Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
The crystal structure of diphtheria toxin (DT) in complex with nicotinamide adenine dinucleotide (NAD) has been determined by x-ray crystallography to 2.3 A resolution. NAD binds to a cleft on the surface of the catalytic (C) domain of DT, interacting closely with the side chains of Tyr54, Tyr65, His21, Thr23, and Glu 48. The carboxylate group of Glu148 of Dt lies approximately 4 A from the scissile, N-glycosidic bound of NAD, suggesting a possible catalytic role for Glu148 in stabilizing a positively charged oxocarbonium intermediate. Residues 39-46 of the active-site loop of the C-domain become disordered upon NAD-binding, suggesting a potential role for these residues in binding to elongation facor-2 (EF-2). Structural alignments of the DT-NAD complex with the structures of other ADP-ribosylating toxins suggest how NAD may bind to these other enzymes.
Bell
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UCLA-DOE Lab of Structural Biology 90095-1569, USA.
Eisenberg
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D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004167:Diphtheria Toxin / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D004167:Diphtheria Toxin; D009243:NAD