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Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes
- Source :
- Angewandte Chemie International Edition in English, 54(46), 13796-13800. John Wiley and Sons Ltd, Angewandte Chemie (International Ed. in English), Lee, C-U, Hahne, G, Hanske, J, Bange, T, Bier, D, Rademacher, C, Hennig, S & Grossmann, T N 2015, ' Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes ', Angewandte Chemie International Edition in English, vol. 54, no. 46, pp. 13796-13800 . https://doi.org/10.1002/anie.201506338
- Publication Year :
- 2015
- Publisher :
- John Wiley and Sons Ltd, 2015.
-
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.
- Subjects :
- Models, Molecular
bpV-phen
disulfides
Cellular homeostasis
Protein tyrosine phosphatase
Oxidative phosphorylation
protein tyrosine phosphatase
Catalysis
law.invention
Structure-Activity Relationship
Phosphatase Inhibition
SDG 3 - Good Health and Well-being
law
inhibitors
Organometallic Compounds
Humans
Structure–activity relationship
PTEN
Mode of action
chemistry.chemical_classification
Reactive oxygen species
Dose-Response Relationship, Drug
Molecular Structure
biology
tumor suppressors
Chemistry
PTEN Phosphohydrolase
Vanadium
Hydrogen Peroxide
General Chemistry
Communications
Peroxides
Biochemistry
biology.protein
Suppressor
Oxidation-Reduction
Subjects
Details
- Language :
- English
- ISSN :
- 05700833
- Volume :
- 54
- Issue :
- 46
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition in English
- Accession number :
- edsair.doi.dedup.....fa5f02c18a719e632bdfa8ffe985fa6c
- Full Text :
- https://doi.org/10.1002/anie.201506338