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首页> 外文期刊>Biophysical Journal >Local DNA Base Conformations and Ligand Intercalation in DNA Constructs Containing Optical Probes
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Local DNA Base Conformations and Ligand Intercalation in DNA Constructs Containing Optical Probes

机译：含有光学探针的DNA构建体中的局部DNA基础构象和配体嵌段

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摘要

Understanding local conformations of DNA at the level of individual nucleic acid bases and base pairs is important for elucidating molecular processes that depend on DNA sequence. Here, we apply linear absorption and circular dichroism measurements to the study of local DNA conformations, using the guanine base analog 6-methyl isoxanthopterin (6-MI) as a structural probe. We show that the spectroscopic properties of this probe can provide detailed information about the average local base and basepair conformations as a function of the surrounding DNA sequence. Based on these results we apply a simple theoretical model to calculate the circular dichroism spectra of 6-MI-substituted DNA constructs and show that our model can be used to extract information about how the local conformations of the 6-MI probe are influenced by the local base or basepair environment. We also use this probe to examine the pathway for the insertion (intercalation) of a tethered acridine ligand (9-amino-6-chloro methoxyacridine) into duplex DNA. We show that this model intercalator interacts with duplex DNA by a "displacement insertion intercalation" mechanism, whereby the acridine moiety is inserted into the DNA structure and displaces the base located opposite its attachment site. These findings suggest that site-specifically positioned base analog probes can be used to characterize the molecular and structural details of binding ligand effects on local base stacking and unstacking reactions in single- and double-stranded DNA and thus may help to define the molecular mechanisms of DNA-protein interactions that involve the site-specific intercalation of aromatic amino acid side chains into genomic DNA.
机译：理解单个核酸碱和碱基对DNA的局部构象对于阐明依赖于DNA序列的分子过程非常重要。这里，我们将线性吸收和圆形二色性测量应用于局部DNA构象的研究，使用鸟嘌呤基础类似物6-甲基异体（6-MI）作为结构探针。我们表明该探针的光谱性能可以提供关于平均局部基础和基础大气构象的详细信息，作为周围的DNA序列的函数。基于这些结果，我们应用一个简单的理论模型来计算6-MI-取代的DNA构建体的圆形二色体谱，并表明我们的模型可用于提取关于6-MI探针的局部构象的信息受到影响的影响本地基地或基座环境。我们还使用该探针检查将吖啶吖啶配体（9-氨基-6-氯甲氧基丙啶）的插入（嵌入）插入（嵌入）中的途径中的双相DNA。我们表明该模型嵌入剂通过“位移插入嵌入”机构与双相DNA相互作用，由此吖啶部分插入DNA结构中并将位于其附接部位相对的底座上插入。这些发现表明，特异性定位的基础模拟探针可用于表征对局部基础堆叠和单链和双链DNA中的局部基础堆叠和未堆积反应的分子和结构细节，从而有助于定义分子机制DNA-蛋白质相互作用涉及芳族氨基酸侧链的位点特异性嵌入到基因组DNA中。

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  • 来源
    《Biophysical Journal》 |2019年第6期|共15页
  • 作者

    Ji Huiying; Johnson Neil P.; von Hippel Peter H.; Marcus Andrew H.;

  • 作者单位

    Univ Oregon Dept Chem &

    Biochem Ctr Opt Mol &

    Quantum Sci Eugene OR 97403 USA;

    Univ Oregon Dept Chem &

    Biochem Inst Mol Biol Eugene OR 97403 USA;

    Univ Oregon Dept Chem &

    Biochem Inst Mol Biol Eugene OR 97403 USA;

    Univ Oregon Dept Chem &

    Biochem Ctr Opt Mol &

    Quantum Sci Eugene OR 97403 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物物理学;
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