Toxins as Tools in Characterization of Heterotrimeric G-proteins

Two bacterial toxins, namely pertussis toxin and cholera toxin, were of great importance in determining the function of G-proteins. Both toxins catalyze ADP ribosyla-tion of proteins. Dming ADP ribosylation, an ADP-ribose residue is transferred from NAD to an amino acid residue of a substrate protein (Fig. 5.15). 

Constitutive activation of Gs-proteins by cholera toxin is the cause of the devastating effect of the cholera bacterimn. Vibrio cholerae, on the water content of the intestine. Due to the lack of deactivation of the Gs-protein, adenylyl cyclase next in the reaction sequence is constantly activated, so that the level of cAMP in the cells of the intestinal epithelium is greatly increased. This, in turn, leads to increased active transport of ions and an excessive efflux of water and Na takes place in the intestine. 

Pertussis toxin, formed by Bortedella pertussis, the causative organism of whooping cough, carries out an ADP-ribosylation at a cysteine residue close to the C-terminus of 

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