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具有[4Fe-4S]簇的DNA修复糖基化酶:DNA介导的电荷传输的氧化还原辅助因子?

DNA repair glycosylases with a [4Fe-4S] cluster: a redox cofactor for DNA-mediated charge transport?

作者信息

Boal Amie K, Yavin Eylon, Barton Jacqueline K

机构信息

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

出版信息

J Inorg Biochem. 2007 Nov;101(11-12):1913-21. doi: 10.1016/j.jinorgbio.2007.05.001. Epub 2007 May 17.

Abstract

The [4Fe-4S] cluster is ubiquitous to a class of base excision repair enzymes in organisms ranging from bacteria to man and was first considered as a structural element, owing to its redox stability under physiological conditions. When studied bound to DNA, two of these repair proteins (MutY and Endonuclease III from Escherichia coli) display DNA-dependent reversible electron transfer with characteristics typical of high potential iron proteins. These results have inspired a reexamination of the role of the [4Fe-4S] cluster in this class of enzymes. Might the [4Fe-4S] cluster be used as a redox cofactor to search for damaged sites using DNA-mediated charge transport, a process well known to be highly sensitive to lesions and mismatched bases? Described here are experiments demonstrating the utility of DNA-mediated charge transport in characterizing these DNA-binding metalloproteins, as well as efforts to elucidate this new function for DNA as an electronic signaling medium among the proteins.

摘要

[4Fe-4S]簇在从细菌到人类的生物体中一类碱基切除修复酶中普遍存在,由于其在生理条件下的氧化还原稳定性,最初被认为是一种结构元件。当研究其与DNA结合时,其中两种修复蛋白(来自大肠杆菌的MutY和核酸内切酶III)表现出依赖于DNA的可逆电子转移,具有高电位铁蛋白的典型特征。这些结果促使人们重新审视[4Fe-4S]簇在这类酶中的作用。[4Fe-4S]簇是否可以用作氧化还原辅因子,通过DNA介导的电荷传输来寻找受损位点,而这一过程众所周知对损伤和错配碱基高度敏感?本文描述了一些实验,这些实验证明了DNA介导的电荷传输在表征这些DNA结合金属蛋白方面的效用,以及阐明DNA作为蛋白质间电子信号介质这一新功能的努力。

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