title: The biological buffer bicarbonate/CO2 potentiates H2O2-mediated inactivation of protein tyrosine phosphatases.
abstract: 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).
authors.affiliation: Department of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhou
authors.forename: Harkewal
authors.initials: H
authors.lastname: Singh
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Parsons
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Lewis
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Derrick R
authors.initials: DR
authors.lastname: Seiner
authors.forename: Jason N
authors.initials: JN
authors.lastname: LaButti
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Reilly
authors.forename: John J
authors.initials: JJ
authors.lastname: Tanner
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
mesh_terms: D001639:Bicarbonates / Q000378:metabolism*; D002021:Buffers; D002245:Carbon Dioxide / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D002021:Buffers; D002245:Carbon Dioxide; D006861:Hydrogen Peroxide; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1