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首页> 外文期刊>Biochemistry >The C-terminal domain of the adenine-DNA glycosylase MutY confers specificity for 8-oxoguanine.adenine mispairs and may have evolved from MutT, an 8-oxo-dGTPase.
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The C-terminal domain of the adenine-DNA glycosylase MutY confers specificity for 8-oxoguanine.adenine mispairs and may have evolved from MutT, an 8-oxo-dGTPase.

机译：腺嘌呤-DNA糖基化酶MutY的C端结构域赋予8-氧代鸟嘌呤。腺嘌呤错配特异性，并且可能是由8-氧代-dGTPase MutT进化而来。

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摘要

MutY is an adenine-DNA glycosylase with specificity for mismatches involving 8-oxoguanine (oG.A) or guanine (G.A). In addition to a 25 kDa catalytic domain common to all members of its DNA glycosylase superfamily, MutY has a 14 kDa C-terminal domain. Sequence analyses suggest that this C-terminal domain is distantly related to MutT, a pyrophosphohydrolase specific for 2'-deoxy-8-oxoguanosine triphosphate (doGTP). Here we present biochemical evidence that the MutT-like domain of MutY is the principal determinant of oG specificity. First, MutY dissociates approximately 1500-fold more slowly from oG-containing product DNA than from G-containing product, but a truncated protein lacking the C-terminal domain dissociates as rapidly from oG-DNA as the full-length protein dissociates from G-DNA. Second, MutY removes adenine from oG.A mismatches almost 30-fold faster than from G.A mismatches in a pre-steady-state assay, but deletion of the C-terminal domain reduces this specificity for oG.A to less than 4-fold. The kinetic data are consistent with a model in which binding of oG to the C-terminal domain of MutY accelerates the pre-steady-state glycosylase reaction by facilitating adenine base flipping. The observation that oG specificity derives almost exclusively from the C-terminal domain of MutY adds credence to the sequence analyses and suggests that specificity for oG.A mismatches was acquired by fusion of a MutT-like protein onto the core catalytic domain of an adenine-DNA glycosylase.
机译：MutY是一种腺嘌呤-DNA糖基化酶，对涉及8-氧代鸟嘌呤（oG.A）或鸟嘌呤（G.A）的错配具有特异性。除了其DNA糖基化酶超家族所有成员共有的25 kDa催化结构域外，MutY还具有14 kDa的C末端结构域。序列分析表明，此C末端结构域与MutT密切相关，MutT是特异于2'-deoxy-8-oxoguanosine triphosphate（doGTP）的焦磷酸水解酶。在这里，我们提供生化证据，证明MutY的MutT样结构域是oG特异性的主要决定因素。首先，MutY从含oG的产物DNA中解离的速度比从含G的产物中解离的速度快约1500倍，但是缺少C末端结构域的截短的蛋白质与oG-DNA的解离一样快，因为全长蛋白质从G-脱氧核糖核酸。其次，MutY从oG去除腺嘌呤。在稳态之前的分析中，A错配的速度比从G.A错配的速度快30倍，但C末端结构域的缺失将其对oG.A的特异性降低到不足4倍。动力学数据与其中oG与MutY的C末端结构域的结合通过促进腺嘌呤碱基翻转而加速稳态前糖基化酶反应的模型一致。 oG特异性几乎完全来自MutY的C末端结构域的观察结果增加了对序列分析的可信度，并表明了对oG的特异性.MutT样蛋白融合到腺嘌呤-核糖体的核心催化结构域上获得了错配。 DNA糖基化酶。

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