Details

Autor(en) / Beteiligte

• Ma, Pikyee
• Nishiguchi, Kenzo
• Yuille, Hayley M.
• Davis, Lianne M.
• Nakayama, Jiro
• Phillips-Jones, Mary K.

Titel

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

Ist Teil von

• FEBS letters, 2011-09, Vol.585 (17), p.2660-2664

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2011

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• ► 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. 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. PrrB phosphorylates PrrB by protein kinase assay (View interaction) FsrC phosphorylates FsrC by protein kinase assay (View interaction)