Gao Y G, Robinson H, van Boom J H, Wang A H
Division of Biophysics, University of Illinois at Urbana-Champaign 61801, USA.
Biophys J. 1995 Aug;69(2):559-68. doi: 10.1016/S0006-3495(95)79929-5.
A-DNA is a stable alternative right-handed double helix that is favored by certain sequences (e.g., (dG)n.(dC)n) or under low humidity conditions. Earlier A-DNA structures of several DNA oligonucleotides and RNA.DNA chimeras have revealed some conformational variation that may be the result of sequence-dependent effects or crystal packing forces. In this study, four crystal structures of three decamer oligonucleotides, d(ACCGGCCGGT), d(ACCCGCGGGT), and r(GC)d(GTATACGC) in two crystal forms (either the P6(1)22 or the P2(1)2(1)2(1) space group) have been analyzed at high resolution to provide the molecular basis of the structural difference in an experimentally consistent manner. The study reveals that molecules crystallized in the same space group have a more similar A-DNA conformation, whereas the same molecule crystallized in different space groups has different (local) conformations. This suggests that even though the local structure is influenced by the crystal packing environments, the DNA molecule adjusts to adopt an overall conformation close to canonical A-DNA. For example, the six independent CpG steps in these four structures have different base-base stacking patterns, with their helical twist angles (omega) ranging from 28 degrees to 37 degrees. Our study further reveals the structural impact of different counter-ions on the A-DNA conformers. [Co(NH3)6]3+ has three unique A-DNA binding modes. One binds at the major groove side of a GpG step at the O6/N7 sites of guanine bases via hydrogen bonds. The other two modes involve the binding of ions to phosphates, either bridging across the narrow major groove or binding between two intra-strand adjacent phosphates. Those interactions may explain the recent spectroscopic and NMR observations that [Co(NH3)6]3+ is effective in inducing the B- to A-DNA transition for DNA with (G)n sequence. Interestingly, Ba2+ binds to the same O6/N7 sites on guanine by direct coordinations.
A-DNA是一种稳定的右手双螺旋结构，在某些序列（如(dG)n.(dC)n）或低湿度条件下更易形成。此前对几种DNA寡核苷酸和RNA-DNA嵌合体的A-DNA结构研究揭示了一些构象变化，这些变化可能是序列依赖性效应或晶体堆积力的结果。在本研究中，对三种十聚体寡核苷酸d(ACCGGCCGGT)、d(ACCCGCGGGT)和r(GC)d(GTATACGC)在两种晶体形式（P6(1)22或P2(1)2(1)2(1)空间群）下的四个晶体结构进行了高分辨率分析，以实验一致的方式提供结构差异的分子基础。研究表明，在相同空间群中结晶的分子具有更相似的A-DNA构象，而在不同空间群中结晶的同一分子具有不同的（局部）构象。这表明，尽管局部结构受晶体堆积环境影响，但DNA分子会进行调整以采用接近标准A-DNA的整体构象。例如，这四个结构中的六个独立的CpG步骤具有不同的碱基堆积模式，其螺旋扭转角（ω）范围为28度至37度。我们的研究进一步揭示了不同抗衡离子对A-DNA构象体的结构影响。[Co(NH3)6]3+具有三种独特的A-DNA结合模式。一种通过氢键在鸟嘌呤碱基的O6/N7位点处的GpG步骤的大沟侧结合。另外两种模式涉及离子与磷酸根的结合，要么横跨狭窄的大沟桥连，要么在两条链内相邻磷酸根之间结合。这些相互作用可能解释了最近的光谱和核磁共振观察结果，即[Co(NH3)6]3+对具有(G)n序列的DNA诱导B型到A型的转变有效。有趣的是，Ba2+通过直接配位作用与鸟嘌呤上相同的O6/N7位点结合。
