Penteado André Berndt, Hassanie Haifa, Gomes Renan Augusto, Silva Emery Flávio da, Goulart Trossini Gustavo Henrique
School of Pharmaceutical Sciences, University of São Paulo, Av. Lineu Prestes, 580, Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Café, s/n, Ribeirão Preto, SP, 14040-903, Brazil.
Future Med Chem. 2023 Feb;15(3):291-311. doi: 10.4155/fmc-2022-0253. Epub 2023 Mar 9.
The silent information regulator (sirtuin) is a family of enzymes involved in epigenetic processes with lysine deacetylase activity, having as substrates histones and other proteins. They participate in a wide range of cellular and pathologic processes, such as gene expression, cell division and motility, oxidative-induced stress management, metabolic control and carcinogenesis, among others, thus presenting as interesting therapeutic targets. In this article, the authors describe the inhibitory mechanisms and binding modes of the human sirtuin 2 (hSIRT2) inhibitors, which had their complexes with the enzyme structurally characterized. The results help pave the way for the rational designing of new hSIRT2 inhibitors and the development of novel therapeutic agents targeting this epigenetic enzyme.
沉默信息调节因子（sirtuin）是一类参与表观遗传过程的酶家族，具有赖氨酸脱乙酰酶活性，其底物包括组蛋白和其他蛋白质。它们参与广泛的细胞和病理过程，如基因表达、细胞分裂与运动、氧化应激管理、代谢控制和致癌作用等，因此成为有趣的治疗靶点。在本文中，作者描述了人类沉默信息调节因子2（hSIRT2）抑制剂的抑制机制和结合模式，这些抑制剂与该酶的复合物已通过结构表征。这些结果有助于为合理设计新型hSIRT2抑制剂以及开发针对这种表观遗传酶的新型治疗药物铺平道路。
