Dataset Information

Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.

ABSTRACT: In this paper using quantum-mechanical (QM) calculations in combination with Bader's quantum theory of "Atoms in Molecules" (QTAIM) in the continuum with ? = 1, we have theoretically demonstrated for the first time that revealed recently highly-energetic conformers of the classical A·T DNA base pairs - Watson-Crick [A·T(wWC)], reverse Watson-Crick [A·T(wrWC)], Hoogsteen [A·T(wH)] and reverse Hoogsteen [A·T(wrH)] - act as intermediates of the intrapair mutagenic tautomerization of the T nucleobase owing to the novel tautomerisation pathways: A·T(wWC)?A·T*(w? WC); A·T(wrWC)?A· TO2* (w? rWC); A·T(wH)?A·T*(w? H); A·T(wrH)?A· TO2* (w? rH). All of them occur via the transition states as tight ion pairs (A+, protonated by the N6H2 amino group)·(T-, deprotonated by the N3H group) with quasi-orthogonal geometry, which are stabilized by the participation of the strong (A)N6+H···O4-/O2-(T) and (A)N6+H···N3-(T) H-bonds. Established tautomerizations proceed through a two-step mechanism of the protons moving in the opposite directions along the intermolecular H-bonds. Initially, proton moves from the N3H imino group of T to the N6H2 amino group of A and then subsequently from the protonated N6+H3 amino group of A to the O4/O2 oxygen atom of T, leading to the products - A·T*(w? WC), A· TO2* (w? rWC), A·T*(w? H), and A· TO2* (w? rH), which are substantially non-planar, conformationally-labile complexes. These mispairs are stabilized by the participation of the (A)N6H/N6H'···N3(T) and (T)O2H/O4H···N6(A) H-bonds, for which the pyramidalized amino group of A is their donor and acceptor. The Gibbs free energy of activation of these mutagenic tautomerizations lies in the range of 27.8-29.8 kcal·mol-1 at T = 298.15 K in the continuum with ? = 1.

SUBMITTER: Brovarets' OO

PROVIDER: S-EPMC6277528 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.

Brovarets' Ol'ha O OO Tsiupa Kostiantyn S KS Dinets Andrii A Hovorun Dmytro M DM

Frontiers in chemistry 20181127

In this paper using quantum-mechanical (QM) calculations in combination with Bader's quantum theory of "Atoms in Molecules" (QTAIM) in the continuum with ε = 1, we have theoretically demonstrated for the first time that revealed recently highly-energetic conformers of the classical A·T DNA base pairs - Watson-Crick [A·T(wWC)], reverse Watson-Crick [A·T(wrWC)], Hoogsteen [A·T(wH)] and reverse Hoogsteen [A·T(wrH)] - act as intermediates of the intrapair ...[more]

PMID: 30538979

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Dataset Information

Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.

Publications

Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.

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