Anti-HIV siamycin I directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities

作者：Ma Pikyee; Nishiguchi Kenzo; Yuille Hayley M; Davis Lianne M; Nakayama Jiro; Phillips Jones Mary K^*

来源：FEBS Letters, 2011, 585(17): 2660-2664.

DOI：10.1016/j.febslet.2011.07.026

• Bacterial two-component signal transduction system
• FsrC
• Quorum sensing
• Siamycin I
• HIV inhibitor
• Enterococcus faecalis

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 noncompetitive 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 beta-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 interactions:
PrrB phosphorylates PrrB by protein kinase assay (View interaction) <br&

• 出版日期2011-9-2