008. Web. doi:10.1074/jbc.M710008200.
Jorgensen, Rene, Purdy, Alexandra E., Fieldhouse, Robert J., Kimber, Matthew S., Bartlett, Douglas H., Merrill, A. Rod, NIH), & UCSD). Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae. United States. doi:10.1074/jbc.M710008200.
Jorgensen, Rene, Purdy, Alexandra E., Fieldhouse, Robert J., Kimber, Matthew S., Bartlett, Douglas H., Merrill, A. Rod, NIH), and UCSD). Tue . "Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae". United States. doi:10.1074/jbc.M710008200.
@article{osti_1006674,
title = {Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae},
author = {Jorgensen, Rene and Purdy, Alexandra E. and Fieldhouse, Robert J. and Kimber, Matthew S. and Bartlett, Douglas H. and Merrill, A. Rod and NIH) and UCSD)},
abstractNote = {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 (IC50 = 4.6 {+-} 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 {+-} 2 {mu}g/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-{angstrom} 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.},
doi = {10.1074/jbc.M710008200},
journal = {J. Biol. Chem.},
issn = {0021-9258},
number = (16) ; 04, 2008,
volume = 283,
place = {United States},
year = {2008},
month = {7}
}