Structural insights into the function of type IB topoisomerases
Structural insights into the function of type IB topoisomerases
复制标题
DOI：
10.1016/s0959-440x(99)80005-0
复制
发表时间：
1999-02-01
影响因子：
6.8
通讯作者：
Hol, Wim G.J.
中科院分区：
文献类型：
--
作者：
Redinbo, Matthew R.;Champoux, James J.;Hol, Wim G.J.
拓扑异构酶可放松细胞中由于转录、复制和重组等多种核过程而产生的 DNA 超螺旋张力。最近确定的人拓扑异构酶 I 与 DNA 复合物以及痘苗病毒拓扑异构酶 27 kDa 催化结构域的晶体结构增进了我们对真核 IB 型拓扑异构酶的理解。这些最近的结构结果提供了对这些拓扑异构酶功能方面的见解，包括它们的 DNA 结合、链裂解和再连接活性，以及这些酶用来放松 DNA 超螺旋张力的机制。此外，两个拟议的抗癌药物喜树碱与人类拓扑异构酶 I 和 DNA 共价复合物结合的模型表明了该药物作用模式的结构基础。
Topoisomerases relax the DNA superhelical tension that arises in cells as a result of several nuclear processes, including transcription, replication and recombination. Recently determined crystal structures of human topoisomerase I in complex with DNA and of the 27 kDa catalytic domain of the vaccinia virus topoisomerase have advanced our understanding of the eukaryotic type IB topoisomerases. These recent structural results provide insights into functional aspects of these topoisomerases, including their DNA binding, strand cleavage and religation activities, as well as the mechanism that these enzymes use to relax DNA superhelical tension. In addition, two proposed models of the anticancer drug camptothecin bound to a covalent complex of human topoisomerase I and DNA suggest a structural basis for the mode of action of the drug.