Inhibitor studies of a new antibiotic, korormicin, 2-n-heptyl-4-hydroxyquinoline N-oxide and Ag+ toward the Na+-translocating NADH-quinone reductase from the marine Vibrio alginolyticus.
A new antibiotic, korormicin, isolated from a marine bacterium Pseudoalteromonas sp. F-420, was found to strongly inhibit the respiratory chain-linked Na+-translocating NADH-quinone reductase (NQR) from the marine Vibrio alginolyticus. Similar to 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), korormicin specifically inhibited the Na+-dependent reaction in the NQR complex that is directly coupled to the extrusion of Na+ from the cells. Both korormicin and HQNO acted as purely noncompetitive inhibitors with regard to Q-1, and the inhibitor constants were estimated to be 82 pM and 0.3 microM, respectively. Mutual exclusiveness of korormicin and HQNO was analyzed by kinetic methods, which indicated that a part of the binding site of korormicin and HQNO overlapped, preventing a simultaneous binding of the two inhibitors to the NQR complex. The site of Ag+ inhibition was the initial reaction of the NQR complex catalyzed by Nqr6 subunit. The time courses of Ag+ inhibition and the release of FAD indicate that the Ag+-denatured Nqr6 subunit gradually releases FAD.
Nakayama
Y
Y
Laboratory of Membrane Biochemistry, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Hayashi
M
M
Yoshikawa
K
K
Mochida
K
K
Unemoto
T
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D009245:NADH Dehydrogenase / Q000378:metabolism; D011808:Quinone Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012834:Silver / Q000494:pharmacology; D014733:Vibrio / Q000187:drug effects / Q000201:enzymology*; D014871:Water Microbiology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006912:Hydroxyquinolines; D007783:Lactones; C111296:korormicin; C001333:2-(n-heptyl)-4-hydroxyquinoline N-oxide; D012834:Silver; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D009245:NADH Dehydrogenase