Kinetic Studies on the 2-Oxoglutarate/Fe(II)-Dependent Nucleic Acid Modifying Enzymes from the AlkB and TET Families.

DNA (Mary Ann Liebert, Inc.) Pub Date : 2023-06-01 Epub Date: 2023-03-30 DOI:10.3390/dna3020005
Zhiyuan Peng, Jian Ma, Christo Z Christov, Tatyana Karabencheva-Christova, Nicolai Lehnert, Deyu Li
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Abstract

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 Escherichia coli 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.

AlkB和TET家族2-氧戊二酸/Fe(II)依赖性核酸修饰酶的动力学研究
核酸甲基化是重要的遗传和表观遗传学生物标志物。这些标记物的形成和去除与甲基化或去甲基化有关。在这篇综述中,我们重点讨论了2-氧戊二酸(2-OG)/Fe(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,留下甲醛并产生脱甲基碱基。来自大肠杆菌的AlkB酶具有九种人类同源物(ALKBH1-8和FTO),TET家族包括三个成员,TET1至3。其中,一些酶已经被仔细研究,但对于某些酶,很少进行研究。本文综述了2-OG/Fe(II)依赖性酶及其烷基底物的动力学性质。我们还就这一领域的未来方向进行了一些讨论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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