SortaseB (SrtB) plays a critical role in Staphylococcus aureus (S. aureus) infections. According\nto the reports in the literature, SrtB can anchor the IsdC to the cell wall to capture iron from the\nhost to achieve a successful invasion. On the other hand, SrtB could also affect the adhesion of S.\naureus to host cells based on previous studies. Here, we report about a novel SrtB inhibitor, coptisine,\na natural compound that does not exhibit antibacterial activity but can inhibit the SrtB activity\nin vitro. A cytotoxicity test indicated that coptisine protects human lung epithelial cells from S. aureus.\nIn addition, coptisine can reduce the adhesion of S. aureus to human lung epithelial cells based on\nthe result of plate colony counting assay. Molecular dynamics simulation revealed that coptisine\ncan bind to the active pocket of SrtB, leading to its activity loss. Through the calculation of binding\nfree energy between ligand and protein, site-directed mutagenesis and fluorescence spectroscopy\nquenching methods, it was confirmed that residues of Arg115, Asn116, and Ile182 played a vital\nrole in the interaction of SrtB with coptisine. These data provide the theoretical basis for the therapy\noption to the infections caused by S. aureus
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