Chemical modification of islet-activating protein, pertussis toxin. Essential role of free amino groups in its lymphocytosis-promoting activity.
Chemical modification of amino groups in the molecule of islet-activating protein (IAP), pertussis toxin, resulted in differential modification of biological activities of the toxin estimated in vivo with rats. Acetamidination of epsilon-amino groups of 50% (or more) of lysine residues in the IAP molecule totally abolished the lymphocytosis-promoting activity, but exerted no effects on the epinephrine-hyperglycemia inhibitory activity, of the toxin. Both activities were abolished by acylation of 50% or more of the amino groups probably due to the destruction of the toxin's quarternary structure. In contrast, the subunit assembly of IAP was maintained after exhaustive acetamidination of its lysine residues. The ADP-ribosyltransferase (or NAD-glycohydrolase) activity of the A-promoter (the biggest subunit) of IAP, which is responsible for the principal action of the toxin, enhancing insulin secretory responses and thereby inhibiting epinephrine hyperglycemia, was not affected by acetamindination of lysine residues. Thus, the A-protomer moiety of IAP is not directly involved in, but the amino groups of lysine residues in other subunits are selectively essential for, the development of the toxin-induced lymphocytosis.
D000215:Acylation; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism; D007202:Indicators and Reagents; D008214:Lymphocytes / Q000187:drug effects; D008218:Lymphocytosis / Q000139:chemically induced*; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella
D000596:Amino Acids; D001427:Bacterial Toxins; D001786:Blood Glucose; D007202:Indicators and Reagents; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D004837:Epinephrine