Projects per year
Abstract
We describe the multifactorial origins of catalysis by the twister ribozyme. We provide evidence that the adenine immediately 3′ to the scissile phosphate (A1) acts as a general acid. Substitution of ring nitrogen atoms indicates that very unusually the N3 of A1 is the proton donor to the oxyanion leaving group. A1 is accommodated in a specific binding pocket that raises its pKa toward neutrality, juxtaposes its N3 with the O5′ to be protonated, and helps create the in-line trajectory required for nucleophilic attack. A1 performs general acid catalysis while G33 acts as a general base. A 100-fold stereospecific phosphorothioate effect at the scissile phosphate is consistent with a significant stabilization of the transition state by the ribozyme, and functional group substitution at G33 indicates that its exocyclic N2 interacts directly with the scissile phosphate. A model of the ribozyme active site is proposed that accommodates these catalytic strategies.
Original language | English |
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Pages (from-to) | 6151-6162 |
Number of pages | 12 |
Journal | Journal of the American Chemical Society |
Volume | 138 |
Issue number | 19 |
Early online date | 6 May 2016 |
DOIs | |
Publication status | Published - 18 May 2016 |
ASJC Scopus subject areas
- General Chemistry
- Catalysis
- Biochemistry
- Colloid and Surface Chemistry
Fingerprint
Dive into the research topics of 'The Novel Chemical Mechanism of the Twister Ribozyme'. Together they form a unique fingerprint.Projects
- 2 Finished
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Dynamics of Eukaryotic Junction-Resolving Enzyme GEN1 - DNA Junction Interactions
Lilley, D. (Investigator)
Biotechnology and Biological Sciences Research Council
1/10/16 → 30/09/19
Project: Research
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Fluorescence Resonance Energy Transfer as a Rich Source of Orientational Information in Nucleic Acid Structure
Lilley, D. (Investigator)
Engineering and Physical Sciences Research Council
1/09/12 → 30/06/16
Project: Research
Profiles
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Lilley, David
- Molecular Cell and Developmental Biology - Professor of Molecular Biology
Person: Academic