高等学校化学学报

高等学校化学学报

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分子动力学研究亚铁血红素激活蛋白转录激活机理

赵熹, 黄旭日, 孙家锺   

  1. 吉林大学理论化学研究所, 理论化学计算国家重点实验室, 长春 130023
  • 收稿日期:2007-01-31 修回日期:1900-01-01 出版日期:2008-04-10 发布日期:2008-04-10
  • 通讯作者: 黄旭日

Molecular Dynamics Study of Transcriptional Activation Mechanism of Heme Activator Protein

ZHAO Xi, HUANG Xu-Ri*, SUN Chia-Chung   

  1. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China
  • Received:2007-01-31 Revised:1900-01-01 Online:2008-04-10 Published:2008-04-10
  • Contact: HUANG Xu-Ri

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被引次数

8

摘要： 以3种亚铁血红素激活蛋白(Heme activator protein, HAP)-DNA 复合物(野生型HAP1-wt, Ser63/Arg63突变HAP1-18 和 Ser63/Gly63突变HAP1-PC7)为对象对亚铁血红素激活蛋白的转录激活机理进行了分子动力学研究. 对3个复合物分子动力学轨迹的比较性分析显示, 涉及到上游活化序列(Upstream activation sequences, UAS)识别的蛋白质-DNA 相互作用分布与实验观测到的3种蛋白转录活性一致. 进一步对3个复合物进行柔性分析显示, 3个DNA分子具有相似的柔性, 而又有所不同, 特别在涉及UAS识别的N-端和Zn2Cys6结构域前部有明显的柔性差异. 蛋白质柔性的差别导致不同的蛋白质-DNA相互作用. 因此亚铁血红素激活蛋白的N-端和Zn2Cys6结构域前部的柔性大小能够调节亚铁血红素激活蛋白转录激活功能.

关键词: 分子动力学, 转录激活, 柔性, 亚铁血红素激活蛋白

Abstract: A molecular dynamics(MD) simulations for three kinds of protein(heme activator protein: HAP)-DNA complexes crystal structures were performed: the HAP1-wt, two HAP1 mutants(HAP1-PC7: Ser63/Gly63; HAP1-18: Ser63/Arg63) with the aim of investigating the mechanism of HAP transcriptional activation. Comparative analyses of MD structures for the three HAP-DNA complexes reveal that the key protein-DNA interactions involving the recognization of UAS i.e CGC are different in three complexes as the experimental observations. Further analyses reveal that three HAPs exhibit different flexibilities, relative to very similar conformations of three bound DNA. It is found that the difference of flexibilities in three HAPs results in diversities in conformations of N-term Arm and Zn2Cys6 Binuclear Cluster involving DNA recognition, causing varieties of protein-DNA interactions. According to these results, the flexibility of N-term and Zn2Cys6 Binuclear Cluster in HAP can play a crucial role in regulating transcriptional activation, which can directly lead to the alternative protein-DNA interactions.

Key words: Molecular dynamics, Transcriptional activation, Flexibility, Heme activator protein

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