The selectivity for K+ versus Na+ in DNA quadruplexes is dominated by relative free energies of hydration: A thermodynamic analysis by H-1 NMR
The selectivity for K+ versus Na+ in DNA quadruplexes is dominated by relative free energies of hydration: A thermodynamic analysis by H-1 NMR
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DOI：
10.1021/bi9620565
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发表时间：
1996-12-03
期刊：
影响因子：
2.9
通讯作者：
Feigon, J
中科院分区：
文献类型：
--
作者：
Hud, NV;Smith, FW;Feigon, J
以寡核苷酸d(G(3)T(4)G(3))为模型体系，研究了Na+和K+在G四重态上的配位竞争。在氯化钠或氯化钾存在下，D(G(3)T(4)G(3))形成含有三个G四联体的二聚体折叠结构。质子化学位移是配位离子物种所特有的，它被用来监测在平衡条件下钠和钾形态之间的转化。滴定实验分析表明，至少有两个K+被二聚体分子的三个四重态配位，并且两个Na+被两个K+取代得到了完美的数据。我们的结果还表明，[d(G(3)T(4)G(3))](2)从钠形式到钾形式的转换与-1.7+/-0.15千卡/摩尔的净自由能变化(增量G度)有关。长期以来，人们一直认为，在K+存在的情况下，DNA四链结构具有更高的热稳定性，这主要是由于K+离子在G四重态形成的配位位置上的最佳匹配。然而，考虑到与钠到钾的转变有关的自由能变化相对较小，以及Na+和K+的水化自由能之间的相对较大的差异，这表明这是不正确的。相反，K+对Na+的优先配位实际上是由于相对于K+脱水，Na+脱水的能量成本更高。
We have studied the competition between Na+ and K+ for coordination by G quartets using the oligonucleotide d(G(3)T(4)G(3)) as a model system. d(G(3)T(4)G(3)) forms a dimeric foldback structure containing three G quartets in the presence of either NaCl or KCl. Proton chemical shifts, which are particular to the species of coordinated ion, have been used to monitor the conversion between the sodium and potassium forms under equilibrium conditions. Analysis of titration experiments indicates that at least two K+ are coordinated by the three quartets of the dimeric molecule, and perfect fits of the data are obtained for two Na+ being displaced by two K+ Our results also indicate that the conversion of [d(G(3)T(4)G(3))](2) from the sodium to the potassium form is associated with a net free energy change (Delta G degrees) of -1.7 +/- 0.15 kcal/mol. It has long been suggested that the greater thermal stability of DNA quadruplex structures in the presence of K+ is primarily a result of the optimal fit of this ion in the coordination sites formed by G quartets. However, a consideration of the relatively small change in free energy associated with the conversion from the sodium to the potassium form and the relatively large difference between the free energy of hydration for Na+ and K+ indicates that this cannot be correct. Rather, the preferred coordination of K+ over Na+ is actually driven by the greater energetic cost of Na+ dehydration with respect to K+ dehydration.