title: Inactivation of Protein Tyrosine Phosphatases by Peracids Correlates with the Hydrocarbon Chain Length.
abstract: OBJECTIVE
  Protein tyrosine phosphatases are crucial enzymes controlling numerous physiological and pathophysiological events and can be regulated by oxidation of the catalytic domain cysteine residue. Peracids are highly oxidizing compounds, and thus may induce inactivation of PTPs. The aim of the present study was to evaluate the inhibitory effect of peracids with different length of hydrocarbon chain on the activity of selected PTPs.
  
  
  METHODS
  The enzymatic activity of human CD45, PTP1B, LAR, bacterial YopH was assayed under the cell-free conditions, and activity of cellular CD45 in human Jurkat cell lysates. The molecular docking and molecular dynamics were performed to evaluate the peracids binding to the CD45 active site.
  
  
  RESULTS
  Here we demonstrate that peracids reduce enzymatic activity of recombinant CD45, PTP1B, LAR, YopH and cellular CD45. Our studies indicate that peracids are more potent inhibitors of CD45 than hydrogen peroxide (with an IC50 value equal to 25 nM for peroctanoic acid and 8 µM for hydrogen peroxide). The experimental data show that the inactivation caused by peracids is dependent on hydrocarbon chain length of peracids with maximum inhibitory effect of medium-chain peracids (C8-C12 acyl chain), which correlates with calculated binding affinities to the CD45 active site.
  
  
  CONCLUSIONS
  Peracids are potent inhibitors of PTPs with the strongest inhibitory effect observed for medium-chain peracids.
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Kuban-Jankowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gorska
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
authors.forename: Cassandra D M
authors.initials: CD
authors.lastname: Churchill
authors.forename: Philip
authors.initials: P
authors.lastname: Winter
authors.forename: Mariusz
authors.initials: M
authors.lastname: Klobukowski
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D002457:Cell Extracts / Q000737:chemistry; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D019169:Jurkat Cells; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000037:antagonists & inhibitors* / Q000737:chemistry; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010463:Peracetic Acid / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002457:Cell Extracts; D004791:Enzyme Inhibitors; D010545:Peroxides; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; C067571:yopH protein, Yersinia; D010463:Peracetic Acid