Microbial proteasomes as drug targets.
Microbial proteasomes as drug targets.
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微生物蛋白酶体作为药物靶点。
DOI：
10.1371/journal.ppat.1010058
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发表时间：
2021-12
期刊：
影响因子：
6.7
通讯作者：
Lin G
中科院分区：
文献类型：
--
作者：
Zhang H;Lin G
蛋白酶体是一种具有ATP依赖性的N端亲核水解酶，在细胞内蛋白质周转中起重要作用。他们存在于所有三个王国。蛋白酶体的药理学抑制对细胞活力有害。蛋白酶体抑制剂地毯彻底改变了多发性骨髓瘤的治疗。病原微生物如结核分枝杆菌（Mtb）、恶性疟原虫（Pf）和其他寄生虫和蠕虫中的蛋白酶体已被验证为治疗靶标。从结核分枝杆菌蛋白酶体开始，近年来对微生物蛋白酶体选择性抑制剂的研究取得了很大进展。在这篇综述中，我们描述的策略和药效团已被用于开发蛋白酶体抑制剂的效力和选择性，备用人类蛋白酶体和突出发展的临床蛋白酶体抑制剂候选治疗利什曼病和恰加斯病。最后，我们讨论了微生物蛋白酶体抑制剂的未来挑战和治疗潜力。
Proteasomes are compartmentalized, ATP-dependent, N-terminal nucleophile hydrolases that play essentials roles in intracellular protein turnover. They are present in all 3 kingdoms. Pharmacological inhibition of proteasomes is detrimental to cell viability. Proteasome inhibitor rugs revolutionize the treatment of multiple myeloma. Proteasomes in pathogenic microbes such as Mycobacterium tuberculosis (Mtb), Plasmodium falciparum (Pf), and other parasites and worms have been validated as therapeutic targets. Starting with Mtb proteasome, efforts in developing inhibitors selective for microbial proteasomes have made great progress lately. In this review, we describe the strategies and pharmacophores that have been used in developing proteasome inhibitors with potency and selectivity that spare human proteasomes and highlight the development of clinical proteasome inhibitor candidates for treatment of leishmaniasis and Chagas disease. Finally, we discuss the future challenges and therapeutical potentials of the microbial proteasome inhibitors.
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影响因子：
3.6
作者：
Cerda-Maira FA;Pearce MJ;Fuortes M;Bishai WR;Hubbard SR;Darwin KH
通讯作者：
Darwin KH
影响因子：
2.7
作者：
Akama T;Zhang YK;Freund YR;Berry P;Lee J;Easom EE;Jacobs RT;Plattner JJ;Witty MJ;Peter R;Rowan TG;Gillingwater K;Brun R;Nare B;Mercer L;Xu M;Wang J;Liang H
通讯作者：
Liang H
影响因子：
6.7
作者：
Gandotra S;Lebron MB;Ehrt S
通讯作者：
Ehrt S
影响因子：
3.6
作者：
Hu, GQ;Lin, G;Li, HL
通讯作者：
Li, HL
影响因子：
56.9
作者：
Darwin, KH;Ehrt, S;Nathan, CF
通讯作者：
Nathan, CF