Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase

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

Research output: Contribution to journalArticle

50 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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