title: Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity: identification of a novel class of ADP-ribosyltransferases.
abstract: Clostridium spiroforme iotalike toxin produced time- and concentration-dependent incorporation of ADP-ribose into homo-poly-L-arginine. Polyasparagine, polyglutamic acid, polylysine, and agmatine were poor substrates. Enzyme activity was associated with the light-chain polypeptide of the toxin. The heavy chain did not possess ADP-ribosyltransferase activity, nor did it enhance or inhibit activity of the light chain. In broken-cell assays, the toxin acted mainly on G-actin, rather than F-actin. A single ADP-ribose group was transferred to each substrate molecule (G-actin). The enzyme was heat sensitive, had a pH optimum in the range of 7 to 8, was inhibited by high concentrations of nicotinamide, and was reversibly denatured by urea and guanidine. Physiological levels of nucleotides (AMP, ADP, ATP, and ADP-ribose) and cations (Na+, K+, Ca2+, and Mg2+) were not very active as enzyme inhibitors. The toxin was structurally and functionally similar to Clostridium botulinum type C2 toxin and Clostridium perfringens iota toxin. When combined with previous findings, the data suggest that a new class of mono(ADP-ribosyl)ating toxins has been found and that these agents belong to a related and possibly homologous series of binary toxins.
authors.affiliation: Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
authors.forename: L L
authors.initials: LL
authors.lastname: Simpson
authors.forename: B G
authors.initials: BG
authors.lastname: Stiles
authors.forename: H
authors.initials: H
authors.lastname: Zepeda
authors.forename: T D
authors.initials: TD
authors.lastname: Wilkins
mesh_terms: D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000633:toxicity; D002460:Cell Line; D003013:Clostridium / Q000201:enzymology* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005057:Eukaryotic Cells / Q000187:drug effects; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009244:NAD+ Nucleosidase; D009536:Niacinamide / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats
chemical_list: D001427:Bacterial Toxins; D010455:Peptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C054948:iota toxin, Clostridium spiroforme; D000246:Adenosine Diphosphate Ribose; C015462:polyarginine; D009536:Niacinamide; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; D009699:N-Glycosyl Hydrolases; D009244:NAD+ Nucleosidase