Structure and hydration of the DNA-Human topoisomerase I covalent complex
Structure and hydration of the DNA-Human topoisomerase I covalent complex
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DOI：
10.1016/s0006-3495(01)75716-5
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发表时间：
2001-07-01
影响因子：
3.4
通讯作者：
Desideri, A
中科院分区：
文献类型：
--
作者：
Chillemi, G;Castrignanò, T;Desideri, A
用分子动力学模拟方法研究了重组人拓扑异构酶I的结构和水化作用，该酶由核心区和羧基末端结构域组成的22碱基DNA双链共价复合体组成。在模拟过程中，发现结构和分子间相互作用保持得很好。该复合体显示了接触区域的高度灵活性，大量水介导的蛋白质-DNA氢键的存在证实了这一点，在数量和分布上与直接氢键相当。酶和溶剂之间的相互作用也为解释单一残基突变时观察到的活性或亲和力的实验降低提供了关键。最后，在活性中心附近观察到四个持久的水分子，其中一个处于合适的位置，可以接受来自活性Tyr723的质子。
The structure and hydration of reconstituted human topoisomerase I comprising the core and the carboxyl-terminal domains in covalent complex with 22-basepair DNA duplex has been investigated by molecular dynamics simulation. The structure and the intermolecular interactions were found to be well maintained over the simulation. The complex displays a high degree of flexibility of the contact area, confirmed by the presence of numerous water-mediated protein-DNA hydrogen bonds comparable in quantity and distribution to the direct ones. The interaction between the enzyme and the solvent also provides the key for interpreting the experimental reduction of activity or affinity observed upon single residue mutation. Finally, four long lasting water molecules are observed in the proximity of the active site, one of which in the appropriate position to accept a proton from the active Tyr723.