Mapping the enzymatic active site of Pseudomonas aeruginosa exotoxin A - PubMed (original) (raw)

Mapping the enzymatic active site of Pseudomonas aeruginosa exotoxin A

B J Brandhuber et al. Proteins. 1988.

Abstract

Pseudomonas aeruginosa exotoxin A is a representative of a class of enzymes, the mono-ADP-ribosyl transferases, which catalyze the covalent transfer of an ADP-ribose moiety of NAD+ to a target substrate. Availability of the three-dimensional structure of exotoxin A provides the opportunity for mapping substrate binding sites and suggesting which amino acid residues may be involved in catalysis. Data from several sources have been combined to develop a proposal for the NAD+ binding site of exotoxin A: the binding of NAD+ fragments adenosine, AMP, and ADP have been delineated crystallographically to 6.0, 6.0, and 2.7 A, respectively; significant sequence homology spanning 60 residues has been found between exotoxin A and diphtheria toxin, which has the identical enzymatic activity; iodination of exotoxin A, under conditions in which only tyrosine 481 is iodinated in the enzymatic domain, abolishes ADP-ribosyl transferase activity.

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