Determination of DNA minor groove width in distamycin-DNA complexes by solid-state NMR.
Determination of DNA minor groove width in distamycin-DNA complexes by solid-state NMR.
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DOI：
10.1093/nar/gkg720
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发表时间：
2003-09
影响因子：
14.9
通讯作者：
Gregory L. Olsen;E. Louie;G. Drobny;S. Sigurdsson
中科院分区：
文献类型：
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作者：
Gregory L. Olsen;E. Louie;G. Drobny;S. Sigurdsson
我们进行了固态31 P-19 F REDOR核磁共振（NMR）实验，以监测在不同化学计量的药物偏端霉素A结合时寡核苷酸d（CGCAAA 2 ′ FUTGGC）*d（GCCAAT（pS）TT GCG）（A3 T2）的小沟宽度的变化。在水合固态样品中，未结合DNA的小沟宽度（以2 ′ FU 7-pS19标记间距离测量）为9.4 +/-0.7 A，与类似的富含A：T的DNA的小沟宽度相当。观察到单个药物分子的结合导致沟槽宽度减小2.4 A。随后加入第二个药物分子导致更大的构象变化，将该小沟宽度扩展至13.6 A，与2：1复合物的先前溶液NMR研究的结果一致。这些31 P-19 F REDOR结果证明了固态NMR测量DNA-药物复合物中7-14 A距离的能力，并提供了直接光谱测量核酸中小沟宽度的第一个例子。
We have performed solid-state 31P-19F REDOR nuclear magnetic resonance (NMR) experiments to monitor changes in minor groove width of the oligonucleotide d(CGCAAA2'FUTGGC)*d(GCCAAT(pS)TT GCG) (A3T2) upon binding of the drug distamycin A at different stoichiometries. In the hydrated solid-state sample, the minor groove width for the unbound DNA, measured as the 2'FU7-pS19 inter-label distance, was 9.4 +/- 0.7 A, comparable to that found for similar A:T-rich DNAs. Binding of a single drug molecule is observed to cause a 2.4 A decrease in groove width. Subsequent addition of a second drug molecule results in a larger conformational change, expanding this minor groove width to 13.6 A, consistent with the results of a previous solution NMR study of the 2:1 complex. These 31P-19F REDOR results demonstrate the ability of solid-state NMR to measure distances of 7-14 A in DNA-drug complexes and provide the first example of a direct spectroscopic measurement of minor groove width in nucleic acids.