HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase: evidence for a ping-pong mechanism
- 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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| Author: | Andrea EschemannGND, Alexander GalkinORCiD, Walter OettmeierGND, Ulrich BrandtORCiDGND, Stefan Kerscher |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-759055 |
| DOI: | https://doi.org/10.1074/jbc.M411217200 |
| ISSN: | 0021-9258 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/15533932 |
| Parent Title (English): | Journal of biological chemistry |
| Publisher: | American Society for Biochemistry and Molecular Biology Publications |
| Place of publication: | Bethesda, Md |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2021/01/04 |
| Year of first Publication: | 2005 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2023/09/21 |
| Volume: | 280 |
| Issue: | 5 |
| Page Number: | 5 |
| First Page: | 3138 |
| Last Page: | 3142 |
| HeBIS-PPN: | 513164502 |
| Institutes: | Medizin |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - CC BY - Namensnennung 4.0 International |
