Peng Zhiyuan, Ma Jian, Christov Christo Z, Karabencheva-Christova Tatyana, Lehnert Nicolai, Li Deyu
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
DNA (Basel). 2023 Jun;3(2):65-84. doi: 10.3390/dna3020005. Epub 2023 Mar 30.
Nucleic acid methylations are important genetic and epigenetic biomarkers. The formation and removal of these markers is related to either methylation or demethylation. In this review, we focus on the demethylation or oxidative modification that is mediated by the 2-oxoglutarate (2-OG)/Fe(II)-dependent AlkB/TET family enzymes. In the catalytic process, most enzymes oxidize 2-OG to succinate, in the meantime oxidizing methyl to hydroxymethyl, leaving formaldehyde and generating demethylated base. The AlkB enzyme from has nine human homologs (ALKBH1-8 and FTO) and the TET family includes three members, TET1 to 3. Among them, some enzymes have been carefully studied, but for certain enzymes, few studies have been carried out. This review focuses on the kinetic properties of those 2-OG/Fe(II)-dependent enzymes and their alkyl substrates. We also provide some discussions on the future directions of this field.
核酸甲基化是重要的遗传和表观遗传生物标志物。这些标志物的形成和去除与甲基化或去甲基化有关。在本综述中,我们重点关注由2-氧代戊二酸(2-OG)/铁(II)依赖性AlkB/TET家族酶介导的去甲基化或氧化修饰。在催化过程中,大多数酶将2-OG氧化为琥珀酸,同时将甲基氧化为羟甲基,释放甲醛并生成去甲基化碱基。来自人的AlkB酶有九个同源物(ALKBH1-8和FTO),TET家族包括三个成员,TET1至TET3。其中,一些酶已得到深入研究,但某些酶的研究较少。本综述重点关注那些2-OG/铁(II)依赖性酶及其烷基底物的动力学性质。我们还对该领域的未来方向进行了一些讨论。