Schizosaccharomyces pombe Ofd2 Is a Nuclear 2-Oxoglutarate and Iron Dependent Dioxygenase Interacting with Histones
Schizosaccharomyces pombe Ofd2 Is a Nuclear 2-Oxoglutarate and Iron Dependent Dioxygenase Interacting with Histones
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DOI：
10.1371/journal.pone.0025188
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发表时间：
2011-09-16
期刊：
影响因子：
3.7
通讯作者：
Alseth, Ingrun
中科院分区：
文献类型：
--
作者：
Korvald, Hanne;Moe, Anne Margrethe Molstad;Alseth, Ingrun
2-酮戊二酸（2OG）依赖性双加氧酶是普遍存在的含铁酶，其将底物氧化与2OG转化为琥珀酸和二氧化碳偶联。它们参与广泛的生物学过程，包括胶原蛋白生物合成、脂肪酸代谢、缺氧传感以及核酸和组蛋白的去甲基化。虽然在阐明其功能方面取得了实质性进展，但许多2OG双加氧酶的作用仍然是谜。在这里，我们研究了2OG和铁（Fe（II））依赖性双加氧酶Ofd2裂殖酵母，AlkB亚家族的双加氧酶的成员。我们表明，脱羧的2OG重组Ofd2是依赖于铁（II）和组氨酸残基预测参与Fe（II）的协调。Ofd2的脱羧酶活性受到组蛋白的刺激，并且H2A具有最强的作用。然而，Ofd2与所有四种核心组蛋白相互作用，仅与H4非常弱。我们的研究结果定义了一个新的亚类的AlkB蛋白与组蛋白相互作用，这也可能包括一些人类AlkB同系物与未知功能。
2-oxoglutarate (2OG) dependent dioxygenases are ubiquitous iron containing enzymes that couple substrate oxidation to the conversion of 2OG to succinate and carbon dioxide. They participate in a wide range of biological processes including collagen biosynthesis, fatty acid metabolism, hypoxic sensing and demethylation of nucleic acids and histones. Although substantial progress has been made in elucidating their function, the role of many 2OG dioxygenases remains enigmatic. Here we have studied the 2OG and iron (Fe(II)) dependent dioxygenase Ofd2 in Schizosaccharomyces pombe, a member of the AlkB subfamily of dioxygenases. We show that decarboxylation of 2OG by recombinant Ofd2 is dependent on Fe(II) and a histidine residue predicted to be involved in Fe(II) coordination. The decarboxylase activity of Ofd2 is stimulated by histones, and H2A has the strongest effect. Ofd2 interacts with all four core histones, however, only very weakly with H4. Our results define a new subclass of AlkB proteins interacting with histones, which also might comprise some of the human AlkB homologs with unknown function.