The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?
The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?
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DOI：
10.3390/cells10020299
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发表时间：
2021-02-01
期刊：
影响因子：
6
通讯作者：
d'Avila-Levy CM
中科院分区：
文献类型：
--
作者：
Ennes-Vidal V;Branquinha MH;Dos Santos ALS;d'Avila-Levy CM
钙蛋白酶是最初在哺乳动物中描述的钙依赖性半胱氨酸肽酶，此后，在几乎所有已知的活生物体中鉴定了它们的同源物。这些肽酶的活性失调与几种病理学有关，因此，人们做出了巨大的努力来鉴定选择性抑制剂。锥虫是导致人类生命受到威胁的重要病原体，其基因组中含有大量不同的钙蛋白酶序列。考虑到目前治疗锥虫病的疗法仅限于少数几种药物，这些药物具有不可接受的毒性，坚韧的给药途径（如胃肠外）和增加的治疗失败，钙蛋白酶抑制剂的重新利用方法可能是成功化疗的捷径。然而，有一个普遍缺乏知识的钙蛋白酶在这些寄生虫的功能，目前，这些蛋白质的蛋白水解活性仍然是一个悬而未决的问题。在这里，我们强调了目前的研究和锥虫钙蛋白酶的观点，概述钙蛋白酶在这些生物体的描述，并探讨潜在的针对钙蛋白酶系统作为一种治疗策略。这篇综述收集了目前的知识，这个迷人的家族的肽酶以及洞察的难题：我们无法测量钙蛋白酶活性锥虫，或者是这些蛋白质的功能缺乏蛋白水解活性在这些寄生虫？
Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?
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影响因子：
64.8
作者：
Hanna, Rachel A.;Campbell, Robert L.;Davies, Peter L.
通讯作者：
Davies, Peter L.
影响因子：
4.2
作者：
de Oliveira SS;Garcia-Gomes Ados S;d'Avila-Levy CM;dos Santos AL;Branquinha MH
通讯作者：
Branquinha MH
DOI：
10.1016/j.ijantimicag.2006.03.021
发表时间：
2006-08-01
影响因子：
10.8
作者：
d'Avila-Levy, Claudia M.;Marinho, Fernanda A.;Branquinha, Marta H.
通讯作者：
Branquinha, Marta H.
影响因子：
1.5
作者：
Hertz-Fowler, C;Ersfeld, K;Gull, K
通讯作者：
Gull, K
影响因子：
2.4
作者：
Ennes-Vidal V;Menna-Barreto RF;Branquinha MH;Dos Santos AL;D'Avila-Levy CM
通讯作者：
D'Avila-Levy CM