The Role of ClpP Protease in Bacterial Pathogenesis and Human Diseases,ACS Chemical Biology

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The Role of ClpP Protease in Bacterial Pathogenesis and Human Diseases
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-05-18 00:00:00 , DOI: 10.1021/acschembio.8b00124
Vaibhav Bhandari ₁ , Keith S. Wong ₁ , Jin Lin Zhou ₂ , Mark F. Mabanglo ₁ , Robert A. Batey ₂ , Walid A. Houry _{1,

2}

Affiliation

In prokaryotic cells and eukaryotic organelles, the ClpP protease plays an important role in proteostasis. The disruption of the ClpP function has been shown to influence the infectivity and virulence of a number of bacterial pathogens. More recently, ClpP has been found to be involved in various forms of carcinomas and in Perrault syndrome, which is an inherited condition characterized by hearing loss in males and females and by ovarian abnormalities in females. Hence, targeting ClpP is a potentially viable, attractive option for the treatment of different ailments. Herein, the biochemical and cellular activities of ClpP are discussed along with the mechanisms by which ClpP affects bacterial pathogenesis and various human diseases. In addition, a comprehensive overview is given of the new classes of compounds in development that target ClpP. Many of these compounds are currently primarily aimed at treating bacterial infections. Some of these compounds inhibit ClpP activity, while others activate the protease and lead to its dysregulation. The ClpP activators are remarkable examples of small molecules that inhibit protein–protein interactions but also result in a gain of function.

中文翻译：

ClpP蛋白酶在细菌发病机理和人类疾病中的作用

在原核细胞和真核细胞器中，ClpP蛋白酶在蛋白稳定中起重要作用。已经显示ClpP功能的破坏影响许多细菌病原体的感染性和毒力。最近，已经发现ClpP涉及各种形式的癌和Perrault综合征，Perrault综合征是一种遗传性疾病，其特征在于男性和女性的听力丧失以及女性的卵巢异常。因此，针对ClpP靶向治疗不同疾病可能是可行的，有吸引力的选择。在此，讨论了ClpP的生化和细胞活性以及ClpP影响细菌发病机理和各种人类疾病的机制。此外，还针对以ClpP为目标的新型化合物进行了全面概述。这些化合物中的许多目前主要用于治疗细菌感染。这些化合物中的一些抑制ClpP活性，而其他一些则激活蛋白酶并导致其失调。ClpP激活剂是抑制蛋白质与蛋白质相互作用但也导致功能获得的小分子的杰出例子。

更新日期：2018-05-18

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