Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2047942 | FEBS Letters | 2011 | 5 Pages |
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.Structured summary of protein interactionsPrrBphosphorylatesPrrB by protein kinase assay(View interaction)FsrCphosphorylatesFsrC by protein kinase assay(View interaction)
► Quorum membrane sensor kinase FsrC is a direct target of siamycin I. ► Both GBAP-activated and non-activated FsrC activity is inhibited. ► Inhibition of FsrC by siamycin I is non-competitive with ATP substrate. ► Other membrane sensor kinases and ATP-binding enzymes from a range of sources are also inhibited, demonstrating targeted inhibition of ATP-dependent reactions. ► The likely mechanism underlying the lethality of the inhibitor has been elucidated.