5BUG

Crystal structure of human phosphatase PTEN oxidized by H2O2

Summary for 5BUG

• Entry DOI: 10.2210/pdb5bug/pdb
• Descriptor: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN, L(+)-TARTARIC ACID (3 entities in total)
• Functional Keywords: hydrolase, c2 domain, disulfide, oxidized
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm. Isoform alpha: Secreted : P60484
• Total number of polymer chains: 4
• Total formula weight: 149831.57

Authors

Lee, C.-U.,Bier, D.,Hennig, S.,Grossmann, T.N. (deposition date: 2015-06-03, release date: 2015-10-07, Last modification date: 2024-10-16)

Primary citation

Lee, C.U.,Hahne, G.,Hanske, J.,Bange, T.,Bier, D.,Rademacher, C.,Hennig, S.,Grossmann, T.N.
Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes.
Angew.Chem.Int.Ed.Engl., 54:13796-13800, 2015

PubMed 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.

PubMed: 26418532
DOI: 10.1002/anie.201506338

Experimental method

X-RAY DIFFRACTION (2.4 Å)