Thermodynamic dissection of the substrate-ribozyme interaction in the hammerhead ribozyme

Klemens J. Hertel, Tracy K. Stage-Zimmermann, Glenyss Ammons, Olke C. Uhlenbeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The free energy of substrate binding to the hammerhead ribozyme was compared for 10 different hammerheads that differed in the length and sequence of their substrate recognition helices. These hammerheads were selected because neither ribozyme nor substrate oligonucleotide formed detectable alternate secondary structures. The observed free energies of binding varied from -8 to -24 kcal/mol and agreed very well with binding energies calculated from the nearest-neighbor free energies if a constant energetic penalty of ΔG°(core) = +3.3 ± 1 kcal/mol is used for the catalytic core. A set of substrates that contained a competing hairpin secondary structure showed weaker binding to the ribozyme by an amount consistent with the predicted free energy for hairpin formation. These thermodynamic conclusions permit the prediction of substrate binding affinities for ribozyme-substrate pairs of any helix length and sequence, and thus, should be very valuable for the rational design of ribozymes directed toward gene inactivation.

Original languageEnglish (US)
Pages (from-to)16983-16988
Number of pages6
Issue number48
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Thermodynamic dissection of the substrate-ribozyme interaction in the hammerhead ribozyme'. Together they form a unique fingerprint.

Cite this