1tox
DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD
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OverviewOverview
Diphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of, Corynebacterium diphtheriae, causes the disease diphtheria in humans by, gaining entry into the cytoplasm of cells and inhibiting protein, synthesis. Specifically, the catalytic (C) domain of DT transfers the, ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2, inactive. In order to investigate how the C-domain of DT binds NAD and, catalyzes the ADP-ribosylation of EF-2, the crystal structure of DT in, complex with NAD has been determined to 2.3 A resolution. This is the, first crystal structure of an ADP-ribosyltransferase (ADP-RT) enzyme in, complex with NAD and suggests the features of the ADP-RT fold which are, important for NAD binding. The conformation of NAD in the complex and the, proximity of the Glu148 carboxylate group of the C-domain to the scissile, N-glycosidic bond of NAD suggest plausible modes of catalysis of the, ADP-ribosylation reaction. Residues 39-46 of the active-site loop of the, C-domain become disordered upon NAD binding, suggesting a potential role, for this loop in the recognition of the ADP-ribose acceptor substrate, EF-2. The negatively charged phosphates and two ribose hydroxyls of NAD, are not in direct contact with any atoms of the C-domain. Instead, they, form an exposed surface which appears to be presented for recognition by, EF-2. Structural alignments of the DT-NAD complex with the structures of, other members of the ADP-RT family suggest how NAD may bind to these other, enzymes.
About this StructureAbout this Structure
1TOX is a Single protein structure of sequence from Corynephage beta with NAD as ligand. Active as NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide., Bell CE, Eisenberg D, Biochemistry. 1996 Jan 30;35(4):1137-49. PMID:8573568
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