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单细胞病原体中的 DNA 拓扑异构酶:结构、功能与成药性。

DNA Topoisomerases in Unicellular Pathogens: Structure, Function, and Druggability.

机构信息

Laboratory of Molecular Parasitology, Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.

Laboratory of Molecular Parasitology, Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.

出版信息

Trends Biochem Sci. 2019 May;44(5):415-432. doi: 10.1016/j.tibs.2018.12.001. Epub 2019 Jan 1.

Abstract

All organisms, including unicellular pathogens, compulsorily possess DNA topoisomerases for successful nucleic acid metabolism. But particular subtypes of topoisomerases exist, in all prokaryotes and in some unicellular eukaryotes, that are absent in higher eukaryotes. Moreover, topoisomerases from pathogenic members of a niche possess some unique molecular architecture and functionalities completely distinct from their nonpathogenic colleagues. This review will highlight the unique attributes associated with the structures and functions of topoisomerases from the unicellular pathogens, with special reference to bacteria and protozoan parasites. It will also summarise the progress made in the domain pertaining to the druggability of these topoisomerases, upon which a future platform for therapeutic development can be successfully constructed.

摘要

所有生物体,包括单细胞病原体,为成功进行核酸代谢,都强制性地拥有 DNA 拓扑异构酶。但在所有原核生物和一些单细胞真核生物中,存在着特定类型的拓扑异构酶,而这些酶在高等真核生物中是不存在的。此外,来自小生境的致病成员的拓扑异构酶具有一些独特的分子结构和功能,与非致病同事完全不同。这篇综述将重点介绍与单细胞病原体的拓扑异构酶的结构和功能相关的独特属性,特别参考细菌和原生动物寄生虫。它还将总结在这些拓扑异构酶的可药性方面取得的进展,这为成功构建治疗开发的未来平台奠定了基础。

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