Revisiting the planarity of nucleic acid bases: Pyramidilization at glycosidic nitrogen in purine bases is modulated by orientation of glycosidic torsion

Abstract

We describe a novel, fundamental property of nucleobase structure, namely, pyramidilization at the N1/9 sites of purine and pyrimidine bases. Through a combined analyses of ultra-high-resolution X-ray structures of both oligonucleotides extracted from the Nucleic Acid Database and isolated nucleotides and nucleosides from the Cambridge Structural Database, together with a series of quantum chemical calculations, molecular dynamics (MD) simulations, and published solution nuclear magnetic resonance (NMR) data, we show that pyramidilization at the glycosidic nitrogen is an intrinsic property. This property is common to isolated nucleosides and nucleotides as well as oligonucleotides—it is also common to both RNA and DNA. Our analysis suggests that pyramidilization at N1/9 sites depends in a systematic way on the local structure of the nucleoside. Of note, the pyramidilization undergoes stereo-inversion upon reorientation of the glycosidic bond. The extent of the pyramidilization is further modulated by the conformation of the sugar ring. The observed pyramidilization is more pronounced for purine bases, while for pyrimidines it is negligible. We discuss how the assumption of nucleic acid base planarity can lead to systematic errors in determining the conformation of nucleotides from experimental data and from unconstrained MD simulations.

Exploring ion induced folding of a single-stranded DNA oligomer from molecular simulation studies

“…[59][60][61][62] On the other hand, guanine rich oligonucleotides are known to exhibit opposite behavior. 64 In general, w corresponding to the anti-conformation has been found to vary within 901 to 1801 for the A-DNA and within 1801 to 2701 for the B-DNA. Appropriate orientation of a base with respect to the backbone sugar ring is important for stacking.…”

Evaluating the Effects of the Nonplanarity of Nucleic Acid Bases on NMR, IR, and Vibrational Circular Dichroism Spectra: A Density Functional Theory Computational Study

“…These two respective contributions to shift are equal to the λ′ and κ′ torsion angles ( Figure 1; κ′ was described previously in ref 33). Because the spin-spin pathway of 3 J(C4/2-H1′) coupling coincides with torsion at the site of the nucleobase (the…”

“…Because the geometry deformations in nucleosides depend specifically on glycosidic-bond orientation, 33 the KEs for the 3 J couplings require nontrivial (nonconstant) phase corrections. In this study, we revised the currently available KEs and used the DFT method to calculate the effects of the structural deformations on the phase of the KEs for the 3 J(C4/2-H1′) and 3 J(C8/6-H1′) scalar couplings as well as the IR and vibrational circular dichroism (VCD) spectra.…”

Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N-Glycosidic Bond of 8-OxoG with the hOGG1 DNA Repair Protein

“…The ultrahigh criteria basically ensured exclusion of all structures refined with the methods employing empirical force-fields because these may show false, typically underestimated pyramidalization. 27 Unfortunately, the resolution of 1N3C and 2NOZ structure showing oxoG inserted into the hOGG1 catalytic site was only 2.70 and 2.43 Å, respectively. We can therefore hypothesize that these structures need not show actual N9-pyramidalization of oxoG, albeit they clearly and reliably define all substrate−enzyme interactions within the catalytic core ( Figure 3).…”

“…The ultrahigh resolution must be requested. 27 Fortunately, all interactions of oxoG within the hOGG1 catalytic core were clearly determined in the crystal structures. Once the structural information was available, it was possible to calculate N9-pyramidalization.…”