Nucleic Acids Research Advance Access published online on September 28, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp783
Structural Biology |
Revisiting the planarity of nucleic acid bases: Pyramidilization at glycosidic nitrogen in purine bases is modulated by orientation of glycosidic torsion
1Institute of Organic Chemistry and Biochemistry AS CR, v.v.i. Flemingovo namesti 2, CZ, 16610 Prague, Czech Republic, 2Biology Centre AS CR, v.v.i. & University of South Bohemia, Branisovska 31, 37005 Ceske Budejovice, Czech Republic, 3Institute of Biophysics AS CR, v.v.i. Kralovopolska 135, 61265 Brno, Czech Republic, 4Chemistry Department, Biomolecular Architecture, Celestijnenlaan 200F, 3001 Leuven (Haverlee), Belgium and 5Max-Planck-Institute of Molecular Physiology, Department of Physical Biochemistry, Otto-Hahn-Str. 11, 44227 Dortmund, Germany
*To whom correspondence should be addressed. Tel: +31 30 253 4111; Fax: +31 30 254 0980; Email: L.Trantirek{at}uu.nl
Received July 17, 2009. Revised September 2, 2009. Accepted September 5, 2009.
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.
Present addresses: Silvie Foldynova-Trantirkova, Department of Experimental Oncology, Utrecht Medical Centre, Utrecht, The Netherlands.
Lukas Trantirek, Department of Chemistry, Utrecht University, Utrecht, The Netherlands.