HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase

A. Eschemann, Alexander Galkin, W. Oettmeier, U. Brandt, S. Kerscher

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3138-3142
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
Publication statusPublished - 04 Feb 2005

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NADH Dehydrogenase
Electron Transport Complex I
Ubiquinone
NAD
Yarrowia
Electron Transport
Mitochondria
Kinetics
Membrane Proteins
Bacteria
Enzymes
1-hydroxy-2-dodecyl-4(1H)quinolone
Substrates

Cite this

Eschemann, A. ; Galkin, Alexander ; Oettmeier, W. ; Brandt, U. ; Kerscher, S. / HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 5. pp. 3138-3142.
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HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase. / Eschemann, A.; Galkin, Alexander; Oettmeier, W.; Brandt, U.; Kerscher, S.

In: Journal of Biological Chemistry, Vol. 280, No. 5, 04.02.2005, p. 3138-3142.

Research output: Contribution to journalArticle

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T1 - HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase

AU - Eschemann, A.

AU - Galkin, Alexander

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AU - Kerscher, S.

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AB - 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.

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