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Cited by 24DNA and Nucleic Acid ChemistryAdvanced NMR Techniques and ApplicationsRNA and protein synthesis mechanisms

Probing conformational transitions towards mutagenic Watson–Crick-like G·T mismatches using off-resonance sugar carbon R1ρ relaxation dispersion

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Rangadurai, Atul, Szymanski, Eric S., Kimsey, Isaac, Shi, Honglue, Al-Hashimi, Hashim M.·2020·Journal of Biomolecular NMR
DOI 10.1007/s10858-020-00337-7PMC PMC7508749
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Abstract

NMR off-resonance R1ρ relaxation dispersion measurements on base carbon and nitrogen nuclei have revealed that wobble G·T/U mismatches in DNA and RNA duplexes exist in dynamic equilibrium with short-lived, low-abundance, and mutagenic Watson–Crick-like conformations. As Watson–Crick-like G·T mismatches have base pairing geometries similar to Watson–Crick base pairs, we hypothesized that they would mimic Watson–Crick base pairs with respect to the sugar-backbone conformation as well. Using off-resonance R1ρ measurements targeting the sugar C3′ and C4′ nuclei, a structure survey, and molecular dynamics simulations, we show that wobble G·T mismatches adopt sugar-backbone conformations that deviate from the canonical Watson–Crick conformation and that transitions toward tautomeric and anionic Watson–Crick-like G·T mismatches restore the canonical Watson–Crick sugar-backbone. These measurements also reveal kinetic isotope effects for tautomerization in D 2 O versus H 2 O, which provide experimental evidence in support of a transition state involving proton transfer. The results provide additional evidence in support of mutagenic Watson–Crick-like G·T mismatches, help rule out alternative inverted wobble conformations in the case of anionic G·T−, and also establish sugar carbons as new non-exchangeable probes of this exchange process.

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  • Rangadurai et al. reported a kinetic isotope effect as the rate of exchange between the two conformations of the G-T mismatch was approximately 3-fold slower in D2O than in H2O.

    “The authors reported a KIE as the rate of exchange between the two conformations of the mismatch was ~3-fold slower in D 2 O than in H 2 O.”

    From An open quantum systems approach to proton tunnelling in DNA (2022) · cites this paper as [52]

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Cited by

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Authors
Rangadurai, A., Szymanski, E. S., Kimsey, I., Shi, H., & Al-Hashimi, H. M.
Affiliations
Duke University (US)
ORCID
Venue
Journal of Biomolecular NMR
Publisher
Springer Science and Business Media LLC
Published
2020-08-12
Volume
74
Issue
8-9
Pages
457-471
ISSN
  • 0925-2738 (ISSN-L)
  • 1573-5001
DOI
10.1007/s10858-020-00337-7
PMC
PMC7508749
OpenAlex
W3048419264
Cited by
24
References
2
Citations by year
2026: 3 · 2025: 7 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 1
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biomolecular NMR (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (P01GM0066275)
  • National Institutes of Health (R01GM089846)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
wobble pairing, DNA conformational dynamics, tautomerism, kinetic isotope effects, proton transfer, RNA duplex
MeSH terms
Sugars, Carbon, DNA, Hydrogen Bonding, Models, Molecular, Nucleic Acid Conformation, Thymine, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Base Pairing, Base Pair Mismatch

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