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首页> 外文期刊>Journal of Molecular Biology >New insights on the role of the gamma-herpesvirus uracil-DNA glycosylase leucine loop revealed by the structure of the Epstein-Barr virus enzyme in complex with an inhibitor protein
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New insights on the role of the gamma-herpesvirus uracil-DNA glycosylase leucine loop revealed by the structure of the Epstein-Barr virus enzyme in complex with an inhibitor protein

机译：通过与抑制剂蛋白复合的爱泼斯坦-巴尔病毒酶结构揭示γ-疱疹病毒尿嘧啶-DNA糖基化酶亮氨酸环作用的新见解

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Epstein-Barr virus (EBV) is a human gamma-herpesvirus. Within its 86 open reading frame containing genome, two enzymes avoiding uracil incorporation into DNA can be found: uracil triphosphate hydrolase and uracil-DNA glycosylase (UNG). The latter one excises uracil bases that are due to cytosine deamination or uracil misincorporation. from double-stranded DNA substrates. The EBV enzyme belongs to family 1 UNGs. We solved the three-dimensional structure of EBV UNG, in complex with the uracil-DNA glycosylase inhibitor protein (Ugi) from bacteriophage PBS-2 at a resolution of 2.3 angstrom by X-ray crystallography. The structure of EBV UNG encoded by the BKRF3 reading frame shows the excellent global structural conservation within the solved examples of family I enzymes. Four out of the five catalytic motifs are completely conserved, whereas the fifth one, the leucine loop, carries a seven residue insertion. Despite this insertion, catalytic constants of EBV UNG are similar to those of other UNGs. Modelling of the EBV UNG-DNA complex shows that the longer leucine loop still contacts DNA and is likely to fulfil its role of DNA binding and deformation differently than the enzymes with previously solved structures. We could show that despite the evolutionary distance of EBV UNG from the natural host protein, bacteriophage Ugi binds with an inhibitory constant of 8 nM to UNG. This is due to an excellent specificity of Ugi for conserved elements of UNG, four of them corresponding to catalytic motifs and a fifth one corresponding to an important beta-turn structuring the catalytic site. (c) 2006 Elsevier Ltd. All rights reserved.
机译：爱泼斯坦-巴尔病毒（EBV）是一种人类伽马疱疹病毒。在包含基因组的86个开放阅读框内，可以找到两种避免尿嘧啶掺入DNA的酶：尿嘧啶三磷酸水解酶和尿嘧啶DNA糖基化酶（UNG）。后者切除由于胞嘧啶脱氨基或尿嘧啶错误掺入而引起的尿嘧啶碱基。来自双链DNA底物。 EBV酶属于1类UNGs。我们通过X射线晶体学分析了与噬菌体PBS-2中尿嘧啶DNA糖基化酶抑制剂蛋白（Ugi）形成复合体的EBV UNG的三维结构，其分辨率为2.3埃。由BKRF3阅读框编码的EBV UNG的结构在I类酶的已解析实例中显示了出色的整体结构保守性。五个催化基序中的四个完全保守，而第五个亮氨酸环带有七个残基插入。尽管有这种插入，但EBV UNG的催化常数与其他UNG的相似。 EBV UNG-DNA复合物的模型表明，较长的亮氨酸环仍与DNA接触，并且与以前具有结构解析的酶相比，它可能以不同的方式履行其DNA结合和变形的作用。我们可以证明，尽管EBV UNG与天然宿主蛋白的进化距离较远，但噬菌体Ugi与UNG的结合抑制常数为8 nM。这是由于Ugi对UNG的保守元素具有极好的特异性，其中四个对应于催化基序，第五个对应于构成催化位点的重要β-转角。 （c）2006 Elsevier Ltd.保留所有权利。

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