5F1M

Crystal structure of Serine/threonine phosphatase Stp1 from Staphylococcus aureus

Summary for 5F1M

• Entry DOI: 10.2210/pdb5f1m/pdb
• Descriptor: Phosphorylated protein phosphatase, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: serine/threonine phosphatase 1, hydrolase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 30866.12

Authors

Zheng, W.H.,Wang, T.,Li, Z.G. (deposition date: 2015-11-30, release date: 2016-08-24, Last modification date: 2023-11-08)

Primary citation

Zheng, W.,Cai, X.,Xie, M.,Liang, Y.,Wang, T.,Li, Z.
Structure-Based Identification of a Potent Inhibitor Targeting Stp1-Mediated Virulence Regulation in Staphylococcus aureus
Cell Chem Biol, 23:1002-1013, 2016

PubMed Abstract: The increasing threats of antibiotic resistance urge the need for developing new strategies against bacterial infections. Targeting eukaryotic-like Ser/Thr phosphatase Stp1-mediated virulence regulation represents a promising approach for combating staphylococcal infection yet to be explored. Here, we report the 2.32-Å resolution crystal structure of Stp1. Stp1 binds an unexpected fourth metal ion, which is important for Stp1's enzymatic activity as demonstrated by amino acid substitution studies. Inspired by the structural details of Stp1, we identified a potent and selective Stp1 inhibitor, aurintricarboxylic acid (ATA). Transcriptome analysis and biochemical studies supported Stp1 as the target of ATA inhibition within the pathogen, preventing upregulation of virulence genes. Notably, ATA did not affect in vitro growth of Staphylococcus aureus, while simultaneously attenuating staphylococcal virulence in mice. Our findings demonstrate that ATA is a potent anti-virulence compound against staphylococcal infection, laying the foundation for further developing new scaffolds for Stp1-targeted small molecules.

PubMed: 27499528
DOI: 10.1016/j.chembiol.2016.06.014

Experimental method

X-RAY DIFFRACTION (2.322 Å)