CSIR-Institute of Minerals & Materials Technology, Bhubaneswar 751 013, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India.
CSIR-Institute of Minerals & Materials Technology, Bhubaneswar 751 013, India; Department of Molecular Biology, Umea University, Sweden.
Int J Biol Macromol. 2021 Mar 1;172:418-428. doi: 10.1016/j.ijbiomac.2021.01.072. Epub 2021 Jan 15.
The major antioxidant enzyme catalase is downregulated and the enzyme activity is compromised in various disease conditions such as malarial and cancer. Hence, the restoration and protection of catalase is a promising therapeutic strategy in disease management. In the present study, for the first time we have demonstrated the protective role of well-known anti-malarial drug Artemisinin (ART) on the time and temperature-induced degradation of bovine liver catalase (BLC) activity. The findings at different time intervals and at higher temperature showed the protective role of ART on BLC activity. Molecular docking studies suggested specific binding of ART on BLC through heme group interface which was further supported by cyclic voltammetry and dynamic light scattering study. The stabilization of BLC in presence of ART was mediated through forming a BLC-ART complex with reduced and shifted electrochemical peak and increased hydrodynamic diameter. ART substantially prevents the temperature-induced reduction in α-helical content with simultaneous increment in other secondary structures like antiparallel, parallel, β-turn and random coils. Nevertheless, the protective role of ART was accepted from the enhanced thermal stability and increased T value of BLC in presence of ART at higher temperatures. Our results uncover the mechanism of interaction between ART with BLC and suggest the protective role of ART towards spatiotemporal alteration of BLC by preventing the structural and molecular change in BLC. Thus, the findings advocate ART as a potential therapeutic drug for diseases associated with reduced catalase activity.
主要抗氧化酶过氧化氢酶在疟疾和癌症等各种疾病状态下下调，酶活性受损。因此，恢复和保护过氧化氢酶是疾病管理中一种有前途的治疗策略。在本研究中，我们首次证明了众所周知的抗疟药物青蒿素（ART）对牛肝过氧化氢酶（BLC）活性的时间和温度诱导降解的保护作用。在不同时间间隔和较高温度下的研究结果表明，ART 对 BLC 活性具有保护作用。分子对接研究表明，ART 通过血红素基团界面特异性结合 BLC，循环伏安法和动态光散射研究进一步证实了这一点。ART 通过形成 BLC-ART 复合物来稳定 BLC，该复合物具有还原和偏移的电化学峰以及增加的流体力学直径。ART 实质上可防止温度诱导的 α-螺旋含量减少，同时增加其他二级结构，如反平行、平行、β-转角和无规卷曲。然而，在较高温度下，ART 存在时 BLC 的热稳定性增强和 T 值增加，接受了 ART 的保护作用。我们的结果揭示了 ART 与 BLC 之间相互作用的机制，并表明 ART 通过防止 BLC 的结构和分子变化，对 BLC 的时空变化具有保护作用。因此，这些发现主张将 ART 作为与降低过氧化氢酶活性相关的疾病的潜在治疗药物。
