Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein-DNA binding site.
Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein-DNA binding site.
复制标题
DOI：
10.1093/nar/gku654
复制
发表时间：
2014-08
影响因子：
14.9
通讯作者：
Desideri A
中科院分区：
文献类型：
--
作者：
D'Annessa I;Coletta A;Sutthibutpong T;Mitchell J;Chillemi G;Harris S;Desideri A
人拓扑异构酶1B已被模拟共价结合到负超螺旋DNA微环，并将其行为与结合到简单线性DNA双链体的酶进行比较。与简单的线性双链体片段相比，更真实的超螺旋底物的存在促进了大量蛋白质-DNA相互作用的形成。蛋白质-DNA氢键的数量在接近活性位点处加倍，影响催化五元组中的所有残基。在DNA上的钳位，其特征在于Lys 369和Glu 497之间的盐桥，当与超螺旋微环结合时经历减少的波动。的酶，这是在超螺旋应力的控制松弛牵连的接头结构域，也显示出与微环相比，线性DNA的接触数量增加。最后，超螺旋DNA微环的更复杂的拓扑结构产生了二级DNA结合位点，涉及位于亚结构域III上的四个残基。的模拟轨迹揭示了显着的变化，酶和DNA之间的相互作用，更复杂的DNA拓扑结构，这是一致的实验观察，蛋白质有一个偏好结合超螺旋DNA。
Human topoisomerase 1B has been simulated covalently bound to a negatively supercoiled DNA minicircle, and its behavior compared to the enzyme bound to a simple linear DNA duplex. The presence of the more realistic supercoiled substrate facilitates the formation of larger number of protein–DNA interactions when compared to a simple linear duplex fragment. The number of protein–DNA hydrogen bonds doubles in proximity to the active site, affecting all of the residues in the catalytic pentad. The clamp over the DNA, characterized by the salt bridge between Lys369 and Glu497, undergoes reduced fluctuations when bound to the supercoiled minicircle. The linker domain of the enzyme, which is implicated in the controlled relaxation of superhelical stress, also displays an increased number of contacts with the minicircle compared to linear DNA. Finally, the more complex topology of the supercoiled DNA minicircle gives rise to a secondary DNA binding site involving four residues located on subdomain III. The simulation trajectories reveal significant changes in the interactions between the enzyme and the DNA for the more complex DNA topology, which are consistent with the experimental observation that the protein has a preference for binding to supercoiled DNA.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
人拓扑异构酶I中的THR729通过改变蛋白质结构域的通信来调节抗癌耐药性，如分子动力学模拟所建议的那样。
影响因子：
14.9
作者：
Chillemi, Giovanni;D'Annessa, Ilda;Fiorani, Paola;Losasso, Carmen;Benedetti, Piero;Desideri, Alessandro
通讯作者：
Desideri, Alessandro
影响因子：
14.9
作者：
Lavery R;Moakher M;Maddocks JH;Petkeviciute D;Zakrzewska K
通讯作者：
Zakrzewska K
DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.6
作者：
Mitchell, Jonathan S.;Harris, Sarah A.
通讯作者：
Harris, Sarah A.