Gill Michelle L, Strobel Scott A, Loria J Patrick
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
J Am Chem Soc. 2005 Nov 30;127(47):16723-32. doi: 10.1021/ja055358f.
Monovalent cations play an important role in many biological functions. The guanine rich sequence, d(G4T4G4), requires monovalent cations for formation of the G-quadruplex, d(G4T4G4)2. This requirement can be satisfied by thallium (Tl+), a potassium (K+) surrogate. To verify that the structure of d(G4T4G4)2 in the presence of Tl+ is similar to the K+-form of the G-quadruplex, the solution structure of the Tl+-form of d(G4T4G4)2 was determined. The 10 lowest energy structures have an all atom RMSD of 0.76 +/- 0.16 A. Comparison of this structure to the identical G-quadruplex formed in the presence of K+ validates the isomorphous nature of Tl+ and K+. Using a 1H-205Tl spin-echo difference experiment we show that, in the Tl+-form of d(G4T4G4)2, small scalar couplings (<1 Hz) exist between 205Tl and protons in the G-quadruplex. These data comprise the first 1H-205Tl scalar couplings observed in a biological system and have the potential to provide important constraints for structure determination. These experiments can be applied to any system in which the substituted Tl+ cations are in slow exchange with the bulk ions in solution.
单价阳离子在许多生物学功能中发挥着重要作用。富含鸟嘌呤的序列d(G4T4G4)形成G-四链体d(G4T4G4)2需要单价阳离子。铊（Tl+）作为钾（K+）的替代物可以满足这一需求。为了验证在存在Tl+的情况下d(G4T4G4)2的结构是否与G-四链体的K+形式相似，我们测定了d(G4T4G4)2的Tl+形式的溶液结构。能量最低的10种结构的全原子均方根偏差为0.76±0.16 Å。将该结构与在存在K+的情况下形成的相同G-四链体进行比较，证实了Tl+和K+的同构性质。通过1H-205Tl自旋回波差异实验，我们表明，在d(G4T4G4)2的Tl+形式中，G-四链体中的205Tl与质子之间存在小的标量耦合（<1 Hz）。这些数据是在生物系统中观察到的首批1H-205Tl标量耦合，有可能为结构测定提供重要约束。这些实验可应用于任何被取代的Tl+阳离子与溶液中的大量离子进行缓慢交换的系统。
