标题: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
摘要: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 μM, 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 Nqe6 subunit gradually releases FAD.
关键词:korormicin;2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO);NADH-quinone reductase;sodium ion pump;argentous inhibition;silver