Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity.

Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity.
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过氧化还原蛋白 1 (Prx1) 是一种双功能酶,具有不依赖半胱氨酸的过氧化氢酶样活性

DOI:
10.1042/bcj20160851
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发表时间:
2017-04-04
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Shao JZ
Shao JZ
中科院分区:
其他
文献类型:
--
作者:
Sun CC;Dong WR;Shao T;Li JY;Zhao J;Nie L;Xiang LX;Zhu G;Shao JZ

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过氧化物氧还蛋白(Peroxiredoxin,Prx)是一种半胱氨酸依赖的硫氧还蛋白。然而,我们出乎意料地观察到,Prx 1从绿色斑点河豚(TnPrx 1)能够减少过氧化氢的方式独立于半胱氨酸过氧化和还原剂。本研究旨在验证Prx 1的新功能,描述其生化特征,并探讨其在细胞中的抗氧化作用。我们已经证实,来自河豚鱼和人类的Prx 1确实具有过氧化氢酶(CAT)样活性,该活性不依赖于Cys残基和还原剂,但依赖于铁。我们已经确定,GVL基序是必不可少的CAT样活性的Prx 1,但不是半胱氨酸依赖的硫氧还蛋白过氧化物酶(POX)的活动,并产生突变体缺乏POX和/或CAT样活动的个人功能验证。我们发现TnPrx 1 POX和CAT样活性在H2 O2还原中具有不同的动力学特征。野生型TnPrx 1和突变体的过表达差异调节活性氧(ROS)和磷酸化的HEK-293 T细胞与H2 O2处理的细胞内水平的p38。Prx 1是一种双功能酶,作为POX和CAT,对ROS具有不同的亲和力。这项研究扩展了我们对Prx 1的了解,并为进一步研究这个抗氧化剂家族的生物学作用提供了新的机会。
Peroxiredoxin (Prx) was previously known as a Cys-dependent thioredoxin. However, we unexpectedly observed that Prx1 from the green spotted puffer fish Tetraodon nigroviridis (TnPrx1) was able to reduce H2O2 in a manner independent of Cys peroxidation and reductants. This study aimed to validate a novel function for Prx1, delineate the biochemical features and explore its antioxidant role in cells. We have confirmed that Prx1 from the puffer fish and humans truly possesses a catalase (CAT)-like activity that is independent of Cys residues and reductants, but dependent on iron. We have identified that the GVL motif was essential to the CAT-like activity of Prx1, but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and generated mutants lacking POX and/or CAT-like activities for individual functional validation. We discovered that the TnPrx1 POX and CAT-like activities possessed different kinetic features in the reduction of H2O2. The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species (ROS) and the phosphorylation of p38 in HEK-293T cells treated with H2O2. Prx1 is a dual-function enzyme by acting as POX and CAT with varied affinities towards ROS. This study extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.