State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia University, Hohhot 010021, China.
Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China; University of Chinese Academy of Sciences, Beijing, China.
Int J Biol Macromol. 2024 Oct;278(Pt 4):134798. doi: 10.1016/j.ijbiomac.2024.134798. Epub 2024 Aug 15.
Histone lysine demethylase (KDM), AlkB homolog (ALKBH), and Ten-Eleven Translocation (TET) proteins are members of the 2-Oxoglutarate (2OG) and ferrous iron-dependent oxygenases, each of which harbors a catalytic domain centered on a double-stranded β-helix whose topology restricts the regions directly involved in substrate binding. However, they have different catalytic functions, and the deeply structural biological reasons are not yet clear. In this review, the catalytic domain features of the three protein families are summarized from both sequence and structural perspectives. The construction of the phylogenetic tree and comparison of the structure show ten relatively conserved β-sheets and three key regions with substantial structural differences. We summarize the relationship between three key regions of remarkable differences and the substrate compatibility of the three protein families. This review facilitates research into substrate-selective inhibition and bioengineering by providing new insights into the catalytic domains of KDM, ALKBH, and TET proteins.
组蛋白赖氨酸去甲基酶（KDM）、 AlkB 同系物（ALKBH）和 Ten-Eleven 易位（TET）蛋白是 2-氧戊二酸（2OG）和亚铁依赖性加氧酶的成员，每个蛋白都包含一个以双链β-螺旋为中心的催化结构域，其拓扑结构限制了直接参与底物结合的区域。然而，它们具有不同的催化功能，其深层次的结构生物学原因尚不清楚。在这篇综述中，从序列和结构的角度总结了这三种蛋白家族的催化结构域特征。系统发育树的构建和结构的比较表明，它们有十个相对保守的β-折叠和三个关键区域，这些区域具有显著的结构差异。我们总结了三个关键区域的显著差异与三种蛋白家族的底物兼容性之间的关系。本综述通过为 KDM、ALKBH 和 TET 蛋白的催化结构域提供新的见解，促进了对底物选择性抑制和生物工程的研究。
