25 April 2012: Article published in Journal of Biological Chemistry

Article published in Journal of Biological Chemistry.

Fieldhouse RJ, Jørgensen R, Lugo MR, Merrill AR The 1.8 angstrom cholix toxin crystal structure in complex with NAD+ and evidence for a new kinetic model. 2012; 287(25), 21176-21188 (impact factor: 5.33) PubMed.


Certain Vibrio cholerae strains produce cholix, a potent protein toxin that has diphthamide-specific ADP-ribosyltransferase activity against eukaryotic elongation factor 2. Here we present a 1.8A crystal structure of cholix in complex with its natural substrate, nicotinamide adenine dinucleotide (NAD+). We also substituted hallmark catalytic residues by site-directed mutagenesis and analyzed both NAD+ binding and ADPribosyltransferase activity using a fluorescence-based assay. These data are the basis for a new kinetic model of cholix toxin activity. Further, the new structural data serve as a reference for continuing inhibitor development for this toxin class.


René Jørgensen
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