a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
J Biomol Struct Dyn. 2018 Feb;36(2):387-397. doi: 10.1080/07391102.2017.1278721. Epub 2017 Jan 19.
Linezolid, one of the reserve antibiotic of oxazolidinone class has wide range of antimicrobial activity. Here we have conducted a fundamental study concerning the dynamics of its interaction with bovine serum albumin (BSA), and the post binding modification of the later by employing different spectroscopic (absorption, fluorescence and circular dichroism (CD) spectroscopy) and molecular docking tools. Gradual quenching of the tryptophan (Trp) fluorescence upon addition of linezolid to BSA confirms their interaction. Analysis of fluorescence quenching at different temperature indicates that the interaction is made by static complex formation and the BSA has one binding site for the drug. The negative Gibbs energy change (ΔG), and positive values of enthalpy change (ΔH) and entropy change (ΔS) strongly suggest that it is an entropy driven spontaneous and endothermic reaction. The reaction involves hydrophobic pocket of the protein, which is further stabilized by hydrogen bonding and electrostatic interactions as evidenced from 8-anilino-1-napthalene sulfonic acid, sucrose and NaCl binding studies. These findings also support the molecular docking study using AutoDock 4.2. The influence of this interaction on the secondary structure of the protein is negligible as evidenced by CD spectroscopy. So, from these findings, we conclude that linezolid interacts with BSA in 1:1 ratio through hydrophobic, hydrogen bonding and ionic interactions, and this may not affect the secondary structure of the protein.
利奈唑胺是噁唑烷酮类的储备抗生素之一，具有广泛的抗菌活性。在这里，我们进行了一项基础研究，涉及它与牛血清白蛋白（BSA）相互作用的动力学，以及通过使用不同的光谱（吸收，荧光和圆二色性（CD）光谱）和分子对接工具对后者进行的结合后修饰。向 BSA 中添加利奈唑胺会逐渐猝灭色氨酸（Trp）荧光，从而证实它们之间的相互作用。在不同温度下分析荧光猝灭表明，该相互作用是通过静态复合物形成进行的，BSA 有一个药物结合位点。负的吉布斯自由能变化（ΔG），正的焓变（ΔH）和熵变（ΔS）值强烈表明，这是一个熵驱动的自发和吸热反应。该反应涉及蛋白质的疏水口袋，如 8-苯胺-1-萘磺酸、蔗糖和 NaCl 结合研究所示，氢键和静电相互作用进一步稳定了该反应。这些发现也支持使用 AutoDock 4.2 的分子对接研究。如 CD 光谱所示，这种相互作用对蛋白质二级结构的影响可以忽略不计。因此，根据这些发现，我们得出结论，利奈唑胺以 1:1 的比例通过疏水、氢键和离子相互作用与 BSA 相互作用，这可能不会影响蛋白质的二级结构。
