Revisiting the planarity of nucleic acid bases: Pyramidilization at glycosidic nitrogen in purine bases is modulated by orientation of glycosidic torsion.
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.
Institute of Organic Chemistry and Biochemistry AS CR, v.v.i. Flemingovo namesti 2, CZ, 16610 Prague, Czech Republic.
Vladimir
V
Sychrovsky
Silvie
S
Foldynova-Trantirkova
Nada
N
Spackova
Koen
K
Robeyns
Luc
L
Van Meervelt
Wulf
W
Blankenfeldt
Zuzana
Z
Vokacova
Jiri
J
Sponer
Lukas
L
Trantirek
D002241:Carbohydrates / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003839:Deoxyadenosines / Q000737:chemistry; D003841:Deoxycytidine / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000737:chemistry; D011684:Purine Nucleosides / Q000737:chemistry*; D011685:Purine Nucleotides / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D011742:Pyrimidine Nucleotides / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry
D002241:Carbohydrates; D003839:Deoxyadenosines; D009841:Oligonucleotides; D011684:Purine Nucleosides; D011685:Purine Nucleotides; D011687:Purines; D011741:Pyrimidine Nucleosides; D011742:Pyrimidine Nucleotides; D011743:Pyrimidines; D003841:Deoxycytidine; D009584:Nitrogen; C058118:2'-deoxyadenosine