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首页> 外文期刊>Parasitology >Bioinformatic analysis of glycogen synthase kinase 3: Human versus parasite kinases
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Bioinformatic analysis of glycogen synthase kinase 3: Human versus parasite kinases

机译：糖原合酶激酶3的生物信息学分析：人与寄生虫激酶

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Objective. Glycogen synthase kinase 3 (GSK-3) is a promising target for the treatment of various human diseases such as type 2 diabetes, Alzheimer's disease and inflammation. Successful inhibition of the homologues of this kinase in Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani makes the kinase an attractive target for the treatment of malaria, trypanosomiasis and leishmaniasis, respectively. The aim of this work was to compare the binding sites of the GSK-3 kinases of different parasites and to analyse them as possible targets for therapeutic compounds. Methods. Both a sequence alignment and homology models of the structure of 21 different GSK-3 homologues belonging to mammals, insects, pathogenic fungi, nematodes, trematodes and protozoa have been analysed, 17 of them being studied for the first time. Results. The structure of the kinases and, in particular, their binding sites, were found to be rather conserved, possessing small insertions or deletions and conserved amino acid substitutions. Nevertheless, the kinases of most species of parasite did have some amino acid differences from the human kinase, which could be exploited for the design of selective drugs. Conclusion. Comparison of the human and parasite GSK-3 ATP binding site models has shown that the development of selective drugs affecting parasite GSK-3 is possible. Known inhibitors of human GSK-3 can also be used as starting scaffolds for the search for drugs acting against parasitic diseases.
机译：目的。糖原合酶激酶3（GSK-3）是治疗各种人类疾病（如2型糖尿病，阿尔茨海默氏病和炎症）的有希望的靶标。成功抑制恶性疟原虫，布鲁氏锥虫和杜氏利什曼原虫中该激酶的同源物，使得该激酶分别成为治疗疟疾，锥虫病和利什曼病的有吸引力的靶标。这项工作的目的是比较不同寄生虫的GSK-3激酶的结合位点，并将其分析为治疗性化合物的可能靶标。方法。已对21种不同的GSK-3同源物的结构的序列比对和同源性模型进行了分析，它们分别属于哺乳动物，昆虫，病原性真菌，线虫，吸虫和原生动物，其中17种是首次研究。结果。发现激酶的结构，特别是它们的结合位点是相当保守的，具有小的插入或缺失和保守的氨基酸取代。然而，大多数寄生虫的激酶与人激酶的确有一些氨基酸差异，可用于设计选择性药物。结论。人和寄生虫GSK-3 ATP结合位点模型的比较表明，可能开发出影响寄生虫GSK-3的选择性药物。已知的人类GSK-3抑制剂也可以用作起始支架，以寻找对抗寄生虫病的药物。

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