Bush Natassja G, Evans-Roberts Katherine, Maxwell Anthony
EcoSal Plus. 2015;6(2). doi: 10.1128/ecosalplus.ESP-0010-2014.
DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils into DNA. Because of their essentiality in all cells and the fact that their reactions proceed via DNA breaks, topoisomerases have become important drug targets; the bacterial enzymes are key targets for antibacterial agents. This article discusses the structure and mechanism of topoisomerases and their roles in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors, including antibiotics in clinical use, is also discussed.
DNA拓扑异构酶是控制所有细胞中DNA拓扑结构的酶。有I型和II型两种类型,根据它们是否在DNA中产生瞬时单链或双链断裂来分类。它们的反应通常涉及DNA的单链或双链片段通过这种瞬时断裂,并由DNA - 蛋白质共价键稳定。所有拓扑异构酶都可以使DNA松弛,但存在于所有细菌中的DNA促旋酶也可以将超螺旋引入DNA。由于它们在所有细胞中的重要性以及它们的反应通过DNA断裂进行这一事实,拓扑异构酶已成为重要的药物靶点;细菌的拓扑异构酶是抗菌剂的关键靶点。本文讨论了拓扑异构酶的结构和机制及其在细菌细胞中的作用。还讨论了包括临床使用的抗生素在内的抑制剂对细菌拓扑异构酶的靶向作用。