Diverse mechanisms of inhibition of pyruvate dehydrogenase kinase by structurally distinct inhibitors
| Autor: | Carol J. Dragland, William R. Mann, Philip A. Bell, T.R Vedananda, Thomas Daniel Aicher, Christine C. Vinluan |
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| Rok vydání: | 2000 |
| Předmět: |
Pyruvate decarboxylation
Pyruvate dehydrogenase lipoamide kinase isozyme 1 Pyruvate dehydrogenase kinase Biophysics Pyruvate dehydrogenase phosphatase Protein Serine-Threonine Kinases Biochemistry law.invention Structural Biology law medicine Enzyme Inhibitors Phosphorylation Molecular Biology Protein Kinase Inhibitors Molecular Structure Chemistry Autophosphorylation Pyruvate Dehydrogenase Acetyl-Transferring Kinase Pyruvate dehydrogenase complex Mechanism of action Recombinant DNA Electrophoresis Polyacrylamide Gel medicine.symptom Protein Kinases |
| Zdroj: | Biochimica et biophysica acta. 1480(1-2) |
| ISSN: | 0006-3002 |
| Popis: | The mechanism of action of structurally distinct pyruvate dehydrogenase kinase (PDK) inhibitors was examined in assays with experimental contexts ranging from an intact pyruvate dehydrogenase complex (PDC) with and without supplemental ATP or ADP to a synthetic peptide substrate to PDK autophosphorylation. Some compounds directly inhibited the catalytic activity of PDKs. Some of the inhibitor classes tested inhibited autophosphorylation of recombinant PDK1 and PDK2. During these studies, PDC was shown to be directly inhibited by a novel mechanism; the addition of supplemental recombinant PDKs, an effect that is ADP-dependent and partly alleviated by members of each of the compound classes tested. Overall, these data demonstrate that small molecules acting at diverse sites can inhibit PDK activity. |
| Databáze: | OpenAIRE |
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