The structural mechanism for the nucleoside tri- and diphosphate hydrolysis activity of Ntdp from Staphylococcus aureus
The structural mechanism for the nucleoside tri- and diphosphate hydrolysis activity of Ntdp from Staphylococcus aureus
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DOI：
10.1111/febs.15911
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发表时间：
2021-06-10
期刊：
影响因子：
5.4
通讯作者：
Li，Xu
中科院分区：
文献类型：
--
作者：
Wang，Zhenhua;Shen，Hui;Li，Xu
金黄色葡萄球菌是临床常见的致病菌。近年来，由于OFS多重耐药菌株的出现。在临床实践中，金黄色葡萄球菌感染已成为日益严峻的临床问题。NTDP(核苷三二磷酸酶，又称SA1684)是一种核苷酸磷酸酶，对金黄色葡萄球菌的增殖和宿主的杀伤能力有重要影响。在这里，我们鉴定了NTDP的核苷三磷酸和二磷酸的水解活性，并获得了NTDP的apo-NTDP和三种底物类似物(三磷酸腺苷γS、国内生产总值βS和三磷酸鸟苷γS)的三维结构。通过结构分析和生化验证，阐明了NTDP二价阳离子选择性的结构基础、底物识别模型和催化机理。我们还揭示了DUF402结构域可能的基本功能模式，并假设了该蛋白调节双组分调控因子和下游毒力因子表达的潜在途径。总体而言，上述发现为我们理解NTDP在感染过程中的作用机制提供了至关重要的见解。
Staphylococcus aureusis a well‐known clinical pathogenic bacterium. In recent years, due to the emergence of multiple drug‐resistant strains ofS. aureusin clinical practice,S. aureusinfections have become an increasingly severe clinical problem. Ntdp (nucleoside tri‐ and diphosphatase, also known asSa1684) is a nucleotide phosphatase that has a significant effect on the proliferation ofS. aureuscolonies and the killing ability of the host. Here, we identified the nucleoside tri‐ and diphosphate hydrolysis activity of Ntdp and obtained the three‐dimensional structures of apo‐Ntdp and three substrate analog (ATPγS, GDPβS, and GTPγS) complexes of Ntdp. Through structural analysis and biochemical verification, we illustrated the structural basis for the divalent cation selectivity, substrate recognition model, and catalytic mechanism of Ntdp. We also revealed a possible basal functional pattern of the DUF402 domain and hypothesized the potential pathways by which the protein regulates the expression of the two‐component regulatory factoragrand the downstream virulence factors. Overall, the above findings provide crucial insights into our understanding of the Ntdp functional mechanism in the infection process.