Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, China-America CRC for Environment and Health, Shandong Province, Shandong University, Jinan 250100, People's Republic of China.
Chemosphere. 2012 Jan;86(1):92-7. doi: 10.1016/j.chemosphere.2011.09.023. Epub 2011 Oct 19.
Tetracycline (TC), chlortetracycline (CTC) and oxytetracycline (OTC) are the most common members of the widely used veterinary drug tetracyclines, the residue of which in the environment can enter human body, being potentially harmful. Lysozyme is a monomeric protein widely distributed in the nature including human beings, having many physiological and pharmaceutical functions. The aim of this study was to examine the interaction of lysozyme with the three tetracyclines (TC, CTC and OTC) through spectroscopic and molecular modeling methods. The experimental results revealed that all the three tetracyclines (TCs) can interact with lysozyme with one binding site to form TCs-lysozyme complex, mainly through electrostatic forces with the affinity order: CTC>TC>OTC. The binding of TCs can cause conformational and some microenvironmental changes of lysozyme. Furthermore, molecular docking was applied to define the specific binding sites, the results of which show that all the three TCs can bind into lysozyme cleft and interact with the key active-site residues Glu 35 or Asp 52, resulting in competitive inhibition of lysozyme activity. The accurate and full basic data in the work is beneficial to clarifying the binding mechanism of TCs with lysozyme in vivo.
四环素（TC）、金霉素（CTC）和土霉素（OTC）是广泛应用于兽医领域的四环素类药物中最常见的三种成员，其在环境中的残留可能会进入人体，具有潜在的危害性。溶菌酶是一种广泛存在于自然界（包括人类）中的单体蛋白，具有多种生理和药用功能。本研究旨在通过光谱和分子建模方法研究溶菌酶与三种四环素（TC）的相互作用。实验结果表明，三种四环素（TCs）均可与溶菌酶通过一个结合位点形成 TCs-溶菌酶复合物，主要通过静电力结合，亲和力顺序为：CTC＞TC＞OTC。TCs 的结合会引起溶菌酶构象和一些微环境的变化。此外，还应用分子对接来定义特定的结合位点，结果表明，三种 TCs 均可结合到溶菌酶的活性腔内，并与关键活性位点残基 Glu35 或 Asp52 相互作用，从而竞争性抑制溶菌酶的活性。本工作中准确而完整的基础数据有助于阐明 TCs 与体内溶菌酶的结合机制。
