Activated Ribonucleotides Undergo a Sugar Pucker Switch upon Binding to a Single-Stranded RNA Template
Open accessAbstract
Template-directed polymerization of chemically activated ribonucleotide monomers, such as nucleotide 5'-phosphorimidazolides, has been studied as a model for nonenzymatic RNA replication during the origin of life. Kinetic studies of the polymerization of various nucleotide monomers on oligonucleotide templates have suggested that the A-form (C3'-endo sugar pucker) conformation is optimal for both monomers and templates for efficient copying. However, RNA monomers are predominantly in the C2'-endo conformation when free in solution, except for cytidine, which is approximately equally distributed between the C2'-endo and C3'-endo conformations. We hypothesized that ribonucleotides undergo a switch in sugar pucker upon binding to an A-type template and that this conformational switch allows or enhances subsequent polymerization. We used transferred nuclear Overhauser effect spectroscopy (TrNOESY), which can be used for specific detection of the bound conformation of small-molecule ligands with relatively weak affinity to receptors, to study the interactions between nucleotide 5'-phosphorimidazolides and single-stranded oligonucleotide templates. We found that the sugar pucker of activated ribonucleotides switches from C2'-endo in the free state to C3'-endo upon binding to an RNA template. This switch occurs only on RNA and not on DNA templates. Furthermore, activated 2'-deoxyribonucleotides maintain a C2'-endo sugar pucker in both the free and template-bound states. Our results provide a structural explanation for the observations that activated ribonucleotides are superior to activated deoxyribonucleotides and that RNA templates are superior to DNA templates in template-directed nonenzymatic primer-extension reactions.
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Monomers that are in the 2′-endo conformation in solution switch to the 3′-endo state upon binding to an RNA template.
“We have previously shown that monomers that are in the 2′-endo conformation in solution switch to the 3′-endo state upon binding to an RNA template.24”
From Replacing Uridine with 2-Thiouridine Enhances the Rate and Fidelity of Nonenzymatic RNA Primer Extension (2015) · cites this paper as [24]
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- Authors
- Zhang, N., Zhang, S., & Szostak, J. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Szostak, Jack W.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-02-03
- Volume
- 134
- Issue
- 8
- Pages
- 3691-3694
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC3448298
- OpenAlex
- W2113825103
- Cited by
- 53
- References
- 32
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 3
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the American Chemical Society (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Science Foundation
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- sugar pucker, template polymerization, origin of life, A-form RNA, C3'-endo conformation, C2'-endo conformation, primer extension
- MeSH terms
- Binding Sites, Carbohydrates, Models, Molecular, Ribonucleotides, RNA
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