Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
FEBS Lett. 2011 Sep 2;585(17):2660-4. doi: 10.1016/j.febslet.2011.07.026. Epub 2011 Jul 26.
Siamycin I disrupts growth and quorum sensing in Enterococcus faecalis. Using purified intact protein, we demonstrate here that quorum membrane sensor kinase FsrC is a direct target of siamycin I, reducing pheromone-stimulated autophosphorylation activity by up to 91%. Inhibition was non-competitive with ATP as substrate. Other ATP-binding enzymes were also inhibited, including nine other membrane sensor kinases of E. faecalis, Rhodobacter sphaeroides PrrB, porcine Na(+)-dependent ATPase and the catalytic subunit of bovine protein kinase A, but not bacterial β-galactosidase, confirming targeted inhibition of a wide range of ATP dependent reactions, and elucidating a likely mechanism underlying the lethality of the inhibitor.
西马霉素 I 可破坏粪肠球菌的生长和群体感应。在这里，我们使用纯化的完整蛋白证明，群体感应膜传感器激酶 FsrC 是西马霉素 I 的直接靶标，使信息素刺激的自动磷酸化活性降低高达 91%。抑制作用是非竞争性的，底物为 ATP。其他与 ATP 结合的酶也受到抑制，包括粪肠球菌的其他 9 种膜传感器激酶、球形红杆菌 PrrB、猪钠依赖性 ATP 酶和牛蛋白激酶 A 的催化亚基，但不包括细菌β-半乳糖苷酶，这证实了对广泛的 ATP 依赖反应的靶向抑制，并阐明了抑制剂的致死作用的可能机制。
