title: Histidine 21 is at the NAD+ binding site of diphtheria toxin.
abstract: Treatment of fragment A chain of diphtheria toxin (DT-A) with diethylpyrocarbonate modifies His-21, the single histidine residue present in the chain, without alteration of other residues. Parallel to histidine modification, NAD+ binding and the NAD-glycohydrolase and ADP-ribosyltransferase activities of DT-A are lost. Both NAD+ and adenosine are very effective in protecting DT-A from histidine modification and in preserving its biological properties, while adenine is ineffective. Reversal of histidine modification with hydroxylamine restores both NAD+ binding and enzymatic activities of the toxin. The possible role of His-21 in the activity of diphtheria toxin is discussed in relation to the available three-dimensional structure of the related toxin produced by Pseudomonas aeruginosa.
authors.affiliation: Centro Consiglio Nazionale delle Ricerche Biomembrane, Universitá di Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Papini
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: D
authors.initials: D
authors.lastname: Sandoná
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D001665:Binding Sites; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D004167:Diphtheria Toxin / Q000378:metabolism*; D005561:Formates / Q000494:pharmacology*; D006639:Histidine; D007700:Kinetics; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism; D010446:Peptide Fragments
chemical_list: D004167:Diphtheria Toxin; D005561:Formates; D010446:Peptide Fragments; D009243:NAD; D009536:Niacinamide; D006639:Histidine; D000225:Adenine; D000241:Adenosine; D004047:Diethyl Pyrocarbonate