title: Amino acids allosterically regulate the thiamine diphosphate-dependent alpha-keto acid decarboxylase from Mycobacterium tuberculosis.
abstract: 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.
authors: Institute of Biochemistry and Biotechnology, Faculty for Biological Sciences, Martin-Luther-University Halle-Wittenberg, 06120 Halle Saale, Germany.
authors: Tobias
authors: T
authors: Werther
authors: Michael
authors: M
authors: Spinka
authors: Kai
authors: K
authors: Tittmann
authors: Anja
authors: A
authors: Schütz
authors: Ralph
authors: R
authors: Golbik
authors: Carmen
authors: C
authors: Mrestani-Klaus
authors: Gerhard
authors: G
authors: Hübner
authors: Stephan
authors: S
authors: König
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism*; D000494:Allosteric Regulation / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D007651:Keto Acids / Q000378:metabolism; D007700:Kinetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D007651:Keto Acids; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D013835:Thiamine Pyrophosphate