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首页> 外文期刊>Journal of Molecular Biology >A new protein architecture for processing alkylation damaged DNA: the crystal structure of DNA glycosylase AlkD.
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A new protein architecture for processing alkylation damaged DNA: the crystal structure of DNA glycosylase AlkD.

机译：处理烷基化受损DNA的新蛋白质结构：DNA糖基化酶AlkD的晶体结构。

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摘要

DNA glycosylases safeguard the genome by locating and excising chemically modified bases from DNA. AlkD is a recently discovered bacterial DNA glycosylase that removes positively charged methylpurines from DNA, and was predicted to adopt a protein fold distinct from from those of other DNA repair proteins. The crystal structure of Bacillus cereus AlkD presented here shows that the protein is composed exclusively of helical HEAT-like repeats, which form a solenoid perfectly shaped to accommodate a DNA duplex on the concave surface. Structural analysis of the variant HEAT repeats in AlkD provides a rationale for how this protein scaffolding motif has been modified to bind DNA. We report 7mG excision and DNA binding activities of AlkD mutants, along with a comparison of alkylpurine DNA glycosylase structures. Together, these data provide important insight into the requirements for alkylation repair within DNA and suggest that AlkD utilizes a novel strategy to manipulate DNA in its search for alkylpurine bases.
机译：DNA糖基化酶通过从DNA中定位和切除化学修饰的碱基来保护基因组。 AlkD是最近发现的细菌DNA糖基化酶，可从DNA上去除带正电荷的甲基嘌呤，并被预测会采用不同于其他DNA修复蛋白的蛋白质折叠。此处显示的蜡状芽孢杆菌AlkD的晶体结构表明，该蛋白质仅由螺旋状的HEAT样重复序列组成，形成了一个螺线管，形状完美，可在凹面容纳DNA双链体。对AlkD中HEAT重复序列的变异进行结构分析，为该蛋白支架基序如何被修饰以结合DNA提供了理论依据。我们报告AlkD突变体的7mG切除和DNA结合活性，以及​​烷基嘌呤DNA糖基化酶结构的比较。总之，这些数据提供了对DNA内烷基化修复要求的重要见解，并表明AlkD在寻找烷基嘌呤碱基时利用了一种新颖的策略来操纵DNA。

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