Department of Chemistry, KU Leuven, Celestijnenlaan 200G, B-3001, Heverlee, Belgium.
Department of Chemistry, KU Leuven, Celestijnenlaan 200G, B-3001, Heverlee, Belgium.
DNA Repair (Amst). 2020 Dec;96:102995. doi: 10.1016/j.dnarep.2020.102995. Epub 2020 Oct 8.
Iron-dependent dioxygenases of the AlkB protein family found in most organisms throughout the tree of life play a major role in oxidative dealkylation processes. Many of these enzymes have attracted the attention of researchers across different fields and have been subjected to thorough biochemical characterization because of their link to human health and disease. For example, several mammalian AlkB homologues are involved in the direct reversal of alkylation damage in DNA, while others have been shown to play a regulatory role in epigenetic or epitranscriptomic nucleic acid methylation or in post-translational modifications such as acetylation of actin filaments. These studies show that that divergence in amino acid sequence and structure leads to different characteristics and substrate specificities. In this review, we aim to summarize current insights in the structural features involved in the substrate selection of AlkB homologues, with focus on nucleic acid interactions.
生命之树中大多数生物体内都存在依赖铁的 AlkB 蛋白家族双氧酶，它们在氧化脱烷基化过程中发挥着主要作用。由于这些酶与人类健康和疾病有关，许多此类酶引起了不同领域研究人员的关注，并对其进行了深入的生化特性分析。例如，几种哺乳动物 AlkB 同源物参与 DNA 中烷基化损伤的直接逆转，而其他 AlkB 同源物则被证明在表观遗传或转录后核酸甲基化或肌动蛋白丝乙酰化等翻译后修饰中发挥调节作用。这些研究表明，氨基酸序列和结构的差异导致了不同的特性和底物特异性。在这篇综述中，我们旨在总结 AlkB 同源物在底物选择中涉及的结构特征的最新认识，重点关注核酸相互作用。
