5BUG: Crystal Structure Of Human Phosphatase Pten Oxidized By H2o2

Citation:
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.
PDB ID: 5BUGDownload
MMDB ID: 134183
PDB Deposition Date: 2015/6/3
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 5BUG: monomeric; determined by author
Molecular Components in 5BUG
Label Count Molecule
Protein (1 molecule)
1
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and Dual-specificity Protein Phosphatase Pten(Gene symbol: PTEN)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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