8QDU

Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions

Summary for 8QDU

• Entry DOI: 10.2210/pdb8qdu/pdb
• NMR Information: BMRB: 34856
• Descriptor: DNA (5'-D(*(FC)P*GP*(FC)P*GP*(FC)P*G)-3') (1 entity in total)
• Functional Keywords: 2'f-ana, 2'f-rna, z-dna, dna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 3728.36

Authors

El-Khoury, R.,Cabrero, C.,Movilla, S.,Thorpe, J.D.,Roman, M.,Orozco, M.,Gonzalez, C.,Damha, M.J. (deposition date: 2023-08-30, release date: 2024-06-26, Last modification date: 2024-07-31)

Primary citation

El-Khoury, R.,Cabrero, C.,Movilla, S.,Kaur, H.,Friedland, D.,Dominguez, A.,Thorpe, J.D.,Roman, M.,Orozco, M.,Gonzalez, C.,Damha, M.J.
Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.
Nucleic Acids Res., 52:7414-7428, 2024

PubMed Abstract: Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1. The effect of the two nucleotides is so dramatic that Z-form duplexes are the only species observed in 10 mM sodium phosphate buffer and neutral pH, and no B-form is observed at any temperature. Hence, in contrast to other studies reporting formation of Z/B-form equilibria by a preference for purine glycosidic angles in syn, our NMR and computational work revealed that sequential 2'F…H2N and intramolecular 3'H…N3' interactions stabilize the left-handed helix. The equilibrium between B- and Z- forms is slow in the 19F NMR time scale (≥ms), and each conformation exhibited unprecedented chemical shift differences in the 19F signals. This observation led to a reliable estimation of the relative population of B and Z species and enabled us to monitor B-Z transitions under different conditions. The unique features of 2'F-modified DNA should thus be a valuable addition to existing techniques for specific detection of new Z-binding proteins and ligands.

PubMed: 38874502
DOI: 10.1093/nar/gkae508

Experimental method

SOLUTION NMR