| Title: | Anti-HIV siamycin I directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities |
| Author(s): | Ma P; Nishiguchi K; Yuille HM; Davis LM; Nakayama J; Phillips-Jones MK; |
| Address: | "Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom" |
| DOI: | 10.1016/j.febslet.2011.07.026 |
| ISSN/ISBN: | 1873-3468 (Electronic) 0014-5793 (Linking) |
| 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 beta-galactosidase, confirming targeted inhibition of a wide range of ATP dependent reactions, and elucidating a likely mechanism underlying the lethality of the inhibitor" |
| Keywords: | Adenosine Triphosphatases/metabolism Animals Bacterial Proteins/*metabolism Cattle Enterococcus faecalis/drug effects/*metabolism Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology Intercellular Signaling Peptides and Proteins Kinetics Microbia; |
| Notes: | "MedlineMa, Pikyee Nishiguchi, Kenzo Yuille, Hayley M Davis, Lianne M Nakayama, Jiro Phillips-Jones, Mary K eng BB/D001641/1/Biotechnology and Biological Sciences Research Council/United Kingdom Research Support, Non-U.S. Gov't England 2011/08/02 FEBS Lett. 2011 Sep 2; 585(17):2660-4. doi: 10.1016/j.febslet.2011.07.026. Epub 2011 Jul 26" |
