2025-04-15 京都工芸繊維大学
<関連情報>
- https://www.kit.ac.jp/2025/04/news250415/
- https://www.kit.ac.jp/wp/wp-content/uploads/2025/04/news250415.pdf
- https://www.nature.com/articles/s41598-025-94981-4
構造解析が示す、抗精神病薬ペンフルリドールによる黄色ブドウ球菌リパーゼの阻害様式 Structural analysis shows the mode of inhibition for Staphylococcus aureus lipase by antipsychotic penfluridol
Julia Kitadokoro,Takatsugu Hirokawa,Masayuki Kamo,Naoki Furubayashi,Yukiko Okuno,Takaaki Hikima,Masaki Yamamoto,Koji Inaka,Katsumi Maenaka,Shigeki Kamitani & Kengo Kitadokoro
Scientific Reports Published:14 April 2025
DOI:https://doi.org/10.1038/s41598-025-94981-4
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.
