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Mapping the enzymatic active site of Pseudomonas aeruginosa exotoxin A
Author(s) -
Brandhuber Barbara J.,
Allured Viloya S.,
Falbel Tanya G.,
McKay David B.
Publication year - 1988
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340030303
Subject(s) - nad+ kinase , pseudomonas exotoxin , active site , biochemistry , binding site , enzyme , chemistry , diphtheria toxin , exotoxin , stereochemistry , biology , toxin , recombinant dna , gene
Pseudomonas aeruginosa exotoxin A is representative of a class of enzymes, the monoADP‐ribosyl, 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 Å, 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.