A novel 65-mer peptide imitates the synergism of superoxide dismutase and glutathione peroxidase.
A novel 65-mer peptide imitates the synergism of superoxide dismutase and glutathione peroxidase.
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DOI：
10.1016/j.biocel.2011.08.019
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
Fei Yan;G. Yan;Shaowu Lv;N. Shen;Y. Mu;T. Chen;Pingsheng Gong;Yawei Xu;Limin Lv;Junqiu Liu;Jia-cong Shen;G. Luo
中科院分区：
文献类型：
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作者：
Fei Yan;G. Yan;Shaowu Lv;N. Shen;Y. Mu;T. Chen;Pingsheng Gong;Yawei Xu;Limin Lv;Junqiu Liu;Jia-cong Shen;G. Luo
活性氧（ROS）参与细胞生长、分化和死亡。过量的活性氧（如O2−、H2O2和HO）在衰老和许多人类疾病中发挥作用。超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）是生物体内重要的抗氧化酶。SOD催化O2−分解为H2O2， GPx催化谷胱甘肽（GSH）还原H2O2和其他有害过氧化物。它们不仅在催化过程中起作用，而且还相互保护，从而更有效地去除ROS，保护细胞免受损伤，维持ROS的正常代谢。为了模拟SOD与GPx的协同作用，在天然酶结构模型的基础上，设计了一种65聚肽（65P），其结构域由SOD的活性中心和GPx的催化三联体组成。在半胱氨酸营养不良表达系统中表达65P，得到Se-65P。Se-65P通过加入Cu2+和Zn2+转化为Se-CuZn-65P。Se-CuZn-65P具有良好的双活性中心，具有较高的SOD和GPx活性。通过体外模型和黄嘌呤/黄嘌呤氧化酶/Fe2+诱导的线粒体损伤模型系统来评估酶模拟物的协同作用。我们预计，具有协同作用的肽酶模拟物在治疗人类疾病方面具有广阔的前景，并作为一种有效的抗氧化剂在医学上有潜在的应用。
Reactive oxygen species (ROS) are involved in cell growth, differentiation, and death. Excessive amounts of ROS (e.g., O2−, H2O2, and HO) play a role in aging as well as in many human diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are critical antioxidant enzymes in living organisms. SOD catalyzes the dismutation of O2−to H2O2, and GPx catalyzes the reduction of H2O2and other harmful peroxides by glutathione (GSH). They not only function in catalytic processes but also protect each other, resulting in more efficient removal of ROS, protection of cells against injury, and maintenance of the normal metabolism of ROS. To imitate the synergism of SOD and GPx, a 65-mer peptide (65P), containing sequences that form the domains of the active center of SOD and the catalytic triad of GPx upon the incorporation of some metals, was designed on the basis of native enzyme structural models; 65P was expressed in the cysteine auxotrophic expression system to obtain Se-65P. Se-65P was converted into Se–CuZn-65P by incorporating Cu2+and Zn2+. Se–CuZn-65P exhibited high SOD and GPx activities because it has a delicate dual-activity center. The synergism of the enzyme mimic was evaluated by using an in vitro model and a xanthine/xanthine oxidase/Fe2+-induced mitochondrial damage model system. We anticipate that the peptide enzyme mimic with synergism is promising for the treatment of human diseases and has potential applications in medicine as a potent antioxidant.