光谱法结合分子模拟技术研究左氧氟沙星与胃蛋白酶的相互作用机理

摘要

The binding of levofloxacin ( LEFX) with pepsin ( PEP) was investigated by spectroscop-ic and molecular docking methods under simulated physiological conditions. LEFX effectively quenched the fluorescence of PEP by a static quenching process. Based on the results of binding ca-pacity, the thermodynamic parameters were calculated and the molecular docking was studied. It is concluded that the LEFX can spontaneously bind with PEP mainly through electrostatic forces. The three-dimensional fluorescence spectra reveal that the microenvironment and conformation of PEP are demonstrably changed in the presence of LEFX. Since the binding of LEFX can affect the microenvi-ronment of the PEP activity site, LEFX causes the inhibition of PEP activity.%在模拟生理条件下，采用荧光光谱法结合分子对接技术研究了左氧氟沙星与胃蛋白酶的相互作用。不同温度下的Stern-Volmer曲线结果表明，左氧氟沙星主要以静态猝灭的方式使胃蛋白酶的荧光产生猝灭。由热力学数据确定了两者之间存在的作用力主要为静电作用力。三维荧光光谱实验结果表明，在左氧氟沙星与胃蛋白酶发生作用过程中引起了胃蛋白酶中酪氨酸和色氨酸残基构象的变化，从而导致胃蛋白酶发生了猝灭作用。为了进一步探讨左氧氟沙星与胃蛋白酶相互作用的分子机理，利用分子对接技术对两者的相互作用进行模拟。结果表明两者发生作用的区域位于胃蛋白酶的催化活性中心，左氧氟沙星的进入导致酶催化中心氨基酸残基的微环境发生改变，从而对胃蛋白酶的活性造成影响，这可能也是左氧氟沙星引起消化不良的主要原因。