THE STRUCTURE OF DAPI BOUND TO DNA
THE STRUCTURE OF DAPI BOUND TO DNA
复制标题
DOI：
10.1080/07391102.1989.10508505
复制
发表时间：
1989-12-01
影响因子：
4.4
通讯作者：
DICKERSON, RE
中科院分区：
文献类型：
--
作者：
LARSEN, TA;GOODSELL, DS;DICKERSON, RE
采用单晶x射线衍射方法，以2.4 .ANG的分辨率解析了合成B-DNA寡核苷酸C-G-C-G-A-A-T-T-C-G-C-G - g的DNA荧光染料4”-6-二胺-2-苯基吲哚（DAPI）的结构。其结构与单独的天然DNA分子几乎是同构的。当DAPI为1，DNA双螺旋为25个水时，2信号以上2428次反射的残差为21.5%。DAPI将自身沿边缘插入狭窄的小槽中，取代了水合作用的有序脊柱。DAPI和一个水分子一起跨越位于双链中心的四个AT碱基对。吲哚氮与两个中心碱基对的胸腺嘧啶O2原子形成分叉的氢键，如netropsin和Hoechst 33258。这三种药物对B-DNA AT区的偏爱是三个因素的结果：(1) B-DNA AT区的小凹槽比GC区的小凹槽窄，导致扁平的芳香药物环在凹槽壁之间紧密配合；(2)AT区的小凹槽内具有更多的负静电电位，部分原因是沿着凹槽底部没有正电nh2基团；(3)没有相同的鸟嘌呤- nh2基团具有空间优势。从而使药物分子更深地沉入凹槽。凹槽宽度和静电因子是区域性的，并且定义了一段DNA的相对接受性，因为它们在几个连续的碱基对上运行。位阻因子是局部的，从一个碱基对变化到下一个碱基对，因此是微调序列特异性的手段。
The structure of the DNA fluorochrome 4''-6-diamidine-2-phenyl indole (DAPI) bound to the synthetic B-DNA oligonucleotide C-G-C-G-A-A-T-T-C-G-C-G has been solved by single crystal x-ray diffraction methods, at a resolution of 2.4 .ANG.. The structure is nearly isomorphous with that of the native DNA molecule alone. With one DAPI and 25 waters per DNA double helix, the residual errors is 21.5% for the 2428 reflections above the 2-signal level. DAPI inserts itself edgewise into the narrow minor groove, displacing the ordered spine of hydration. DAPI and a single water molecule together span the four AT base pairs at the center of the duplex. The indole nitrogen forms a bifurcated hydrogen bond with the thymine O2 atoms of the two central base pairs, as with netropsin and Hoechst 33258. The preference of all three of these drugs for AT regions of B-DNA is a consequence of three factors: (1) The intrinsically narrower minor groove in AT regions than in GC regions of B-DNA, leading to a snug fit of the flat aromatic drug rings between the walls of the groove, (2) The more negative electrostatic potential within the minor groove in AT regions, attributable in part to the absence of electropositive-NH2 groups along the floor of the groove, and (3) The steric advantage of the absence of those same guanine-NH2 groups, thus permitting the drug molecule to sink deeper into the groove. Groove width and electrostatic factors are regional, and define the relative receptiveness of a section of DNA since they operate over several contiguous base pairs. The steric factor is local, varying from one base pair to the next, and hence is the means of fine-tuning sequence specificity.