Mapping the enzymatic active site of Pseudomonas aeruginosa exotoxin A

✍ Scribed by Barbara J. Brandhuber; Viloya S. Allured; Tanya G. Falbel; David B. McKay

• Book ID: 105358411
• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 979 KB
• Volume: 3
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/prot.340030303

✦ Synopsis

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.