标题：Noncovalent Interaction of Oxytetracyciine with the Enzyme Trypsin
作者：Zhenxing Chi;Rutao Liu;Hao Zhang
作者机构：[Chi, Z] Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, 更多
通讯作者地址：[Liu, RT]Shandong Univ, Shandong Key Lab Water Pollut Control & Resource, Sch Environm Sci & Engn, China Amer CRC Environm & Hlth, 27 Shanda S Rd, Jin 更多
摘要：Oxytetracyciine (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment (e.g., animal food, soils, surface, and groundwater) is potentially harmful. In this article, the binding mode of OTC with trypsin was investigated using spectroscopic and molecular docking methods. OTC can interact with trypsin with one binding site to form OTC—trypsin complex, resulting in inhibition of trypsin activity and change of the secondary structure and the microenvironment of the tryptophan residues of trypsin. After elimination of the inner filter effect, the association constant, K, was calculated to be K_(290K) = 1.36 x 10~5 L mol~(-1), K_(298K)= 7.30 x 10~4 L mol~(-1), and K_(307K) = 3.58 x 10~4 L mol~(-1) at three different temperatures. The calculated thermodynamic parameters (negative values of ΔH° and ΔS°) indicated that van der Waals interactions and hydrogen bonds play a major role during the interaction. The molecular docking study revealed that OTC bound into the S1 binding pocket, which illustrates that the trypsin activity was competitively inhibited by OTC, in accordance with the conclusion of the trypsin activity experiment. This work establishes a new strategy to probe the toxicity of OTC and contributes to clarify its molecular mechanism of toxicity in vivo. The combination of spectroscopic and molecular docking methods in this work can be applied to investigate the potential enzyme toxicity of other small organic pollutants and drugs.