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Open AccessArticle

Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant

Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, National Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun 130023, China
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Int. J. Mol. Sci. 2018, 19(9), 2808; https://doi.org/10.3390/ijms19092808
Received: 23 July 2018 / Revised: 28 August 2018 / Accepted: 11 September 2018 / Published: 18 September 2018
(This article belongs to the Special Issue Molecular Dynamics Simulations)
Zearalenone hydrolase (ZHD) is the only reported α/β-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against α-ZOL, but decreased its specific activity to β-ZOL. To understand whyV153H mutation showed catalytic specificity for α-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD α-ZOL, ZHD β-ZOL, V153H α-ZOL, and V153H β-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161–Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of α-ZOL binding to V153H mutation enlarged the distance from the OAE atom in α-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the α-ZOL. Furthermore, α-ZOL could easily form a right attack angle and attack distance in the ZHD and α-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for α-ZOL and β-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD. View Full-Text
Keywords: zearalenone hydrolase; molecular dynamics simulation; protein network analysis; alanine scanning; conformational change zearalenone hydrolase; molecular dynamics simulation; protein network analysis; alanine scanning; conformational change
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MDPI and ACS Style

Liu, Y.; Wan, Y.; Zhu, J.; Yu, Z.; Tian, X.; Han, J.; Zhang, Z.; Han, W. Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant. Int. J. Mol. Sci. 2018, 19, 2808.

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