Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.
UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
Nucleic Acids Res. 2021 Jan 11;49(1):519-528. doi: 10.1093/nar/gkaa1177.
Quadruplex DNAs can fold into a variety of distinct topologies, depending in part on loop types and orientations of individual strands, as shown by high-resolution crystal and NMR structures. Crystal structures also show associated water molecules. We report here on an analysis of the hydration arrangements around selected folded quadruplex DNAs, which has revealed several prominent features that re-occur in related structures. Many of the primary-sphere water molecules are found in the grooves and loop regions of these structures. At least one groove in anti-parallel and hybrid quadruplex structures is long and narrow and contains an extensive spine of linked primary-sphere water molecules. This spine is analogous to but fundamentally distinct from the well-characterized spine observed in the minor groove of A/T-rich duplex DNA, in that every water molecule in the continuous quadruplex spines makes a direct hydrogen bond contact with groove atoms, principally phosphate oxygen atoms lining groove walls and guanine base nitrogen atoms on the groove floor. By contrast, parallel quadruplexes do not have extended grooves, but primary-sphere water molecules still cluster in them and are especially associated with the loops, helping to stabilize loop conformations.
四链体 DNA 可以折叠成多种不同的拓扑结构，这部分取决于单链的环类型和取向，如高分辨率晶体和 NMR 结构所示。晶体结构还显示了相关的水分子。我们在此报告了对选定折叠四链体 DNA 周围水合排列的分析，这揭示了在相关结构中反复出现的几个突出特征。许多初级球水分子存在于这些结构的沟槽和环区。在反平行和混合四链体结构中，至少有一个沟槽又长又窄，包含大量连接的初级球水分子的脊柱。这个脊柱类似于但从根本上不同于在富含 A/T 的双链 DNA 小沟中观察到的特征性脊柱，因为连续四链体脊柱中的每个水分子都与沟原子（主要是沟壁的磷酸氧原子和沟底的鸟嘌呤碱基氮原子）直接形成氢键接触。相比之下，平行四链体没有延伸的沟槽，但初级球水分子仍然聚集在其中，特别是与环有关，有助于稳定环构象。
