The pseudodisaccharides: a novel class of group I intron splicing inhibitors.
Lysinomicin, a naturally-occurring pseudodisaccharide, inhibits translation in prokaryotes. We report that lysinomicin (and three related compounds) are able to inhibit the self-splicing of group I introns, thus identifying pseudodisaccharides as a novel class of group I intron splicing inhibitors. Lysinomicin inhibited the self-splicing of the sunY intron of phage T4 with a Ki of 8.5 microM (+/- 5 microM) and was active against other group I introns. Inhibition was found to be competitive with the substrate guanosine, unlike aminoglycoside antibiotics, which act non-competitively to inhibit the splicing of group I introns. Competitive inhibitors of group I intron splicing known to date all contain a guanidino group that was thought to be required for inhibition; lysinomicin lacks a guanidino group.
Rogers
J
J
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Davies
J
J
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D017122:Bacteriophage T4 / Q000235:genetics; D001667:Binding, Competitive; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006151:Guanosine / Q000494:pharmacology; D007438:Introns / Q000235:genetics; D007700:Kinetics; D008780:Methyltransferases / Q000235:genetics; D012326:RNA Splicing / Q000187:drug effects*; D013768:Tetrahymena / Q000235:genetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004187:Disaccharides; D006151:Guanosine; C023385:fortimicin B; C036711:lysinomicin; C023384:fortimicin A; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase