The 1.8 Å cholix toxin crystal structure in complex with NAD + and evidence for a new kinetic model

Robert J. Fieldhouse, René Jørgensen, Miguel R. Lugo, A. Rod Merrill*

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


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 1.8 ̊ 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 ADP-ribosyltransferase 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.

TidsskriftJournal of Biological Chemistry
Udgave nummer25
Sider (fra-til)21176-21188
Antal sider13
StatusUdgivet - 15 jun. 2012
Udgivet eksterntJa

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