title: A survey of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) as inhibitors of ribosome-inactivating proteins (RIPs).
abstract: The inhibitory power of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) on the RNA-N-glycosidase activity catalyzed by bacterial (Shiga toxin 1) and plant (ricin, gelonin, momordin, bryodin-R, PAP-S, luffin, trichosantin, saporin 6 and barley) RIPs has been compared. The behavior of the two inhibitors is largely variable. While Shiga toxin 1 is preferentially inhibited by 4-APP, plant RIPs are either preferentially inhibited by adenine, or equally inhibited by the two compounds or, finally, only slightly more by 4-APP. Sequence variabilities involved in these different behaviors are discussed. The experimental data clearly indicate that, in spite of the same mechanism of action, RIPs differ widely in the ability to fit small ring molecules in the active cleft. While the strong inhibitory power of 4-APP on Shiga toxin 1 opens perspectives of therapeutic interventions, the ineffectiveness of the compound on ricin precludes its use as a suitable antidote in poisoning.
authors.affiliation: Dipartimento di Patologia sperimentale dell 'Università degli Studi di Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Brigotti
authors.forename: S
authors.initials: S
authors.lastname: Rizzi
authors.forename: D
authors.initials: D
authors.lastname: Carnicelli
authors.forename: L
authors.initials: L
authors.lastname: Montanaro
authors.forename: S
authors.initials: S
authors.lastname: Sperti
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001156:Artemia; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D054788:Ribosome Inactivating Proteins; D012270:Ribosomes / Q000187:drug effects* / Q000201:enzymology; D022621:Shiga Toxin / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; C004420:4-aminopyrazolo(3,4-d)pyrimidine; D022621:Shiga Toxin; D009699:N-Glycosyl Hydrolases; D054788:Ribosome Inactivating Proteins; D000225:Adenine