Mutant AhpC peroxiredoxins suppress thiol-disulfide redox deficiencies and acquire deglutathionylating activity
Mutant AhpC peroxiredoxins suppress thiol-disulfide redox deficiencies and acquire deglutathionylating activity
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DOI：
10.1016/j.molcel.2007.11.029
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发表时间：
2008-01-18
期刊：
影响因子：
16
通讯作者：
Poole, Leslie B.
中科院分区：
文献类型：
--
作者：
Yamamoto, Yuii;Ritz, Dani;Poole, Leslie B.
细菌过氧化物氧还蛋白AhpC是一种半胱氨酸依赖性过氧化物酶，可以通过单个氨基酸插入转化为二硫键还原酶AhpC*，在谷胱甘肽和谷氧还蛋白途径中具有活性。在这里，我们表明，而AhpC* 是无活性的过氧化物酶，在AhpC中的其他点突变体可以在体内二硫键还原酶的活性，而不废除过氧化物酶的活性。此外，AhpC* 和几个点突变体在体外测试表现出增强的还原酶活性对谷胱甘肽和谷氧还蛋白（Grx-S-SG）之间的混合二硫化物，与这些组件的体内要求一致。值得注意的是，这种Grx-S-SG还原酶活性不依赖于过氧化物半胱氨酸，而是依赖于在过氧化物酶机制中仅起次要作用的解析半胱氨酸。此外，假定的构象变化，赋予这种不寻常的Grx-S-SG还原酶活性，是跨亚基传输。因此，AhpC和潜在的其他过氧化物酶在这个广泛的家庭可以阐述一个新的还原酶功能，消除二硫键应力。
The bacterial peroxiredoxin AhpC, a cysteine-dependent peroxidase, can be converted through a single amino acid insertion to a disulfide reductase, AhpC*, active in the glutathione and glutaredoxin pathway. Here we show that, whereas AhpC* is inactive as a peroxidase, other point mutants in AhpC can con er the in vivo disulfide reductase activity without abrogating peroxidase activity. Moreover, AhpC* and several point mutants tested in vitro exhibit an enhanced reductase activity toward mixed disulfides between glutathione and glutaredoxin (Grx-S-SG), consistent with the in vivo requirements for these components. Remarkably, this Grx-S-SG reductase activity relies not on the peroxidatic cysteine but rather on the resolving cysteine that plays only a secondary role in the peroxidase mechanism. Furthermore, putative conformational changes, which impart this unusual Grx-S-SG reductase activity, are transmissible across subunits. Thus, AhpC and potentially other peroxiredoxins in this widespread family can elaborate a new reductase function that alleviates disulfide stress.