The Biological Buffer Bicarbonate/CO2 Potentiates H2O2-Mediated Inactivation of Protein Tyrosine Phosphatases

• Published in: Journal of the American Chemical Society Vol. 133; no. 40; pp. 15803 - 15805
• Main Authors: Zhou, Haiying, Singh, Harkewal, Parsons, Zachary D, Lewis, Sarah M, Bhattacharya, Sanjib, Seiner, Derrick R, LaButti, Jason N, Reilly, Thomas J, Tanner, John J, Gates, Kent S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12-10-2011
• Subjects: Bicarbonates - metabolism; Buffers; Carbon Dioxide - metabolism; Enzyme Activation; Humans; Hydrogen Peroxide - metabolism; Models, Molecular; Oxidation-Reduction; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja2077137

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 H2O2-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/CO2 potentiates the ability of H2O2 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 H2O2 with HCO3 –/CO2.