CRUK Biomolecular Structure Group, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, WC1N 1AX, London, UK.
Nucleic Acids Res. 2012 May;40(10):4691-700. doi: 10.1093/nar/gks023. Epub 2012 Jan 28.
We report here the 1.62 Å crystal structure of an intramolecular quadruplex DNA formed from a sequence in the promoter region of the c-kit gene. This is the first reported crystal structure of a promoter quadruplex and the first observation of localized magnesium ions in a quadruplex structure. The structure reveals that potassium and magnesium ions have an unexpected yet significant structural role in stabilizing particular quadruplex loops and grooves that is distinct from but in addition to the role of potassium ions in the ion channel at the centre of all quadruplex structures. The analysis also shows how ions cluster together with structured water molecules to stabilize the quadruplex arrangement. This particular quadruplex has been previously studied by NMR methods, and the present X-ray structure is in accord with the earlier topology assignment. However, as well as the observations of potassium and magnesium ions, the crystal structure has revealed a highly significant difference in the dimensions of the large cleft in the structure, which is a plausible target for small molecules. This difference can be understood by the stabilizing role of structured water networks.
我们在此报告了一个来自 c-kit 基因启动子区域的序列形成的分子内四链体 DNA 的 1.62Å 晶体结构。这是第一个报道的启动子四链体的晶体结构，也是第一个观察到局部镁离子存在于四链体结构中的例子。该结构揭示了钾离子和镁离子在稳定特定四链体环和沟方面具有出人意料但又非常重要的结构作用，这种作用不同于但又补充了钾离子在所有四链体结构中心的离子通道中的作用。分析还表明离子如何与结构水分子一起聚集以稳定四链体排列。这个特殊的四链体以前已经通过 NMR 方法进行了研究，目前的 X 射线结构与早期的拓扑分配一致。然而，除了钾离子和镁离子的观察结果外，晶体结构还揭示了结构中大裂缝尺寸的一个非常显著的差异，这是小分子的一个合理靶点。这种差异可以通过结构水分子网络的稳定作用来理解。
