3Q9O

Full-length Cholix toxin from Vibrio cholerae in complex with NAD

Summary for 3Q9O

• Entry DOI: 10.2210/pdb3q9o/pdb
• Related: 2Q5T 2Q6M 3ESS
• Descriptor: exotoxin A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: receptor binding domain, beta barrel, translocation, six alpha-helix bundle, alpha-beta complex, adp-ribosylating factor, diphthamide on eukaryotic elongation factor 2, transferase
• Biological source: Vibrio cholerae
• Total number of polymer chains: 1
• Total formula weight: 72812.69

Authors

Merrill, A.R.,Jorgensen, R.,Fieldhouse, R.J. (deposition date: 2011-01-09, release date: 2012-01-04, Last modification date: 2024-10-30)

Primary citation

Fieldhouse, R.J.,Jorgensen, R.,Lugo, M.R.,Merrill, A.R.
The 1.8 a cholix toxin crystal structure in complex with NAD+ and evidence for a new kinetic model.
J.Biol.Chem., 287:21176-21188, 2012

PubMed Abstract: 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 Å 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.

PubMed: 22535961
DOI: 10.1074/jbc.M111.337311

Experimental method

X-RAY DIFFRACTION (1.793 Å)