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细菌金属氨基肽酶作为人类传染病的靶点。

Bacterial Metalo-Aminopeptidases as Targets in Human Infectious Diseases.

机构信息

Department of Biochemistry, Faculty of Biology, University of Havana, Calle 25 #455 Entre I y J, 10400, Vedado, La Habana, Cuba.

Center for Protein Studies, University of Havana, Calle 25 #455 Entre I y J, 10400, Vedado, La Habana, Cuba.

出版信息

Curr Drug Targets. 2022;23(12):1155-1190. doi: 10.2174/1389450123666220316085859.

Abstract

BACKGROUND

Human infectious diseases caused by bacteria are a worldwide health problem due to the increased resistance of these microorganisms to conventional antibiotics. For this reason, the identification of novel molecular targets and the discovery of new antibacterial compounds are urgently required. Metalo-aminopeptidases are promising targets in bacterial infections. They participate in crucial processes for bacterial growth and pathogenesis, such as protein and peptide degradation to supply amino acids, protein processing, access to host tissues, cysteine supply for redox control, transcriptional regulation, site-specific DNA recombination, and hydrogen sulfide production. Although several of these enzymes are not essential, they are required for virulence and maximal growth in conditions of nutrient limitation and high temperatures.

OBJECTIVE

In this review, we describe the structural, functional, and kinetic properties of some examples of bacterial metalo-aminopeptidases, in the context of their use as antibacterial targets. In addition, we present some inhibitors reported for these enzymes.

CONCLUSION

It is necessary to conduct a meticulous work to validate these peptidases as good/bad targets and to identify inhibitors with potential therapeutic use.

摘要

背景

由于这些微生物对传统抗生素的耐药性增加,由细菌引起的人类传染病成为了一个全球性的健康问题。因此,迫切需要鉴定新的分子靶点和发现新的抗菌化合物。金属氨肽酶是细菌感染的有前途的靶点。它们参与了细菌生长和发病机制的关键过程,例如蛋白质和肽的降解以提供氨基酸、蛋白质加工、进入宿主组织、半胱氨酸供应用于氧化还原控制、转录调节、特定于位点的 DNA 重组和硫化氢产生。尽管其中一些酶不是必需的,但它们对于在营养限制和高温条件下的毒力和最大生长是必需的。

目的

在本文综述中,我们描述了一些细菌金属氨肽酶的结构、功能和动力学特性,以及它们作为抗菌靶点的应用。此外,我们还介绍了一些针对这些酶的抑制剂。

结论

有必要进行细致的工作来验证这些肽酶作为好/坏靶标,并识别具有潜在治疗用途的抑制剂。

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