Human Sirtuin 2 inhibitors, Their Mechanisms and Binding Modes
André Berndt Penteado, Haifa Hassanie, Renan Augusto Gomes, Flávio da Silva Emery, Gustavo Henrique Goulart Trossini
Abstract
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.