Gramicidin S identified as a potent inhibitor for cytochrome bd-type quinol oxidase.
Gramicidin S, a cationic cyclic decapeptide, exhibits the potent antibiotic activity through perturbation of lipid bilayers of the bacterial membrane. From the screening of natural antibiotics, we identified gramicidin S as a potent inhibitor for cytochrome bd-type quinol oxidase from Escherichia coli. We found that gramicidin S inhibited the oxidase with IC(50) of 3.5 microM by decreasing V(max) and the affinity for substrates but showed the stimulatory effect at low concentrations. Our findings would provide a new insight into the development of gramicidin S analogs, which do not share the target and mechanism with conventional antibiotics.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. tmogi@m.u-tokyo.ac.jp
Tatsushi
T
Mogi
Hideaki
H
Ui
Kazuro
K
Shiomi
Satoshi
S
Omura
Kiyoshi
K
Kita
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003573:Cytochrome b Group; D003580:Cytochromes / Q000037:antagonists & inhibitors*; D003902:Detergents / Q000737:chemistry; D045222:Electron Transport Chain Complex Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D006096:Gramicidin / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008823:Micelles; D008956:Models, Chemical; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D003573:Cytochrome b Group; D003580:Cytochromes; D003902:Detergents; D045222:Electron Transport Chain Complex Proteins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D008823:Micelles; D006096:Gramicidin; D010088:Oxidoreductases; C040077:cytochrome bd terminal oxidase complex, E coli