Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of NAD(+)-dependent protein N(ε)-acetyl-lysine (AcK) deacetylases. Sirtuins are also evolutionarily conserved proteins that are present in all kingdoms of life ranging from bacteria to humans. Interestingly, it was recently found that the sirtuins found in various human parasites (especially the Plasmodium, Trypanosoma, and Leishmania species) were pro-survival for the parasites under various conditions. Therefore, these parasitic sirtuins have emerged as novel anti-parasitic therapeutic targets. This article reviews the currently available structural, biochemical, pharmacological, and medicinal chemistry studies on these enzymes, and discusses the perspectives of selectively targeting the parasitic sirtuins as a novel therapeutic strategy for the human parasitic diseases.

译文

:沉默信息调节剂2(Sir2)酶或sirtuins是NAD()依赖性蛋白N(ε)-乙酰赖氨酸(AcK)脱乙酰基酶的一个家族。 Sirtuins还是进化上保守的蛋白质,存在于从细菌到人类的所有生命王国中。有趣的是,最近发现在各种人类寄生虫(尤其是疟原虫,锥虫和利什曼原虫)中发现的沉默调节蛋白在各种条件下均可存活。因此,这些寄生沉默调节蛋白已经成为新型的抗寄生虫治疗靶标。本文回顾了有关这些酶的当前可用的结构,生化,药理和药物化学研究,并讨论了选择性靶向寄生虫沉默调节蛋白作为人类寄生虫疾病的新型治疗策略的观点。

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