Histidine 21 is at the NAD+ binding site of diphtheria toxin.
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.
Papini
E
E
Centro Consiglio Nazionale delle Ricerche Biomembrane, Universitá di Padova, Italy.
Schiavo
G
G
Sandoná
D
D
Rappuoli
R
R
Montecucco
C
C
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
D004167:Diphtheria Toxin; D005561:Formates; D010446:Peptide Fragments; D009243:NAD; D009536:Niacinamide; D006639:Histidine; D000225:Adenine; D000241:Adenosine; D004047:Diethyl Pyrocarbonate