The hairpin structure of a topoisomerase II site DNA strand analyzed by combined NMR and energy minimization methods

Journal of Molecular Biology
A Amir-AslaniS Fermandjian

Abstract

We report on the structural study of the single-stranded 19mer oligonucleotide d(AGCTTATC-ATC-GATAAGCT) 22(+). This corresponds to the 15-to-33(+) strand of pBR322 DNA belonging to a strong cleavage site (site 22) for topoisomerase II coupled to antitumor drugs VP-16 or ellipticine. The partially self-complementary nature of this oligonucleotide makes likely its folding into a hairpin structure. To assess this property we carried out a quantitative analysis based on joint calculations and NMR experiments. The latter required two-dimensional (NOESY, P-COSY, TOCSY and proton-detected 1H-31P), and three-dimensional (NOESY-TOCSY) spectra to achieve the assignment of the overcrowded sugar H4' ad H5'/H5" proton region. For molecular modeling, the JUMNA program was used together with NMR constraints; namely, the distances and the backbone torsion angles provided by NOEs and homo- and heteronuclear coupling constants. Experimental results proved that the 19mer oligonucleotide adopted a stable hairpin structure characterized by an eight base-pair stem and a three-membered loop (central-ATC-segment). Homonuclear 1H-1H and heteronuclear 1H-31P coupling constant measurements provided information on the conformational heterogeneity of the s...Continue Reading

Citations

May 9, 2003·Nucleic Acids Research·Shan-Ho ChouAndrew H-J Wang
Oct 1, 2008·Nucleic Acids Research·Anette Thyssen JonstrupAnni H Andersen
Jan 16, 2002·Journal of Biomolecular Structure & Dynamics·C El AmriS Fermandjian
Jan 1, 2000·Journal of Biomolecular Structure & Dynamics·P AichJ S Lee

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