PDH activation
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Despite an improvement of prognosis in breast and colon cancer, the outcome of the metastatic disease is still severe. Microevolution of cancer cells often leads to drug resistance and tumor-recurrence. To target the driving forces of the tumor microevolution, we focused on synergistic drug combinations of selected compounds.
14p vidhaka2711 31-07-2020 10 2 Download
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Limitedproteolysis of the pyruvate decarboxylase (E1,a2b2 ) component of the pyruvate dehydrogenase (PDH) multi-enzyme complexofBacillus stearothermophilushas indicated the importance for catalysis of a site (Tyr281-Arg282) in the E1asubunit (Chauhan, H.J., Domingo, G.J., Jung, H.-I. & Perham, R.N. (2000)Eur. J. Biochem.267, 7158–7169). This site appears to be conserved in the a-subunit of hetero-tetrameric E1s and multiple sequence alignments suggest that there are additional conserved amino-acid residues in this region, part of a common pattern with the consensus sequence -YR-H-D-YR-DE-.
10p tumor12 20-04-2013 52 2 Download
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The Escherichia coli bifunctional T-protein transforms chorismic acid to p-hydroxyphenylpyruvic acid in the L-tyrosine biosynthetic pathway. The 373 amino acid T-protein is a homodimer that exhibits chorismate mutase (CM) and prephenate dehydrogenase (PDH) activities, both of which are feedback-inhibited by tyrosine. Fifteen genes coding for the T-protein and various fragments thereof were constructed and successfully expressed in order to charac-terize theCM, PDHand regulatory domains.
7p tumor12 20-04-2013 33 1 Download