
DOI . ORG {
}
Title[redir]:
Probing conformational transitions towards mutagenic WatsonâCrick-like G¡T mismatches using off-resonance sugar carbon R1Ď relaxation dispersion | Journal of Biomolecular NMR
Description:
NMR off-resonance R1Ď 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 WatsonâCrick-like conformations. As WatsonâCrick-like G¡T mismatches have base pairing geometries similar to WatsonâCrick base pairs, we hypothesized that they would mimic WatsonâCrick base pairs with respect to the sugar-backbone conformation as well. Using off-resonance R1Ď measurements targeting the sugar C3Ⲡand C4Ⲡnuclei, a structure survey, and molecular dynamics simulations, we show that wobble G¡T mismatches adopt sugar-backbone conformations that deviate from the canonical WatsonâCrick conformation and that transitions toward tautomeric and anionic WatsonâCrick-like G¡T mismatches restore the canonical WatsonâCrick sugar-backbone. These measurements also reveal kinetic isotope effects for tautomerization in D2O versus H2O, which provide experimental evidence in support of a transition state involving proton transfer. The results provide additional evidence in support of mutagenic WatsonâCrick-like G¡T mismatches, help rule out alternative inverted wobble conformations in the case of anionic G¡Tâ, and also establish sugar carbons as new non-exchangeable probes of this exchange process.
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Keywords {đ}
google, scholar, wobble, mismatches, dna, exchange, wclike, sugar, chemical, supplementary, conformation, bps, nmr, mismatch, fig, base, data, shifts, kimsey, measurements, anionic, sugarbackbone, state, inverted, tautomeric, structures, nucleic, hoogsteen, figure, formation, ads, acids, chem, structure, relaxation, watsoncrick, pairs, methods, offresonance, shift, observed, ppm, obtained, expected, profiles, res, biol, canonical, form, parameters,
Topics {âď¸}
c-g-c-g-a-a-t-t-c-a-c c-g-t-g-a-a-t-t-c-g-c base c6-h6/c2-h2/c8-h8 resonances canonical gua-cyt base-pairs watson-crick/hoogsteen breathing dynamics low-abundance short-lived wc n1-methyl deoxy guanosine canonical watsonâcrick sugar-backbone anti-hiv nucleoside 5-aza-5 low spin-lock fields longitudinal 13c/15n magnetization 13c/15n rf fields visualizing transient watson-crick 13c/15n spin-lock glen-pak dna cartridges gac/gc-cgc/gc-ggc resonance 13c/15n r1Ď article download pdf trna-mrna mini-helix uridine 5-oxyacetic acid n-site chemical exchange watsonâcrick base pairs sugar-backbone geometry typical unique sugar-backbone conformation hydrogen bond register full size image m1g6-c14+ hoogsteen bp favors anionic watson-crick sugar-backbone conformation differs polymerase active site canonical watsonâcrick conformation watsonâcrick duplex fragments t-c4Ⲡchemical shifts rare tautomers form r2 free-precession relaxation canonical sugar-backbone conformations nucleic acid species dna damage repair c2â˛-endo sugar pucker nmr relaxation dispersion joungâcheatham ion parameters catalytically active conformations canonical c2â˛-endo conformation dna double helix dt form watson-crick g6-c14 hoogsteen bp disrupt a-rna structure gc-cgc/gc-ggc c8-h8 assignments blochâmcconnell equations assuming
Questions {â}
- Brovarets OO, Hovorun DM (2015) How many tautomerization pathways connect Watson-Crick-like G*T DNA base mispair and wobble mismatches?
- Hansen DF, Vallurupalli P, Lundstrom P, Neudecker P, Kay LE (2008b) Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: how well can we do?
- Rangadurai A et al (2018) Why are Hoogsteen base pairs energetically disfavored in A-RNA compared to B-DNA?
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headline:Probing conformational transitions towards mutagenic WatsonâCrick-like G¡T mismatches using off-resonance sugar carbon R1Ď relaxation dispersion
description:NMR off-resonance R1Ď 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 WatsonâCrick-like conformations. As WatsonâCrick-like G¡T mismatches have base pairing geometries similar to WatsonâCrick base pairs, we hypothesized that they would mimic WatsonâCrick base pairs with respect to the sugar-backbone conformation as well. Using off-resonance R1Ď measurements targeting the sugar C3Ⲡand C4Ⲡnuclei, a structure survey, and molecular dynamics simulations, we show that wobble G¡T mismatches adopt sugar-backbone conformations that deviate from the canonical WatsonâCrick conformation and that transitions toward tautomeric and anionic WatsonâCrick-like G¡T mismatches restore the canonical WatsonâCrick sugar-backbone. These measurements also reveal kinetic isotope effects for tautomerization in D2O versus H2O, which provide experimental evidence in support of a transition state involving proton transfer. The results provide additional evidence in support of mutagenic WatsonâCrick-like G¡T mismatches, help rule out alternative inverted wobble conformations in the case of anionic G¡Tâ, and also establish sugar carbons as new non-exchangeable probes of this exchange process.
datePublished:2020-08-12T00:00:00Z
dateModified:2020-08-12T00:00:00Z
pageStart:457
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Tautomers
Anions
Replication error
Nucleic acid dynamics
Chemical exchange
Sugar pucker
Biological and Medical Physics
Biophysics
Biochemistry
general
Spectroscopy/Spectrometry
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headline:Probing conformational transitions towards mutagenic WatsonâCrick-like G¡T mismatches using off-resonance sugar carbon R1Ď relaxation dispersion
description:NMR off-resonance R1Ď 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 WatsonâCrick-like conformations. As WatsonâCrick-like G¡T mismatches have base pairing geometries similar to WatsonâCrick base pairs, we hypothesized that they would mimic WatsonâCrick base pairs with respect to the sugar-backbone conformation as well. Using off-resonance R1Ď measurements targeting the sugar C3Ⲡand C4Ⲡnuclei, a structure survey, and molecular dynamics simulations, we show that wobble G¡T mismatches adopt sugar-backbone conformations that deviate from the canonical WatsonâCrick conformation and that transitions toward tautomeric and anionic WatsonâCrick-like G¡T mismatches restore the canonical WatsonâCrick sugar-backbone. These measurements also reveal kinetic isotope effects for tautomerization in D2O versus H2O, which provide experimental evidence in support of a transition state involving proton transfer. The results provide additional evidence in support of mutagenic WatsonâCrick-like G¡T mismatches, help rule out alternative inverted wobble conformations in the case of anionic G¡Tâ, and also establish sugar carbons as new non-exchangeable probes of this exchange process.
datePublished:2020-08-12T00:00:00Z
dateModified:2020-08-12T00:00:00Z
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Tautomers
Anions
Replication error
Nucleic acid dynamics
Chemical exchange
Sugar pucker
Biological and Medical Physics
Biophysics
Biochemistry
general
Spectroscopy/Spectrometry
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