Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes

Chang-Uk Lee, Gernot Hahne, Jonas Hanske, Tanja Bange, David Bier, Christoph Rademacher, Sven Hennig, Tom N Grossmann

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

PTEN is a dual-specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2 O2 ) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.

Original languageEnglish
Pages (from-to)13796-13800
Number of pages5
JournalAngewandte Chemie International Edition in English
Volume54
Issue number46
DOIs
Publication statusPublished - 9 Nov 2015

Keywords

  • bpV-phen
  • disulfides
  • inhibitors
  • protein tyrosine phosphatase
  • tumor suppressors

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