Inhibition of the hammerhead ribozyme by neomycin

Tracy K. Stage, Klemens J. Hertel, Olke C. Uhlenbeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

A series of antibiotics was tested for stimulation or inhibition of the hammerhead ribozyme cleavage reaction. Neomycin was found to be a potent inhibitor of the reaction with a K, of 13.5 μM. Two hammerheads with well-characterized kinetics were used to determine which steps in the reaction mechanism were inhibited by neomycin. The data suggest that neomycin interacts preferentially with the enzyme-substrate complex and that this interaction leads to a reduction in the cleavage rate by stabilizing the ground state of the complex and destabilizing the transition state of the cleavage step. A comparison of neomycin with other aminoglycosides and inhibitors of hammerhead cleavage implies that the ammonium ions of neomycin are important for the antibiotic-hammerhead interaction.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalRNA
Volume1
Issue number1
StatePublished - 1995

Keywords

  • Antibiotics
  • Catalytic RNA

ASJC Scopus subject areas

  • Molecular Biology

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