Functional elucidation of YbiB - the defining member of the novel TrpD2 family of prokaryotic nucleoside triphosphatases
YbiB 的功能阐明 - 原核核苷三磷酸酶新型 TrpD2 家族的定义成员
基本信息
- 批准号:351626320
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2017
- 资助国家:德国
- 起止时间:2016-12-31 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The aim of this project is the functional elucidation of the enzyme YbiB from Escherichia coli as a defining member of the hitherto uncharacterized TrpD2 protein family. The TrpD2 proteins show high structural similarity both to anthranilate phosphoribosyltransferase (TrpD), an enzyme from tryptophan biosynthesis, and to class II nucleoside phosphorylases (NP-II), which play an important role in the nucleotide salvage pathway. However, we could neither detect TrpD activity nor NP-II activity for YbiB. The crystal structure of YbiB shows two prominent positively charged grooves on the surface of the dimeric protein, which are responsible for the high-affinity binding of nucleic acids. Interestingly, the ybiB gene is located in a LexA-regulated operon. The LexA repressor controls the bacterial SOS response to DNA damage. Based on these results we hypothesized that YbiB and thereby the TrpD2 proteins represent a hitherto unknown component of the SOS system.In accordance with this hypothesis, we could recently show that YbiB has an 8-oxo-dGTP-specific triphosphatase activity. The relevance of this activity is the removal of oxidatively damaged dGTP from the nucleotide pool. In spite of the presence of the iso-functional Nudix hydrolase MutT in many organisms, the existence of a second enzyme like YbiB is biologically meaningful: MutT also hydrolyzes the four standard nucleotides to a certain extent, whereas YbiB does not show this side reaction. Therefore, the expression of YbiB could be increased in the SOS case to a significantly higher level without negative effects for the nucleotide pool.Our aim is to characterize in detail the function of YbiB and other TrpD2 representatives in the context of DNA repair and nucleotide pool sanitation. First, we will investigate whether 8-oxo-dGTP is the main substrate of these enzymes, or whether other damaged nucleotides are converted with similar or even higher efficiency. Furthermore, we will test whether the binding of nucleic acids or proteins enhances the relatively low activity of YbiB. Additionally, we plan to co-crystallize YbiB with substrate analogues and nucleic acids. The resulting structures will contribute to our understanding of the mode of function of the TrpD2 proteins. Finally, we will examine the structure-function relationships within the phosphoribosyltransferase class III superfamily with its members TrpD2, TrpD and NP-II. Thus, the planned experiments will not only elucidate the function of a hitherto unknown member of the SOS response, but also shed light on the evolution of an interesting protein superfamily.
该项目的目的是从大肠杆菌中的酶YbiB的功能阐明作为迄今未表征的TrpD 2蛋白家族的定义成员。TrpD 2蛋白质显示出与邻氨基苯甲酸磷酸核糖基转移酶(TrpD)(色氨酸生物合成的酶)和II类核苷磷酸化酶(NP-II)(其在核苷酸补救途径中起重要作用)的高度结构相似性。然而,我们既不能检测到YbiB的TrpD活性,也不能检测到NP-II活性。YbiB的晶体结构在二聚体蛋白的表面上显示出两个突出的带正电荷的凹槽,这是核酸高亲和力结合的原因。有趣的是,ybiB基因位于LexA调控的操纵子中。莱克萨阻遏物控制细菌对DNA损伤的SOS反应。基于这些结果,我们假设YbiB和TrpD 2蛋白代表SOS系统的一种迄今未知的组分。根据这一假设,我们最近可以证明YbiB具有8-oxo-dGTP特异性三磷酸酶活性。该活性的相关性是从核苷酸库中去除氧化损伤的dGTP。尽管在许多生物体中存在同功能的NutT水解酶MutT,但第二种酶如YbiB的存在具有生物学意义:MutT也在一定程度上水解四种标准核苷酸,而YbiB不显示这种副反应。因此,YbiB的表达可以在SOS的情况下增加到一个显着更高的水平,而不会对nucleotide pools. Our的目的产生负面影响,我们的目的是详细描述YbiB和其他TrpD 2代表在DNA修复和核苷酸池卫生的背景下的功能。首先,我们将研究8-oxo-dGTP是否是这些酶的主要底物,或者其他受损的核苷酸是否以类似甚至更高的效率转化。此外,我们将测试核酸或蛋白质的结合是否增强YbiB的相对低的活性。此外,我们计划将YbiB与底物类似物和核酸共结晶。所得结构将有助于我们理解TrpD 2蛋白的功能模式。最后,我们将研究磷酸核糖基转移酶III类超家族与其成员TrpD 2,TrpD和NP-II的结构-功能关系。因此,计划中的实验不仅将阐明SOS反应中迄今未知成员的功能,而且还将揭示一个有趣的蛋白质超家族的进化。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Dr. Patrick Babinger其他文献
Dr. Patrick Babinger的其他文献
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{{ truncateString('Dr. Patrick Babinger', 18)}}的其他基金
Archaea-type ether lipids in Bacteria: biosynthesis, processing, and physiological function
细菌中古细菌型醚脂:生物合成、加工和生理功能
- 批准号:
222192502 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Functional annotation of uncharacterized two-substrate enzymes
未表征的双底物酶的功能注释
- 批准号:
108543916 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Research Grants
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