Altering molecular recognition of RNA aptamers by allosteric selection

Garrett Soukup, Gail A M Emilsson, Ronald R. Breaker

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

In a continuing effort to explore structural and functional dynamics in RNA catalysis, we have created a series of allosteric hammerhead ribozymes that are activated by theophylline. Representative ribozymes exhibit greater than 3000-fold activation upon effector-binding and cleave with maximum rate constants that are equivalent to the unmodified hammerhead ribozyme. In addition, we have evolved a variant allosteric ribozyme that exhibits an effector specificity change from theophylline to 3-methylxanthine. Molecular discrimination between the two effectors appears to be mediated by subtle conformational differences that originate from displacement of the phosphodiester backbone near the effector binding pocket. These findings reveal the importance of abstruse aspects of molecular recognition by nucleic acids that are likely to be unapproachable by current methods of rational design. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)623-632
Number of pages10
JournalJournal of Molecular Biology
Volume298
Issue number4
DOIs
StatePublished - May 12 2000

Fingerprint

Nucleotide Aptamers
Catalytic RNA
Theophylline
Catalysis
Nucleic Acids
RNA
hammerhead ribozyme
3-methylxanthine

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Altering molecular recognition of RNA aptamers by allosteric selection. / Soukup, Garrett; Emilsson, Gail A M; Breaker, Ronald R.

In: Journal of Molecular Biology, Vol. 298, No. 4, 12.05.2000, p. 623-632.

Research output: Contribution to journalArticle

Soukup, Garrett ; Emilsson, Gail A M ; Breaker, Ronald R. / Altering molecular recognition of RNA aptamers by allosteric selection. In: Journal of Molecular Biology. 2000 ; Vol. 298, No. 4. pp. 623-632.
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