Monteiro Gisele, Horta Bruno B, Pimenta Daniel Carvalho, Augusto Ohara, Netto Luis E S
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277, CEP 05508-900, São Paulo, Brazil.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4886-91. doi: 10.1073/pnas.0700481104. Epub 2007 Mar 14.
Peroxiredoxins (Prx) are widely distributed peroxidases that can be divided into 1-Cys and 2-Cys Prx groups based on the number of conserved cysteine residues that participate in their catalytical cycle. Prx have been described to be strictly dependent on thiols, but here, we show that ascorbate (vitamin C) also reduces 1-Cys Prx, but not 2-Cys Prx, from several taxonomic groups. Reduction by ascorbate is partly related to the fact that the oxidized form of 1-Cys Prx is a stable sulfenic acid (Cys-SOH) instead of a disulfide. In addition, a histidine residue in the active site is required. In fact, we engineered a 2-Cys Prx with these two features, and it displayed ascorbate peroxidase activity. These data represent a breakthrough in the thiol-specific antioxidant paradigm. Ascorbate may be the long-sought-after biological reductant of 1-Cys Prx. Because ascorbate is present in high amounts in cells, the ascorbate/protein sulfenic acid pair represents an aspect of redox biochemistry that has yet to be explored in vivo.
过氧化物酶体增殖物激活受体（Prx）是广泛分布的过氧化物酶，根据参与其催化循环的保守半胱氨酸残基数量可分为1-Cys Prx和2-Cys Prx组。Prx被认为严格依赖于硫醇，但在此我们表明，抗坏血酸（维生素C）也能还原来自几个分类群的1-Cys Prx，而不能还原2-Cys Prx。抗坏血酸的还原作用部分与1-Cys Prx的氧化形式是稳定的亚磺酸（Cys-SOH）而非二硫键这一事实有关。此外，活性位点中的一个组氨酸残基是必需的。事实上，我们设计了具有这两个特征的2-Cys Prx，它表现出抗坏血酸过氧化物酶活性。这些数据代表了硫醇特异性抗氧化范式的一个突破。抗坏血酸可能是长期以来人们一直在寻找的1-Cys Prx的生物还原剂。由于细胞中抗坏血酸含量很高，抗坏血酸/蛋白质亚磺酸对代表了体内尚未探索的氧化还原生物化学的一个方面。
