Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes. Issue 46 (29th September 2015)

• Record Type: Journal Article
• Authors: Lee, Chang‐Uk; Hahne, Gernot; Hanske, Jonas; Bange, Tanja; Bier, David; Rademacher, Christoph; Hennig, Sven; Grossmann, Tom N.
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 46(2015)
• Page Start: 13796
• Page End: 13800
• Publication Date: 2015-09-29
• Subjects: bpV‐phen -- disulfides -- inhibitors -- protein tyrosine phosphatase -- tumor suppressors; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201506338
• Languages: English
• ISSNs: 1433-7851

Abstract

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 H2 O2 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. Abstract : An important tumor suppressor, the phosphatase PTEN, is crucially involved in regenerative processes. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, the molecular basis of PTEN inhibition by H2 O2 and bisperoxidovanadium complexes has been elucidated. Both inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.