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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2660-2664
Number of pages5
JournalFEBS Letters
Volume585
Issue number17
DOIs
Publication statusPublished - Sep 2 2011

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Enzyme activity
Adenosine Triphosphate
Enterococcus faecalis
HIV
Sensors
Phosphotransferases
Enzymes
Galactosidases
Membranes
Rhodobacter sphaeroides
Quorum Sensing
Pheromones
Cyclic AMP-Dependent Protein Kinases
Adenosine Triphosphatases
Catalytic Domain
Swine
Substrates
Growth
Proteins
siamycin I

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Anti-HIV siamycin i directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities. / Ma, Pikyee; Nishiguchi, Kenzo; Yuille, Hayley M.; Davis, Lianne M.; Nakayama, Jiro; Phillips-Jones, Mary K.

In: FEBS Letters, Vol. 585, No. 17, 02.09.2011, p. 2660-2664.

Research output: Contribution to journalArticle

Ma, Pikyee ; Nishiguchi, Kenzo ; Yuille, Hayley M. ; Davis, Lianne M. ; Nakayama, Jiro ; Phillips-Jones, Mary K. / Anti-HIV siamycin i directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities. In: FEBS Letters. 2011 ; Vol. 585, No. 17. pp. 2660-2664.
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