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极光激酶作为蜱虫防治的潜在靶点。

Aurora kinase as a putative target to tick control.

作者信息

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

机构信息

Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, RJ, Brazil.

Laboratório Integrado de Bioquímica Hatisaburo Masuda, NUPEM-Universidade Federal do Rio de Janeiro campus Macaé, Brazil.

出版信息

Parasitology. 2024 Aug;151(9):983-991. doi: 10.1017/S003118202400101X. Epub 2024 Nov 15.

DOI:10.1017/S003118202400101X
PMID:39542861
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11770520/
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 (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 sequences. A pan AURK inhibitor (CCT137690) caused cell viability decline in the BME26 tick embryonic cell line. 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.

摘要

极光激酶（AURK）在多种生物体的细胞周期控制中发挥核心作用。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、中心体成熟和有丝分裂纺锤体形成等。在哺乳动物中，已描述了3种亚型：A、B和C，它们主要通过在整个细胞周期中的功能来区分。在牛蜱的转录组中已鉴定出两个极光激酶编码序列（Rm - AURKA和Rm - AURKB），其含有极光激酶特异性结构域。对于这两种亚型，在卵巢中发现的AURK编码转录本数量最多。基于推导的氨基酸序列，有可能鉴定出对脊椎动物中AURK功能至关重要且在序列中不存在的非保守苏氨酸残基。一种泛极光激酶抑制剂（CCT137690）导致BME26蜱胚胎细胞系的细胞活力下降。对接试验表明极光激酶与CCT137690之间存在相互作用，且在Rm - AURKA中有独特的相互作用位点。对该酶独特区域的表征将有助于开展旨在促进对外寄生虫进行物种特异性酶抑制的新研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/c1107a305bc9/S003118202400101X_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/1b3cac940f72/S003118202400101X_figAb.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/dca76ef147d0/S003118202400101X_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/af588a81cdb2/S003118202400101X_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/a743b00afee6/S003118202400101X_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/031256737fb0/S003118202400101X_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/43d663fdddd4/S003118202400101X_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/2804667c643c/S003118202400101X_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/22324ad17b9f/S003118202400101X_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/c1107a305bc9/S003118202400101X_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/1b3cac940f72/S003118202400101X_figAb.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/dca76ef147d0/S003118202400101X_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/af588a81cdb2/S003118202400101X_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/a743b00afee6/S003118202400101X_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/031256737fb0/S003118202400101X_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/43d663fdddd4/S003118202400101X_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/2804667c643c/S003118202400101X_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/22324ad17b9f/S003118202400101X_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edb5/11770520/c1107a305bc9/S003118202400101X_fig8.jpg

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