Department of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
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).
过氧化氢是一种细胞信号转导剂，通过氧化其催化半胱氨酸残基来使蛋白酪氨酸磷酸酶（PTPs）失活。在 H2O2 介导的细胞信号转导过程中，PTPs 会迅速失活，但矛盾的是，过氧化氢在体外是一种相当缓慢的 PTP 失活剂。在这里，我们提供的证据表明，生物缓冲剂碳酸氢盐/CO2 增强了 H2O2 使 PTP 失活的能力。生化实验和高分辨率晶体学分析的结果与一种机制一致，该机制涉及通过 H2O2 与 HCO3（-）/ CO2 的反应生成的过氧单碳酸盐氧化催化半胱氨酸残基。
