Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.

The Journal of Biological Chemistry
Kyle C StricklandSergey A Krupenko

Abstract

4'-Phosphopantetheinyl transferases (PPTs) catalyze the transfer of 4'-phosphopantetheine (4-PP) from coenzyme A to a conserved serine residue of their protein substrates. In humans, the number of pathways utilizing the 4-PP post-translational modification is limited and may only require a single broad specificity PPT for all phosphopantetheinylation reactions. Recently, we have shown that one of the enzymes of folate metabolism, 10-formyltetrahydrofolate dehydrogenase (FDH), requires a 4-PP prosthetic group for catalysis. This moiety acts as a swinging arm to couple the activities of the two catalytic domains of FDH and allows the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. In the current study, we demonstrate that the broad specificity human PPT converts apo-FDH to holoenzyme and thus activates FDH catalysis. Silencing PPT by small interfering RNA in A549 cells prevents FDH modification, indicating the lack of alternative enzymes capable of accomplishing this transferase reaction. Interestingly, PPT-silenced cells demonstrate significantly reduced proliferation and undergo strong G(1) arrest, suggesting that the enzymatic function of PPT is essential and nonredundant. Our study identifies human PPT as...Continue Reading

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Citations

May 26, 2010·The Journal of Biological Chemistry·Natalia I KrupenkoSergey A Krupenko
Sep 25, 2015·The Plant Journal : for Cell and Molecular Biology·Xin GuanBasil J Nikolau
Jan 18, 2011·Chemico-biological Interactions·Kyle C StricklandSergey A Krupenko
Jan 1, 2015·Chemico-biological Interactions·Natalia I KrupenkoSergey A Krupenko
Nov 9, 2019·EMBO Molecular Medicine·Roald A LambrechtsOdy Cm Sibon
Nov 19, 2019·Frontiers in Genetics·Sergey A Krupenko, David A Horita
Feb 23, 2019·Chemico-biological Interactions·Sergey A Krupenko, Natalia I Krupenko

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