Mofidi Najjar Fayezeh, Taghavi Fereshteh, Ghadari Rahim, Sheibani Nader, Moosavi-Movahedi Ali Akbar
Department of Chemistry, Shahid Beheshti University, Tehran, Iran; Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.
Arch Biochem Biophys. 2017 Sep 15;630:81-90. doi: 10.1016/j.abb.2017.06.018. Epub 2017 Jun 28.
Non-enzymatic glycation of proteins is a post-translational modification that is produced by a covalent binding between reducing sugars and amino groups of lysine and arginine residues. In this paper the effect of pathological conditions, derived from hyperglycemia on bovine liver catalase (BLC) as a model protein was considered by measuring enzyme activity, reactive oxygen species (ROS) generation, and changes in catalase conformational properties. We observed that in the presence of glucose, the catalase activity gradually decreased. ROS generation was also involved in the glycation process. Thus, decreased BLC activity was partly considered as a result of ROS generation through glycation. However, in the presence of curcumin the amount of ROS was reduced resulting in increased activity of the glycated catalase. The effect of high glucose level and the potential inhibitory effect of curcumin on aggregation and structural changes of catalase were also investigated. Molecular dynamic simulations also showed that interaction of catalase with curcumin resulted in changes in accessible surface area (ASA) and pKa, two effective parameters of glycation, in potential glycation lysine residues. Thus, the decrease in ASA and increase in pKa of important lysine residues were considered as predominant factors in decreased glycation of BLC by curcumin.
蛋白质的非酶糖基化是一种翻译后修饰，它是由还原糖与赖氨酸和精氨酸残基的氨基之间的共价结合产生的。在本文中，通过测量酶活性、活性氧（ROS）生成以及过氧化氢酶构象性质的变化，研究了高血糖引起的病理状况对作为模型蛋白的牛肝过氧化氢酶（BLC）的影响。我们观察到，在葡萄糖存在的情况下，过氧化氢酶活性逐渐降低。ROS生成也参与了糖基化过程。因此，BLC活性降低部分被认为是糖基化产生ROS的结果。然而，在姜黄素存在的情况下，ROS的量减少，导致糖基化过氧化氢酶的活性增加。还研究了高葡萄糖水平的影响以及姜黄素对过氧化氢酶聚集和结构变化的潜在抑制作用。分子动力学模拟还表明，过氧化氢酶与姜黄素的相互作用导致潜在糖基化赖氨酸残基的可及表面积（ASA）和pKa发生变化，这是糖基化的两个有效参数。因此，重要赖氨酸残基的ASA降低和pKa升高被认为是姜黄素降低BLC糖基化的主要因素。
