Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase

Andrew J. Wiemer, Huaxiang Tong, Kelly M. Swanson, Raymond Hohl

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

A primary cellular target of the clinical nitrogenous bisphosphonates is the isoprenoid biosynthetic pathway. Specifically these drugs inhibit the enzyme farnesyl pyrophosphate synthase and deplete cells of larger isoprenoids. Inhibition of this enzyme results in impaired processing of both farnesylated and geranylgeranylated proteins. We recently showed that isoprenoid-containing bisphosphonates such as digeranyl bisphosphonate inhibit protein geranylgeranylation and not farnesylation. Here, we show that this impairment results from potent and specific inhibition of geranylgeranyl pyrophosphate synthase, which leads to enhanced depletion of intracellular geranylgeranyl pyrophosphate relative to the nitrogenous bisphosphonate zoledronate.

Original languageEnglish (US)
Pages (from-to)921-925
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume353
Issue number4
DOIs
StatePublished - Feb 23 2007

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Geranylgeranyl-Diphosphate Geranylgeranyltransferase
Terpenes
Diphosphonates
zoledronic acid
Protein Prenylation
Prenylation
Biosynthetic Pathways
Enzymes
Proteins
Processing
Pharmaceutical Preparations
digeranyl bisphosphonate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Wiemer, Andrew J. ; Tong, Huaxiang ; Swanson, Kelly M. ; Hohl, Raymond. / Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 353, No. 4. pp. 921-925.
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Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. / Wiemer, Andrew J.; Tong, Huaxiang; Swanson, Kelly M.; Hohl, Raymond.

In: Biochemical and Biophysical Research Communications, Vol. 353, No. 4, 23.02.2007, p. 921-925.

Research output: Contribution to journalArticle

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