Aurora kinase as a putative target to tick control.

IF 2.1 3区医学 Q2 PARASITOLOGY

Parasitology Pub Date : 2024-11-15 DOI:10.1017/S003118202400101X

Bruno Moraes, Helga Gomes, Luiz Saramago, Valdir Braz, Luís Fernando Parizi, Gloria Braz, Itabajara da Silva Vaz, Carlos Logullo, Jorge Moraes

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Abstract

Aurora kinases (AURK) play a central role in controlling cell cycle in a wide range of organisms. They belong to the family of serine-threonine kinase proteins. Their role in the cell cycle includes, among others, the entry into mitosis, maturation of the centrosome and formation of the mitotic spindle. In mammals, 3 isoforms have been described: A, B and C, which are distinguished mainly by their function throughout the cell cycle. Two aurora kinase coding sequences have been identified in the transcriptome of the cattle tick Rhipicephalus microplus (Rm-AURKA and Rm-AURKB) containing the aurora kinase-specific domain. For both isoforms, the highest number of AURK coding transcripts is found in ovaries. Based on deduced amino acid sequences, it was possible to identify non-conserved threonine residues which are essential to AURK functions in vertebrates and which are not present in R. microplus sequences. A pan AURK inhibitor (CCT137690) caused cell viability decline in the BME26 tick embryonic cell line. In silico docking assay showed an interaction between Aurora kinase and CCT137690 with exclusive interaction sites in Rm-AURKA. The characterization of exclusive regions of the enzyme will enable new studies aimed at promoting species-specific enzymatic inhibition in ectoparasites.

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极光激酶是蜱虫控制的假定目标。

极光激酶（AURK）在多种生物的细胞周期控制中发挥着核心作用。它们属于丝氨酸-苏氨酸激酶蛋白家族。它们在细胞周期中的作用包括进入有丝分裂、中心体的成熟和有丝分裂纺锤体的形成等。在哺乳动物中，有 3 种异构体：它们主要通过在整个细胞周期中的功能来区分。在牛蜱 Rhipicephalus microplus 的转录组中发现了两个极光激酶编码序列（Rm-AURKA 和 Rm-AURKB），其中包含极光激酶特异性结构域。对于这两种异构体，卵巢中的 AURK 编码转录本数量最多。根据推导出的氨基酸序列，可以确定在脊椎动物中对 AURK 功能至关重要的非保守苏氨酸残基，而这些残基在 R. microplus 的序列中并不存在。泛 AURK 抑制剂（CCT137690）会导致 BME26 蜱胚胎细胞系的细胞活力下降。硅学对接分析表明，极光激酶与 CCT137690 在 Rm-AURKA 中的专属相互作用位点之间存在相互作用。对酶的专属区域进行表征将有助于开展新的研究，以促进对外寄生虫进行物种特异性酶抑制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Parasitology 医学-寄生虫学

CiteScore

4.80

自引率

4.20%

发文量

280

审稿时长

3-8 weeks

期刊介绍： Parasitology is an important specialist journal covering the latest advances in the subject. It publishes original research and review papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in parasite biochemistry, molecular biology and genetics, ecology and epidemiology in the context of the biological, medical and veterinary sciences. Included in the subscription price are two special issues which contain reviews of current hot topics, one of which is the proceedings of the annual Symposia of the British Society for Parasitology, while the second, covering areas of significant topical interest, is commissioned by the editors and the editorial board.