Activation of Hydrogen Peroxide to Peroxytetradecanoic Acid Is Responsible for Potent Inhibition of Protein Tyrosine Phosphatase CD45
نویسندگان
چکیده
Hydrogen peroxide induces oxidation and consequently inactivation of many protein tyrosine phosphatases. It was found that hydrogen peroxide, in the presence of carboxylic acids, was efficiently activated to form even more potent oxidant - peroxy acid. We have found that peroxytetradecanoic acid decreases the enzymatic activity of CD45 phosphatase significantly more than hydrogen peroxide. Our molecular docking computational analysis suggests that peroxytetradecanoic acid has a higher binding affinity to the catalytic center of CD45 than hydrogen peroxide.
منابع مشابه
Inhibition of protein tyrosine phosphatase by the antitumor agent gallium nitrate.
Protein tyrosine phosphatases (PTPases) play an important role in regulating cell growth and transformation. We report that the antitumor agent gallium nitrate is a potent inhibitor (concentration producing 50% inhibition, 2-6 microM) of detergent-solubilized cellular membrane PTPase from Jurkat human T-cell leukemia cells and HT-29 human colon cancer cells. This is the first report of a select...
متن کاملActivation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation.
Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular subst...
متن کاملCharacterization of the reversible phosphorylation and activation of ERK8.
ERK8 (extracellular-signal-regulated protein kinase 8) expressed in Escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the Thr-Glu-Tyr motif. Dephosphorylation of the threonine residue by PP2A (protein serine/threonine phosphatase 2A) decreased ERK8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by PTP1B (p...
متن کاملStructural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45
CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of huma...
متن کاملPartial characterization of the CD45 phosphatase cDNA in the owl monkey (Aotus vociferans).
CD45 is a protein tyrosine phosphatase implicated in T and B cell activation, differentiation, and development. It dephosphorylates specific tyrosine residues on its substrates, principally on the Src-family of protein tyrosine kinases, thus regulating T cell or B cell activation during the immune response. In this study, we present the partial CD45 nucleotide and deduced amino-acid sequences f...
متن کامل