Hildmann Christian, Wegener Dennis, Riester Daniel, Hempel René, Schober Andreas, Merana Joachim, Giurato Laura, Guccione Salvatore, Nielsen Tine Kragh, Ficner Ralf, Schwienhorst Andreas
Department of Molecular Genetics and Preparative Molecular Biology Institute for Microbiology und Genetics, Goettingen, Germany.
J Biotechnol. 2006 Jun 25;124(1):258-70. doi: 10.1016/j.jbiotec.2006.01.030. Epub 2006 Mar 29.
Histone deacetylases (HDACs) are key enzymes in the transcriptional regulation of gene expression in eukaryotic cells. In recent years HDACs have attracted considerable attention as promising new targets in anticancer therapy. Currently, different histone deacetylase subtypes are divided into four groups denoted as classes 1-4. Here, we compare in more detail representatives of class 1 HDACs and FB188 HDAH as a close bacterial homologue of class 2 HDAC6, in regard of substrate and inhibitor specificity. Structure comparison is used to identify candidate regions responsible for observed specificity differences. Knowledge of these structural elements expedite studies on the biochemical role of different HDAC subtypes as well as the development of highly selective HDAC inhibitors as antitumor agents.
组蛋白去乙酰化酶（HDACs）是真核细胞中基因表达转录调控的关键酶。近年来，HDACs作为抗癌治疗中有前景的新靶点受到了广泛关注。目前，不同的组蛋白去乙酰化酶亚型分为1-4类。在此，我们更详细地比较了1类HDACs的代表与FB188 HDAH（作为2类HDAC6的紧密细菌同源物）在底物和抑制剂特异性方面的情况。通过结构比较来确定导致观察到的特异性差异的候选区域。了解这些结构元件有助于加快对不同HDAC亚型生化作用的研究，以及开发作为抗肿瘤药物的高选择性HDAC抑制剂。
