The structural mechanism for the nucleoside tri- and diphosphate hydrolysis activity of Ntdp from Staphylococcus aureus

Staphylococcus aureus is a well-known clinical pathogenic bacterium. In recent years, due to the emergence of multiple drug-resistant strains of S. aureus in clinical practice, S. aureus infections have become an increasingly severe clinical problem. Ntdp (nucleoside tri- and diphosphatase, also known as Sa1684) is a nucleotide phosphatase that has a significant effect on the proliferation of S. aureus colonies 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 (ATP(gamma)S, GDP(beta)S, and GTP(gamma)S) 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 factor agr and the downstream virulence factors. Overall, the above findings provide crucial insights into our understanding of the Ntdp functional mechanism in the infection process.

Automated summary

Staphylococcus aureus infections have become a serious clinical problem due to the emergence of drug-resistant strains in recent years. The nucleotide phosphatase Ntdp plays a crucial role in the infection process. Through structural and biochemical studies, insights into the catalytic mechanism and regulatory pathways of Ntdp have been revealed.