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.

• MeSH
• Deoxyadenosines chemistry   MeSH
• Deoxycytidine chemistry   MeSH
• Nitrogen chemistry   MeSH
• Crystallography, X-Ray MeSH
• Nuclear Magnetic Resonance, Biomolecular MeSH
• Oligonucleotides chemistry   MeSH
• Computer Simulation MeSH
• Purine Nucleosides chemistry   MeSH
• Purine Nucleotides chemistry   MeSH
• Purines chemistry   MeSH
• Pyrimidine Nucleosides chemistry   MeSH
• Pyrimidine Nucleotides chemistry   MeSH
• Pyrimidines chemistry   MeSH
• Carbohydrates chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 2'-deoxyadenosine MeSH Browser
• Deoxyadenosines MeSH
• Deoxycytidine MeSH
• Nitrogen MeSH
• Oligonucleotides MeSH
• Purine Nucleosides MeSH
• Purine Nucleotides MeSH
• Purines MeSH
• Pyrimidine Nucleosides MeSH
• Pyrimidine Nucleotides MeSH
• Pyrimidines MeSH
• Carbohydrates MeSH

Density functional theory was employed to study the dependence of 13C and 15N magnetic shielding tensors on the glycosidic torsion angle (chi) and conformation of the sugar ring in 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxythymidine. In general, the magnetic shielding of the glycosidic nitrogens and the sugar carbons was found to depend on both the conformation of the sugar ring and chi. Our calculations indicate that the magnetic shielding anisotropy of the C6 atom in pyrimidine and the C8 atom in purine bases depends strongly on chi. The remaining base carbons were found to be insensitive to both sugar pucker and chi re-orientation. These results call into question the underlying assumptions of currently established methods for interpreting residual chemical shift anisotropies and 13C and 15N auto- and cross-correlated relaxation rates and highlight possible limitations of DNA applications of these methods.

• MeSH
• Anisotropy MeSH
• DNA chemistry   metabolism   MeSH
• Carbohydrate Conformation MeSH
• Molecular Structure MeSH
• Nuclear Magnetic Resonance, Biomolecular methods   MeSH
• Purine Nucleosides chemistry   metabolism   MeSH
• Pyrimidine Nucleosides chemistry   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA MeSH
• Purine Nucleosides MeSH
• Pyrimidine Nucleosides MeSH