Structure-activity relationships of an exotoxin of Pseudomonas aeruginosa.
The relation of the structure of Pseudomonas aeruginosa exotoxin A (PA toxin) to its enzymatic activity (adenosine 5'-diphosphate-ribosyl transferase) in vitro and to its toxicity in vivo was examined. PA toxin is produced as a single polypeptide chain with a molecular weight of about 71,500. PA toxin is produced by Pseudomonas as a toxic proenzyme that lacks enzymatic activity. Adenosine 5'-diphosphate-ribosyl transferase activity is expressed when the molecule is denatured and reduced or when its is cleaved by Pseudomonas proteases to yield an enzymatically active 27,000-dalton fragment (fragment a). A 45,000-dalton protein is tentatively identified as the enzymatically inactive fragment b of PA toxin. Enzymatically active forms of the toxin lack toxicity for mouse L-cells or mouse lethality. Thus, it is concluded that the native toxin proenzyme is required for toxicity and that a structural rearrangement must precede its intracellular activity.
D004591:Electrophoresis, Polyacrylamide Gel; D005779:Immunodiffusion; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000378:metabolism*
D014118:Toxins, Biological