Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131, Padua, Italy.
Cell Mol Life Sci. 2010 Jun;67(12):2001-24. doi: 10.1007/s00018-010-0299-5. Epub 2010 Feb 18.
Topoisomerases are vital enzymes specialized in controlling DNA topology, in particular supercoiling and decatenation, to properly handle nucleic acid packing and cell dynamics. The type IIA enzymes act by cleaving both strands of a double helix and having another strand from the same or another molecule cross the DNA gate before a re-sealing event completes the catalytic cycle. Here, we will consider the two types of IIA prokaryotic topoisomerases, DNA Gyrase and Topoisomerase IV, as crucial regulators of bacterial cell cycle progression. Their synergistic action allows control of chromosome packing and grants occurrence of functional transcription and replication processes. In addition to displaying a fascinating molecular mechanism of action, which transduces chemical energy into mechanical energy by means of large conformational changes, these enzymes represent attractive pharmacological targets for antibacterial chemotherapy.
拓扑异构酶是一类专门控制 DNA 拓扑结构的重要酶，特别是超螺旋和解连环，以正确处理核酸包装和细胞动力学。IIA 型酶通过切割双链 DNA 并使来自同一分子或另一个分子的另一条链穿过 DNA 门，然后在重新封闭事件完成催化循环之前，发挥作用。在这里，我们将考虑两种类型的 IIA 原核拓扑异构酶，DNA 回旋酶和拓扑异构酶 IV，作为细菌细胞周期进展的关键调节剂。它们的协同作用允许控制染色体包装，并赋予功能转录和复制过程的发生。除了表现出一种迷人的分子作用机制，即通过大构象变化将化学能量转化为机械能之外，这些酶还代表了抗菌化疗的有吸引力的药理靶标。
