Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4
Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4
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人过氧化还原蛋白 4 过氧化物酶活性和失活的结构见解
DOI：
10.1042/bj20110380
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发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Wang, Chih-chen
中科院分区：
文献类型：
--
作者：
Wang, Xi;Wang, Likun;Wang, Chih-chen
Prx 4（peroxiredoxin 4）是唯一位于内质网（内质网）中的过氧化物酶，也是一种H2 O2的清除剂。在本研究中，我们解决了三种不同的氧化还原形式的人Prx 4的晶体结构，并表征了Prx 4与H2 O2的反应特征。Prx 4具有由五个催化二聚体构成的环形十聚体。结构分析揭示了螺旋α 2周围的构象变化和具有来自伴侣亚基的YF（Tyr-Phe）基序的C-末端区域，这是Cys（87）和Cys（208）之间的链间二硫键形成所需的，这是催化的关键步骤。对YF基序对活性位点动力学的限制作用进行了详细的结构解释。Prx 4与H2 O2具有高反应性，但易受过氧化和随后被H2 O2灭活的影响。YF基序的缺失或解离成二聚体通过增加Cys的柔性降低了Prx 4对过氧化的敏感性（87）。
Prx4 (peroxiredoxin 4) is the only peroxiredoxin located in the ER (endoplasmic reticulum) and a proposed scavenger for H2O2. In the present study, we solved crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with H2O2. Prx4 exhibits a toroid-shaped decamer constructed of five catalytic dimers. Structural analysis revealed conformational changes around helix alpha 2 and the C-terminal reigon with a YF (Tyr-Phe) motif from the partner subunit, which are required for interchain disulfide formation between Cys(87) and Cys(208), a critical step of the catalysis. The structural explanation for the restricting role of the YF motif on the active site dynamics is provided in detail. Prx4 has a high reactivity with H2O2, but is susceptible to overoxidation and consequent inactivation by H2O2. Either deletion of the YF motif or dissociation into dimers decreased the susceptibility of Prx4 to overoxidation by increasing the flexibility of Cys(87).