M. Domenighini et al., COMMON FEATURES OF THE NAD-BINDING AND CATALYTIC SITE OF ADP-RIBOSYLATING TOXINS, Molecular microbiology, 14(1), 1994, pp. 41-50
Computer analysis of the three-dimensional structure of ADP-ribosylati
ng toxins showed that in all toxins the NAD-binding site is located in
a cavity. This cavity consists of 18 contiguous amino acids that form
an alpha-helix bent over a beta-strand. The tertiary folding of this
structure is strictly conserved despite the differences in the amino a
cid sequence. Catalysis is supported by two spatially conserved amino
acids, each flanking the NAD-binding site. These are: a glutamic acid
that is conserved in all toxins, and a nucleophilic residue, which is
a histidine in the diphtheria toxin and Pseudomonas exotoxin A, and an
arginine in the cholera toxin, the Escherichia coli heat-labile enter
otoxins, the pertussis toxin and the mosquitocidal toxin of Bacillus s
phaericus. The latter group of toxins presents an additional histidine
that appears important for catalysis. This structure suggests a gener
al mechanism of ADP-ribosylation evolved to work on different target p
roteins.