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

Publication ,  Journal Article
Strickland, KC; Hoeferlin, LA; Oleinik, NV; Krupenko, NI; Krupenko, SA
Published in: J Biol Chem
January 15, 2010

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 the FDH-modifying enzyme and supports the hypothesis that mammals utilize a single enzyme for all phosphopantetheinylation reactions.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 15, 2010

Volume

285

Issue

3

Start / End Page

1627 / 1633

Location

United States

Related Subject Headings

  • Transferases (Other Substituted Phosphate Groups)
  • Substrate Specificity
  • Serine
  • RNA, Small Interfering
  • Pantetheine
  • Oxidoreductases Acting on CH-NH Group Donors
  • Humans
  • Gene Silencing
  • Enzyme Activation
  • Cloning, Molecular
 

Citation

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Strickland, K. C., Hoeferlin, L. A., Oleinik, N. V., Krupenko, N. I., & Krupenko, S. A. (2010). Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 285(3), 1627–1633. https://doi.org/10.1074/jbc.M109.080556
Strickland, Kyle C., L Alexis Hoeferlin, Natalia V. Oleinik, Natalia I. Krupenko, and Sergey A. Krupenko. “Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.J Biol Chem 285, no. 3 (January 15, 2010): 1627–33. https://doi.org/10.1074/jbc.M109.080556.
Strickland KC, Hoeferlin LA, Oleinik NV, Krupenko NI, Krupenko SA. Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2010 Jan 15;285(3):1627–33.
Strickland, Kyle C., et al. “Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.J Biol Chem, vol. 285, no. 3, Jan. 2010, pp. 1627–33. Pubmed, doi:10.1074/jbc.M109.080556.
Strickland KC, Hoeferlin LA, Oleinik NV, Krupenko NI, Krupenko SA. Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2010 Jan 15;285(3):1627–1633.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 15, 2010

Volume

285

Issue

3

Start / End Page

1627 / 1633

Location

United States

Related Subject Headings

  • Transferases (Other Substituted Phosphate Groups)
  • Substrate Specificity
  • Serine
  • RNA, Small Interfering
  • Pantetheine
  • Oxidoreductases Acting on CH-NH Group Donors
  • Humans
  • Gene Silencing
  • Enzyme Activation
  • Cloning, Molecular