NAD+-glycohydrolysis

In the absence of the G protein, PT is able to catalyze the transfer of the ADP-ribose moiety of NAD"" to a water molecule in a reaction known as NAD "-glycohydrolysis (for review, see Locht and Antoine, 1995). This property is also shared with cholera toxin. In contrast, the NAD "-glycohydrolase activities of diphtheria toxin and exotoxin A are much less efficient. The affinity of PT for NAD is in the micromolar range, as evidenced by fluorescent quenching and determina-... 

So far, only two catalytic residues have been identified in SI Glu-129 (Antoine et ai, 1993) and His-35 (Antoine and Locht, 1994). The first residue is conserved in all known ADP-ribosylating toxins, whereas His-35 is only conserved in cholera toxin and a recently identified mosquitocidal toxin produced by Bacillus sphaericus. This residue is not present in diphtheria toxin and exotoxin A (Fig. 1). The absence of this catalytic residue in the latter two toxins may explain their inefficiency in carrying out the NAD -glycohydrolysis reaction, compared to PT and cholera toxin. The acceptor substrate of diphtheria toxin and exotoxin A is diphthamide, a modified histidine residue in EF2. Perhaps this residue may take on some of the functions of the catalytic His residue in the other toxins. 

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