Triptolide Directly Inhibits dCTP Pyrophosphatase

Timothy Corson, Hüseyin Cavga, Nicholas Aberle, Craig M. Crews

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide. Nucleotide denied by triptolide: Using a photoaffinity pull-down approach, we found that the natural product triptolide binds to and inhibits the function of dCTP pyrophosphatase (DCTPP1; see scheme). Triptolide will be a useful tool for probing the function of this newly characterized metabolic enzyme.

Original languageEnglish
Pages (from-to)1767-1773
Number of pages7
JournalChemBioChem
Volume12
Issue number11
DOIs
StatePublished - Jul 25 2011

Fingerprint

Biological Products
dCTP pyrophosphatase
triptolide
Proteins
Kidney Diseases
Immunosuppressive Agents
Anti-Inflammatory Agents
Nucleotides
Derivatives
Enzymes

Keywords

  • DCTPP1
  • Natural products
  • Nucleotides
  • Photoaffinity labeling
  • Triptolide

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Triptolide Directly Inhibits dCTP Pyrophosphatase. / Corson, Timothy; Cavga, Hüseyin; Aberle, Nicholas; Crews, Craig M.

In: ChemBioChem, Vol. 12, No. 11, 25.07.2011, p. 1767-1773.

Research output: Contribution to journalArticle

Corson, T, Cavga, H, Aberle, N & Crews, CM 2011, 'Triptolide Directly Inhibits dCTP Pyrophosphatase', ChemBioChem, vol. 12, no. 11, pp. 1767-1773. https://doi.org/10.1002/cbic.201100007
Corson, Timothy ; Cavga, Hüseyin ; Aberle, Nicholas ; Crews, Craig M. / Triptolide Directly Inhibits dCTP Pyrophosphatase. In: ChemBioChem. 2011 ; Vol. 12, No. 11. pp. 1767-1773.
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