Yekta Reza, Dehghan Gholamreza, Rashtbari Samaneh, Sheibani Nader, Moosavi-Movahedi Ali Akbar
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Departments of Ophthalmology and Visual Sciences, Biomedical Engineering, and Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
J Mol Recognit. 2017 Dec;30(12). doi: 10.1002/jmr.2648. Epub 2017 Jun 19.
Pioglitazone is an important prescription antidiabetic drug with positive roles in controlling high blood sugar in patients with type 2 diabetes. In the present study, we investigated the effects of pioglitazone on the structure and function of bovine liver catalase (BLC) using different spectroscopic and theoretical methods. UV-Vis absorption, fluorescence spectroscopy, synchronous fluorescence, and circular dichroism studies revealed conformational changes in the BLC structure and heme group in the presence of different concentrations of pioglitazone. Kinetic studies indicated that pioglitazone can increase BLC activity by approximately threefold compared with free enzyme. The fluorescence quenching data showed one binding site for pioglitazone, and the binding constants at 298, 304, and 310 K were calculated as 5.01 × 10 M , 5.8 × 10 M , and 6.6 × 10 M , respectively. The static type of quenching mechanism was mainly involved in the quenching of intrinsic emission of the enzyme. Thermodynamic data suggested that hydrophobic interactions played a major role in the binding reaction of pioglitazone with BLC. The molecular docking studies indicated that pioglitazone interacts with the cavity in the middle of the β-barrel and wrapping domain of BLC. Thus, pioglitazone can increase catalase activity by changing the BLC structure.
吡格列酮是一种重要的处方抗糖尿病药物，对控制2型糖尿病患者的高血糖具有积极作用。在本研究中，我们使用不同的光谱学和理论方法研究了吡格列酮对牛肝过氧化氢酶（BLC）结构和功能的影响。紫外可见吸收光谱、荧光光谱、同步荧光光谱和圆二色光谱研究表明，在不同浓度的吡格列酮存在下，BLC的结构和血红素基团发生了构象变化。动力学研究表明，与游离酶相比，吡格列酮可使BLC活性提高约三倍。荧光猝灭数据显示吡格列酮有一个结合位点，在298、304和310 K下的结合常数分别计算为5.01×10⁴ M⁻¹、5.8×10⁴ M⁻¹和6.6×10⁴ M⁻¹。静态猝灭机制主要参与了酶内在荧光的猝灭。热力学数据表明，疏水相互作用在吡格列酮与BLC的结合反应中起主要作用。分子对接研究表明，吡格列酮与BLC的β桶中间腔和包裹结构域相互作用。因此，吡格列酮可通过改变BLC结构来提高过氧化氢酶活性。
