| 张靖雲,杨爱江,胡霞,姚琴,岑忠倩,孙瑗忆,李慈兴.化学通报,2024,87(12):1428-1437. |
| Sb3+与小牛胸腺DNA的相互作用及驱动机制 |
| The Interaction and Driving Mechanism between Sb3+ And Calf Thymus DNA |
| 投稿时间：2024-07-18 修订日期：2024-08-21 |
| DOI： |
| 中文关键词: 锑 小牛胸腺DNA 遗传毒性 沟槽结合 分子动力学 |
| 英文关键词:Antimony, ctDNA, Genetoxic, Groove mode, Molecular Dynamics |
| 基金项目:贵州省教育厅科技创新团队项目(黔教基[2023]056)和贵州大学科研创新团队项目(贵大科创团[2023]05号)资助 |
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| 中文摘要: |
| 锑（Antimony，Sb）是一种常见的污染物，其在环境中常以Sb3+和Sb5+的形态存在。Sb3+毒性较Sb5+更强，且会对多种生物的DNA造成损伤，但其与DNA的直接结合模式和结合驱动机制并不清楚。本研究通过多光谱学（包括紫外吸收光谱、荧光竞争取代、圆二色谱分析等）结合分子动力学（MD）技术，详细测定了Sb3+与DNA的相互作用。结果表明，Sb3+通过沟槽模式与DNA结合，对DNA的粘度、变性温度及结构产生了轻微影响。根据热力学规律，Sb3+与DNA的结合主要受静电作用力驱动，Sb3+-DNA复合物荧光淬灭机制为静态淬灭，存在至少一个结合位点，结合常数达约为104 M-1，显著高于大多数碱土金属。MD模拟验证了上述实验结果，展示了Sb3+能够稳定结合在DNA小沟槽的G-C碱基富集区，平均距离为2.4 ?。在整个MD过程中，静电作用的存在时间均大于98%，均方根偏差（RMSD）保持在3.5 A以下，DNA的二级蛋白结构域并未发生严重破坏。本研究揭示了Sb3?与DNA直接相互作用的机制，为其有害作用研究及抑制手段提供了科学依据。 |
| 英文摘要: |
| Antimony (Sb) is a common pollutant found in the environment in the forms of Sb3+ and Sb5+. Sb3+ is more toxic than Sb5+ and has been shown to cause DNA damage in various organisms. However, the precise binding mode of Sb3+ to DNA and the driving mechanism of this binding remain unclear. This study utilized multispectroscopy techniques, such as UV absorption spectroscopy, fluorescence competitive substitution, and circular dichroism analysis, along with molecular dynamics (MD) simulations, to investigate the interaction between Sb3+ and DNA. The findings revealed that Sb3+ binds to DNA through a groove mode, leading to slight changes in DNA viscosity, denaturation temperature, and structure. The thermodynamic analysis indicated that electrostatic forces primarily drive the binding of Sb3+ to DNA. The fluorescence quenching mechanism of the Sb3+-DNA complex was identified as static quenching, with a binding constant of approximately 104 M-1, significantly higher than that of most alkaline-earth metals. MD simulations confirmed the experimental results, showing stable binding of Sb3+ to the G-C base-rich region of the DNA groove, with an average distance of 2.0 ?. Throughout the simulation, electrostatic interactions were present over 98% of the time, the root mean square deviation (RMSD) remained below 3.5 ?, and the secondary protein structural domains of DNA were minimally affected. This study elucidates the direct interaction mechanism of Sb3+ with DNA, providing a scientific foundation for understanding its harmful effects and potential inhibition strategies. |
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