Department of Biology and Interuniversity Consortium, National Institute Biostructure and Biosystem, University of Rome Tor Vergata, Rome, Italy.
PLoS One. 2013 Jul 2;8(7):e68404. doi: 10.1371/journal.pone.0068404. Print 2013.
A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme, but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples a conformational space much larger than the corresponding domain in the human enzyme. The large linker conformational variability is then linked to important functional properties such as an increased religation rate and a low drug reactivity, demonstrating that the linker domain has a crucial role in the modulation of the topoisomerase IB activity.
一种人/疟原虫杂种酶，通过将人拓扑异构酶 IB 连接域与疟原虫 falciparum 酶的相应结构域交换而产生并进行了特性分析。杂种酶显示出与人类酶相当的松弛活性，但它的重新连接速率要快得多。杂种酶也对喜树碱具有抗性。杂种酶的三维结构已经建立，并通过分子动力学模拟对其结构-动力学特性进行了分析。分析表明，交换的疟原虫连接子可以采样比人酶中相应结构域更大的构象空间。较大的连接子构象可变性与重要的功能特性相关，例如增加的重新连接率和低药物反应性，表明连接子结构域在拓扑异构酶 IB 活性的调节中起着关键作用。
