高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (5): 971-976.doi: 10.7503/cjcu20170702

• 物理化学 • 上一篇    下一篇

头孢西丁与金属β-内酰胺酶BcⅡ相互作用的光谱分析及分子动力学模拟

史鹏辉, 边六交   

  1. 西北大学生命科学学院, 西安 710069
  • 收稿日期:2017-11-06 出版日期:2018-04-19 发布日期:2018-04-19
  • 作者简介:

    联系人简介: 边六交, 男, 博士, 教授, 博士生导师, 主要从事生物工程制药方面的研究. E-mail: bianliujiao@sohu.com

  • 基金资助:
    国家自然科学基金(批准号: 21075097)资助.

Mechanism Study on the Interaction Between Cefoxitin and Metal β-Lactamase BcⅡ Based on Spectroscopic Methods and Computional Simulations

SHI Penghui, BIAN Liujiao*   

  1. College of Life Science, Northwest University, Xi’an 710069, China
  • Received:2017-11-06 Online:2018-04-19 Published:2018-04-19
  • Contact: BIAN Liujiao
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.21075097).

摘要:

利用同步荧光光谱、 三维荧光光谱及分子动力学模拟方法研究了β-内酰胺类抗生素头孢西丁(CFX)与金属β-内酰胺酶BcⅡ之间的相互作用机制. 荧光光谱分析表明, CFX与BcⅡ在结合过程中可诱导BcⅡ构象发生改变. 分子动力学模拟结果表明, 上述构象变化是BcⅡ在CFX的诱导下通过改变其结合口袋附近Loop 构象, 使二者达到完美匹配的一个诱导契合过程, 并最终形成一个洞穴状疏水口袋以利于CFX的结合及催化水解.

关键词: 金属β-内酰胺酶;, 头孢西丁, 相互作用, 荧光光谱, 分子动力学模拟

Abstract:

The interaction mechanism between cefoxitin(CFX) and metal β-lactamase BcⅡ was studied by synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and molecular dynamics simulation. The results of fluorescence spectra show that CFX could induce the conformation changes of BcⅡ during their binding. The simulation results show that the conformational change of BcⅡ is an induction-fit process. Under the induction of CFX, the loops near the binding pocket of BcⅡ match perfectly with the substrate by changing their conformation, and eventually form a cave-like hydrophobic pocket to facilitate the binding process and catalyze hydrolysis. This study may provide some valuable reference and inspiration for the development of new antibiotics to resist the hydrolysis of metal β-lactamases.

Key words: Metal β-lactamase;, Cefoxitin, Interaction, Fluorescence spectroscopy, Molecular dynamics simulation

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