9L3S | pdb_00009l3s

Structural analysis shows the mode of inhibition for Staphylococcus aureus lipase by antipsychotic penfluridol.

(2025) Sci Rep 15: 11876-11876

• PubMed: 40229318 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/s41598-025-94981-4
• Primary Citation of Related Structures:  
  9L3C, 9L3S


• PubMed Abstract: 
  

  It is now well-established that Staphylococcus aureus can produce a range of toxin proteins, resulting in a spectrum of pathological conditions when it infects individuals with pre-existing medical conditions or immunocompromised. Among these, MRSA is one of the most prominent antimicrobial-resistant organisms and a significant cause of mortality in many patients. It has been demonstrated that Staphylococcus aureus lipase (SAL) is a vital factor in the proliferation of this bacterium. A combination of in silico screening and X-ray crystallography was employed to analyze inhibitors of SAL, and the results were highly significant. In silico screening identified a number of compounds, and the enzyme activity assay demonstrated that the antipsychotic drug penfluridol exhibited potent inhibitory activity against SAL. We have conducted co-crystallization of penfluridol and SAL on the ground and in space. The resulting co-crystals were subjected to data measurement using the synchrotron radiation facility at SPring-8, and the complex structure was determined. The crystal structure of the penfluridol-SAL complex was determined at 2.2 Å resolution, thereby providing the structural basis for developing new anti-infective agents that inhibit the growth of Staphylococcus aureus. These findings are anticipated to facilitate the development of compounds with potent inhibitory activity.

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Organizational Affiliation: 

Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Hashigami-cho, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.