TY - JOUR
T1 - Anti-HIV siamycin i directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities
AU - Ma, Pikyee
AU - Nishiguchi, Kenzo
AU - Yuille, Hayley M.
AU - Davis, Lianne M.
AU - Nakayama, Jiro
AU - Phillips-Jones, Mary K.
N1 - Funding Information:
We thank Peter J.F. Henderson (University of Leeds) for advice and guidance over many years on expression and purification of membrane proteins. We are grateful to David Sharples for preparations of FsrC-harbouring E. coli membranes in a fermenter facility (University of Leeds). M.K.P.-J. is grateful to the BBSRC ( BB/D001641/1 ) for financial support.
PY - 2011/9/2
Y1 - 2011/9/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.febslet.2011.07.026
DO - 10.1016/j.febslet.2011.07.026
M3 - Article
C2 - 21803040
AN - SCOPUS:80052263187
SN - 0014-5793
VL - 585
SP - 2660
EP - 2664
JO - FEBS Letters
JF - FEBS Letters
IS - 17
ER -
