title: HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase: evidence for a ping-pong mechanism.
abstract: Alternative NADH dehydrogenases (NADH:ubiquinone oxidoreductases) are single subunit respiratory chain enzymes found in plant and fungal mitochondria and in many bacteria. It is unclear how these peripheral membrane proteins interact with their hydrophobic substrate ubiquinone. Known inhibitors of alternative NADH dehydrogenases bind with rather low affinities. We have identified 1-hydroxy-2-dodecyl-4(1H)quinolone as a high affinity inhibitor of alternative NADH dehydrogenase from Yarrowia lipolytica. Using this compound, we have analyzed the bisubstrate and inhibition kinetics for NADH and decylubiquinone. We found that the kinetics of alternative NADH dehydrogenase follow a ping-pong mechanism. This suggests that NADH and the ubiquinone headgroup interact with the same binding pocket in an alternating fashion.
authors.affiliation: Universität Frankfurt, Fachbereich Medizin, Institut für Biochemie I, Frankfurt am Main D-60490, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Eschemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Galkin
authors.forename: Walter
authors.initials: W
authors.lastname: Oettmeier
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.forename: Stefan
authors.initials: S
authors.lastname: Kerscher
mesh_terms: D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004583:Electrons; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008956:Models, Chemical; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism*; D025062:Yarrowia / Q000201:enzymology*
chemical_list: D015363:Quinolones; D042967:Electron Transport Complex I