The biological buffer bicarbonate/CO2 potentiates H2O2-mediated inactivation of protein tyrosine phosphatases

J Am Chem Soc. 2011 Oct 12;133(40):15803-5. doi: 10.1021/ja2077137. Epub 2011 Sep 19.


Hydrogen peroxide is a cell signaling agent that inactivates protein tyrosine phosphatases (PTPs) via oxidation of their catalytic cysteine residue. PTPs are inactivated rapidly during H(2)O(2)-mediated cellular signal transduction processes, but, paradoxically, hydrogen peroxide is a rather sluggish PTP inactivator in vitro. Here we present evidence that the biological buffer bicarbonate/CO(2) potentiates the ability of H(2)O(2) to inactivate PTPs. The results of biochemical experiments and high-resolution crystallographic analysis are consistent with a mechanism involving oxidation of the catalytic cysteine residue by peroxymonocarbonate generated via the reaction of H(2)O(2) with HCO(3)(-)/CO(2).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bicarbonates / metabolism*
  • Buffers
  • Carbon Dioxide / metabolism*
  • Enzyme Activation
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*


  • Bicarbonates
  • Buffers
  • Carbon Dioxide
  • Hydrogen Peroxide
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1