Dimeric dUTPases, HisE, and MazG belong to a new superfamily of all-α NTP pyrophosphohydrolases with potential "house-cleaning" functions
Dimeric dUTPases, HisE, and MazG belong to a new superfamily of all-α NTP pyrophosphohydrolases with potential "house-cleaning" functions
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DOI：
10.1016/j.jmb.2005.01.030
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发表时间：
2005-03-25
影响因子：
5.6
通讯作者：
Galperin, MY
中科院分区：
文献类型：
--
作者：
Moroz, OV;Murzin, AG;Galperin, MY
新的二聚体dUTR家族的结构指导分析揭示了其与噬菌体T4 dCTR、磷酸核糖基-ATP焦磷酸酶HisE、NTP焦磷酸酶MazG和几个未表征的蛋白质家族的序列关系，包括在胚胎和癌细胞中过表达的人蛋白XTP 3 TPA（RS 21-C6）。与最近确定的MazG样蛋白质的结构比较硫磺硫化叶菌支持这些酶在一个超家族的所有α NTP焦磷酸酶的统一，这表明二聚体dUTPases从一个四聚体MazG样祖先的基因复制。Sulfolobus MazG的结构分析指出，ATP氧化损伤的产物2-羟基腺苷（异鸟苷）三磷酸是最可能的底物。我们预测，这个超家族的未表征的成员通过水解异常的NTPs来执行“房屋清洁”功能，并且在功能上类似于结构上不相关的水解酶的Nutrium超家族。我们概述了所有α-NTP焦磷酸酶超家族成员可能的三级和四级结构。(c)2005爱思唯尔有限公司保留所有权利。
Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE, NTP pyrophosphatase MazG, and several uncharacterized protein families, including the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and cancer cells. Comparison with the recently determined structure of a MazG-like protein from Sulfolobus solfataricus supported the unification of these enzymes in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication. Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most likely substrate. We predict that uncharacterized members of this superfamily perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are functionally analogous to the structurally unrelated hydrolases of the Nudix superfamily. We outline probable tertiary and quaternary structures of the all-alpha NTP pyrophosphatase superfamily members. (c) 2005 Elsevier Ltd. All rights reserved.