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PDBsum entry 5bug
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References listed in PDB file
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Key reference
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Title
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Redox modulation of pten phosphatase activity by hydrogen peroxide and bisperoxidovanadium complexes.
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Authors
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C.U.Lee,
G.Hahne,
J.Hanske,
T.Bange,
D.Bier,
C.Rademacher,
S.Hennig,
T.N.Grossmann.
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Ref.
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Angew Chem Int Ed Engl, 2015,
54,
13796-13800.
[DOI no: ]
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PubMed id
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Abstract
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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.
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