Variability in DNA minor groove width recognised by ligand binding: the crystal structure of a bis-benzimidazole compound bound to the DNA duplex d(CGCGAATTCGCG)2.
Variability in DNA minor groove width recognised by ligand binding: the crystal structure of a bis-benzimidazole compound bound to the DNA duplex d(CGCGAATTCGCG)2.
复制标题
通过配体结合识别的 DNA 小沟宽度的变化：与 DNA 双链体 d(CGCGAATTCGCG)2 结合的双苯并咪唑化合物的晶体结构。
DOI：
10.1093/nar/23.18.3678
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发表时间：
1995
影响因子：
14.9
通讯作者：
Neidle,S
中科院分区：
文献类型：
--
作者：
Wood,AA;Nunn,CM;Czarny,A;Boykin,DW;Neidle,S
DNA结合化合物Hoechst 33258的类似物，其中哌嗪环已被咪唑啉基团取代，已与十二核苷酸序列d（CGCGAATTCGCG）2共结晶。通过X射线衍射分析解决了结构，并在2.0 μ m的分辨率下精确到19.7%的R因子。配体结合在B-DNA双螺旋的小沟中，在中心的四个AATT碱基对处，涉及许多货车德瓦耳斯接触和氢键。两种化合物在沿着大部分AATT区域的小沟宽度上存在显著差异。特别地，与Hoechst 33258的哌嗪环相比，该结构在结合位点的3′端显示出与咪唑基团的较窄横截面一致的较窄凹槽，因此凹槽宽度的扰动较小。与Hoechst 33258本身相比，该类似物对DNA的结合亲和力更高，已根据这些差异进行了合理化。
An analogue of the DNA-binding compound Hoechst 33258, in which the piperazine ring has been replaced by an imidazoline group, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)2. The structure has been solved by X-ray diffraction analysis and has been refined to an R-factor of 19.7% at a resolution of 2.0 Å. The ligand is found to bind in the minor groove, at the central four AATT base pairs of the B-DNA double helix, with the Involvement of a number of van der Waals contacts and hydrogen bonds. There are significant differences in minor groove width for the two compounds, along much of the AATT region. in particular this structure shows a narrower groove at the 3′ end of the binding site consistent with the narrower cross-section of the imidazole group compared with the piperazine ring of Hoechst 33258 and therefore a smaller perturbation in groove width. The higher binding affinity to DNA shown by this analogue compared with Hoechst 33258 itself, has been rationalised in terms of these differences.