Type IA Topoisomerases as Targets for Infectious Disease Treatments.
Type IA Topoisomerases as Targets for Infectious Disease Treatments.
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DOI：
10.3390/microorganisms9010086
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发表时间：
2021-01-01
期刊：
影响因子：
4.5
通讯作者：
Tse-Dinh YC
中科院分区：
文献类型：
--
作者：
Seddek A;Annamalai T;Tse-Dinh YC
传染病是全世界死亡的主要原因之一，抗菌素耐药性是一个巨大的挑战。需要开发新的抗生素以提供治疗性治疗选择，需要确定和追求新的药物靶点。DNA拓扑异构酶通过与DNA链通过偶联的DNA切割-重新连接来控制DNA的拓扑结构。DNA拓扑结构的改变必须在DNA复制、转录和修复等重要过程中得到控制。IIA型拓扑异构酶是抗生素的公认靶标。在这篇综述中，细菌中的IA型拓扑异构酶被讨论为新抗生素的潜在靶点。在某些细菌病原体中，拓扑异构酶I是唯一存在的IA型拓扑异构酶，这使其成为有价值的抗生素靶标。这篇综述将总结最近的尝试，已确定抑制剂的细菌拓扑异构酶I作为潜在的线索抗生素和使用这些抑制剂作为分子探针在细胞研究。生物素-酶复合物的晶体结构及其作用机制的更深入了解将有助于建立潜在药物先导物的结构-活性关系，并开发有效和选择性的治疗方法，有助于对抗威胁公共卫生的耐药细菌感染。
Infectious diseases are one of the main causes of death all over the world, with antimicrobial resistance presenting a great challenge. New antibiotics need to be developed to provide therapeutic treatment options, requiring novel drug targets to be identified and pursued. DNA topoisomerases control the topology of DNA via DNA cleavage–rejoining coupled to DNA strand passage. The change in DNA topological features must be controlled in vital processes including DNA replication, transcription, and DNA repair. Type IIA topoisomerases are well established targets for antibiotics. In this review, type IA topoisomerases in bacteria are discussed as potential targets for new antibiotics. In certain bacterial pathogens, topoisomerase I is the only type IA topoisomerase present, which makes it a valuable antibiotic target. This review will summarize recent attempts that have been made to identify inhibitors of bacterial topoisomerase I as potential leads for antibiotics and use of these inhibitors as molecular probes in cellular studies. Crystal structures of inhibitor–enzyme complexes and more in-depth knowledge of their mechanisms of actions will help to establish the structure–activity relationship of potential drug leads and develop potent and selective therapeutics that can aid in combating the drug resistant bacterial infections that threaten public health.
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DOI：
10.1007/978-1-4939-7459-7_18
发表时间：
2018-01-01
期刊：
DNA TOPOISOMERASES
影响因子：
--
作者：
Annamalai, Thirunavukkarasu;Cheng, Bokun;Tse-Dinh, Yuk-Ching
通讯作者：
Tse-Dinh, Yuk-Ching
影响因子：
--
作者：
Banerjee, Bijoylaxmi;Sen, Nilkantha;Majumder, Hemanta K
通讯作者：
Majumder, Hemanta K
影响因子：
4.2
作者：
Al-Ali, Hassan;Debevec, Ginamarie;Giulianotti, Marc A.
通讯作者：
Giulianotti, Marc A.
影响因子：
3.7
作者：
Cheng B;Annamalai T;Sandhaus S;Bansod P;Tse-Dinh YC
通讯作者：
Tse-Dinh YC
影响因子：
11.8
作者：
Boucher, Helen W.;Talbot, George H.;Bartlett, John
通讯作者：
Bartlett, John