Chem. J. Chinese Universities ›› 2019, Vol. 40 ›› Issue (1): 138.doi: 10.7503/cjcu20180445

• Physical Chemistry • Previous Articles     Next Articles

Exploration of Increasing the Non-specificity Substrates Activity for the Phosphotriesterase-like Lactonase Using Molecular Dynamics Simulations

ZHU Jingxuan1, YU Zhengfei1, LIU Ye1, ZHAN Dongling2, HAN Jiarui1, TIAN Xiaopian1, HAN Weiwei1,*()   

  1. 1. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, School of Life Science, Jilin University, Changchun 130012, China
    2. College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
  • Received:2018-06-19 Online:2019-01-10 Published:2018-12-19
  • Contact: HAN Weiwei E-mail:weiweihan@jlu.edu.cn
  • Supported by:
    † Supported by the Natural Science Foundation of Jilin Province, China(Nos.20170101068JC, 20150101118JC).

Abstract:

The structural changes of phosphotriesterase-like lactonase induced by paraoxon and undecanoic-γ-lactone binding to WT SsoPox and W263F/W263T mutant were compared using molecular dynamics simulation and steered molecular dynamics simulation combined with molecular mechanics-generalized Born/surface area(MM-GB/SA) and structural interaction fingerprints(SIFt) methods. The reasons that the important residue Trp263(located in Loop 8) in SsoPox could determine the enzymatic promiscuity were listed as follow, (1) the displacements in two mutant complex could lead to a widening of the active site entrance, which allowed for tighter fitting of the substrate into the enzyme’s active site; (2) the salt bridge between Asp256 and Arg223 in the two mutant complexes occurred with a higher probability compared to two WT SsoPox complexes, which could offer a potential pathway for proton relay after catalysis. The results of comparing conformational stabilities and binding free energies between WT SsoPox and W263F/W263T mutant indicated that the complex of SsoPox and lactone was more stable and had lower binding free energy during the simulation, which was beneficial to the recognition of the substrate and nucleophilic attack of the hydroxide on the electrophilic center of the substrate. Therefore, the stable interaction of substrate with enzyme may be a reason for the natural lactonase activity of SsoPox.

Key words: Phosphotriesterase-like lactonase, Molecular dynamics simulation, Steered molecular dynamics simulation, Molecular mechanics-generalized Born/surface area(MM-GB/SA), Structural interaction fingerprint

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