Energetics and kinetics of a conformational switch in G-quadruplex DNA.
Energetics and kinetics of a conformational switch in G-quadruplex DNA.
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DOI：
10.1021/jp809578f
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发表时间：
2009-03-05
期刊：
影响因子：
--
通讯作者：
Chaires JB
中科院分区：
文献类型：
--
作者：
Gray RD;Li J;Chaires JB
使用圆二色性和差示扫描量热法测定由序列d[AGGG(TTAGGG)3]形成的人端粒四链体在钠篮形式和钾杂化形式之间构象转换的能量学。发现分隔两种构象的能垒很小，仅为 1.4−2.4 kcal mol−1。通过测量伴随阳离子交换反应的圆二色光谱随时间的变化来评估结合的K+与Na+阳离子的交换动力学以及伴随的构象转换。研究发现这些变化的时间过程由三个不同的动力学过程组成：一个在 5 毫秒内完成的快速阶段，随后是两个较慢的阶段，在 25 °C 和 pH 7.0 下，弛豫时间分别为 40−50 s 和 600−800 s。我们用一个模型来解释这些动力学，在该模型中，结合的 Na+ 阳离子迅速被 K+ 取代，然后进行相对缓慢的结构重排，生成最终的 K+ 结合产物。圆二色性研究表明，卟啉 TmPyP4 的添加促进了篮子向杂化形式的转化。 TmPyP4 诱导的构象变化的动力学与阳离子交换反应中观察到的相同。
Circular dichroism and differential scanning calorimetry were used to determine the energetics of the conformational switch of the human telomere quadruplex formed by the sequence d[AGGG(TTAGGG)3] between the sodium basket form and the potassium hybrid form. The energy barrier separating the two conformations was found to be modest, only 1.4−2.4 kcal mol−1. The kinetics of exchange of bound K+ for Na+ cations and the concomitant conformational switch was assessed by measuring time-dependent changes in the circular dichroism spectrum accompanying the cation exchange reaction. The time course of these changes was found to consist of three distinct kinetic processes: a rapid phase that was complete in less than 5 ms followed by two slower phases with relaxation times of 40−50 s and 600−800 s at 25 °C and pH 7.0. We interpret these kinetics in terms of a model in which the bound Na+ cations are rapidly replaced by K+ followed by relatively slow structural rearrangements to generate the final K+-bound product(s). Circular dichroism studies showed that addition of the porphyrin TmPyP4 promoted conversion of the basket to the hybrid form. The kinetics of the TmPyP4-induced conformational change were the same as those observed for the cation exchange reaction.
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