Structures of minimal catalytic fragments of topoisomerase V reveals conformational changes relevant for DNA binding.
Structures of minimal catalytic fragments of topoisomerase V reveals conformational changes relevant for DNA binding.
复制标题
拓扑异构酶 V 最小催化片段的结构揭示了与 DNA 结合相关的构象变化。
DOI：
10.1016/j.str.2010.03.006
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Mondragon,Alfonso
中科院分区：
文献类型：
--
作者：
Rajan,Rakhi;Taneja,Bhupesh;Mondragon,Alfonso
拓扑异构酶V是一种古细菌I型拓扑异构酶，由于在同一蛋白质中存在拓扑异构酶和DNA修复活性，其在拓扑异构酶中是独特的。它被组织为N-末端拓扑异构酶结构域，随后是24个串联螺旋-发夹-螺旋（HhH）基序。结构研究表明，活性位点被（HhH）基序掩埋。在这里，我们表明，N-末端结构域可以放松DNA在没有任何HHH基序和HHH基序是所需的稳定的蛋白质-DNA复合物的形成。各种拓扑异构酶V片段的晶体结构显示由长弯曲接头螺旋介导的结构域的相对取向的变化，并且这些运动对于DNA进入活性位点是必不可少的。磷酸根离子结合到蛋白质的活性位点附近，有助于在拓扑异构酶结构域中模拟DNA，并显示拓扑异构酶V如何与DNA相互作用。
Topoisomerase V is an archaeal type I topoisomerase that is unique among topoisomerases due to presence of both topoisomerase and DNA repair activities in the same protein. It is organized as an N-terminal topoisomerase domain followed by 24 tandem helix-hairpin-helix (HhH) motifs. Structural studies have shown that the active site is buried by the (HhH) motifs. Here we show that the N-terminal domain can relax DNA in the absence of any HhH motifs and that the HhH motifs are required for stable protein-DNA complex formation. Crystal structures of various topoisomerase V fragments show changes in the relative orientation of the domains mediated by a long bent linker helix, and these movements are essential for the DNA to enter the active site. Phosphate ions bound to the protein near the active site helped model DNA in the topoisomerase domain and show how topoisomerase V may interact with DNA.