Amino Acids Allosterically Regulate the Thiamine Diphosphate-dependent α-Keto Acid Decarboxylase from Mycobacterium tuberculosis
| Autor: | Stephan König, Michael Spinka, Gerhard Hübner, Kai Tittmann, Ralph Golbik, Tobias Werther, Anja Schütz, Carmen Mrestani-Klaus |
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| Rok vydání: | 2008 |
| Předmět: |
Stereochemistry
Decarboxylation Kinetics Biochemistry 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) Mycobacterium tuberculosis Allosteric Regulation Bacterial Proteins Amino Acids Molecular Biology Gene chemistry.chemical_classification biology food and beverages Cell Biology biology.organism_classification Keto Acids Amino acid Enzyme Activation Enzyme chemistry Thiamine Steady state (chemistry) Thiamine Pyrophosphate |
| Zdroj: | Journal of Biological Chemistry. 283:5344-5354 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m706569200 |
| Popis: | The gene rv0853c from Mycobacterium tuberculosis strain H37Rv codes for a thiamine diphosphate-dependent alpha-keto acid decarboxylase (MtKDC), an enzyme involved in the amino acid degradation via the Ehrlich pathway. Steady state kinetic experiments were performed to determine the substrate specificity of MtKDC. The mycobacterial enzyme was found to convert a broad spectrum of branched-chain and aromatic alpha-keto acids. Stopped-flow kinetics showed that MtKDC is allosterically activated by alpha-keto acids. Even more, we demonstrate that also amino acids are potent activators of this thiamine diphosphate-dependent enzyme. Thus, metabolic flow through the Ehrlich pathway can be directly regulated at the decarboxylation step. The influence of amino acids on MtKDC catalysis was investigated, and implications for other thiamine diphosphate-dependent enzymes are discussed. |
| Databáze: | OpenAIRE |
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