Toward a designed, functioning genetic system with expanded-size base pairs: Solution structure of the eight-base xDNA double helix
Toward a designed, functioning genetic system with expanded-size base pairs: Solution structure of the eight-base xDNA double helix
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DOI：
10.1021/ja065606n
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发表时间：
2006-11-15
影响因子：
15
通讯作者：
Kool, Eric T.
中科院分区：
文献类型：
--
作者：
Lynch, Stephen R.;Liu, Haibo;Kool, Eric T.
我们描述了NMR衍生的解决方案结构的双螺旋形式的一个设计的八个碱基的遗传配对系统，称为xDNA。苯并同源xDNA设计含有比天然DNA对宽约100倍的碱基对。2.4埃（苯环的宽度）。该xDNA螺旋的八个组成碱基是A、C、G、T、xA、xT、xC和xG。在水缓冲液中使用一维和二维NMR方法结合约束分子动力学来解决结构。数据表明，十聚体双链体是右手的和反平行的，并且以类似于沃森-克里克DNA的方式氢键合。糖-磷酸骨架采用与B型DNA相似的规则构象，由于螺旋的周长较大，二面角调整较小。这些凹槽比B型DNA的凹槽更宽更浅，螺旋转动更慢，约为100 °。每360度旋转12个碱基对。存在广泛的链内和链间碱基堆积表面积，为xDNA相对于天然DNA的更大稳定性提供了解释。也有证据表明，更大的运动在这个结构相比，以前的两个基地扩大螺旋，可能的化学和结构原因进行了讨论。结果证实了所设计的xDNA系统的配对自组装。这表明，除了自然结构之外，其他遗传系统结构可能在编码信息并将其转移到新的互补链中发挥作用。
We describe the NMR-derived solution structure of the double-helical form of a designed eight-base genetic pairing system, termed xDNA. The benzo-homologous xDNA design contains base pairs that are wider than natural DNA pairs by ca. 2.4 angstrom (the width of a benzene ring). The eight component bases of this xDNA helix are A, C, G, T, xA, xT, xC, and xG. The structure was solved in aqueous buffer using 1D and 2D NMR methods combined with restrained molecular dynamics. The data show that the decamer duplex is right-handed and antiparallel, and hydrogen-bonded in a way analogous to that of Watson-Crick DNA. The sugar-phosphate backbone adopts a regular conformation similar to that of B-form DNA, with small dihedral adjustments due to the larger circumference of the helix. The grooves are much wider and more shallow than those of B-form DNA, and the helix turn is slower, with ca. 12 base pairs per 360 degrees turn. There is an extensive intra-and interstrand base stacking surface area, providing an explanation for the greater stability of xDNA relative to natural DNA. There is also evidence for greater motion in this structure compared to a previous two-base-expanded helix; possible chemical and structural reasons for this are discussed. The results confirm paired self-assembly of the designed xDNA system. This suggests the possibility that other genetic system structures besides the natural one might be functional in encoding information and transferring it to new complementary strands.