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工程化别构抗氧化硒酶的可逆 Ca(2+)开关。

Reversible Ca(2+) switch of an engineered allosteric antioxidant selenoenzyme.

机构信息

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Road, Changchun 130012 ( P.R. China).

出版信息

Angew Chem Int Ed Engl. 2014 Dec 1;53(49):13536-9. doi: 10.1002/anie.201407135. Epub 2014 Oct 6.

Abstract

A Ca(2+) -responsive artificial selenoenzyme was constructed by computational design and engineering of recoverin with the active center of glutathione peroxidase (GPx). By combining the recognition capacity for the glutathione (GSH) substrate and the steric orientation of the catalytic selenium moiety, the engineered selenium-containing recoverin exhibits high GPx activity for the catalyzed reduction of H2 O2 by glutathione (GSH). Moreover, the engineered selenoenzyme can be switched on/off by Ca(2+) -induced allosterism of the protein recoverin. This artificial selenoenzyme also displays excellent antioxidant ability when it was evaluated using a mitochondrial oxidative damage model, showing great potential for controlled catalysis in biomedical applications.

摘要

通过计算设计和工程改造具有谷胱甘肽过氧化物酶(GPx)活性中心的恢复蛋白,构建了一种对 Ca(2+) 响应的人工硒酶。通过结合对谷胱甘肽(GSH)底物的识别能力和催化硒部分的空间取向,工程化的含硒恢复蛋白表现出对谷胱甘肽(GSH)催化还原 H2 O2 的高 GPx 活性。此外,该工程化的硒酶可以通过蛋白恢复蛋白的 Ca(2+) 诱导变构来开启/关闭。当使用线粒体氧化损伤模型评估时,这种人工硒酶还显示出出色的抗氧化能力,在生物医学应用中具有控制催化的巨大潜力。

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