title: Triptolide directly inhibits dCTP pyrophosphatase.
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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, P. O. Box 208103, New Haven, CT 06520-8103, USA. tcorson@iupui.edu
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Cavga
authors.forename: Nicholas
authors.initials: N
authors.lastname: Aberle
authors.forename: Craig M
authors.initials: CM
authors.lastname: Crews
mesh_terms: D004247:DNA / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D010616:Phenanthrenes / Q000494:pharmacology*; D019920:Photoaffinity Labels / Q000737:chemistry / Q000378:metabolism; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D019920:Photoaffinity Labels; C001899:triptolide; D004247:DNA; D011755:Pyrophosphatases; C020007:dCTP pyrophosphatase