Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant
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 increa...
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MDPI AG
2018-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ye Liu Youzhong Wan Jingxuan Zhu Zhengfei Yu Xiaopian Tian Jiarui Han Zuoming Zhang Weiwei Han |
| author_facet | Ye Liu Youzhong Wan Jingxuan Zhu Zhengfei Yu Xiaopian Tian Jiarui Han Zuoming Zhang Weiwei Han |
| author_sort | Ye Liu |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-4f78070ebc2a4b34b4c30937d9c9fde62022-12-22T03:33:46ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-09-01199280810.3390/ijms19092808ijms19092808Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H MutantYe Liu0Youzhong Wan1Jingxuan Zhu2Zhengfei Yu3Xiaopian Tian4Jiarui Han5Zuoming Zhang6Weiwei Han7Key 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaZearalenone 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.http://www.mdpi.com/1422-0067/19/9/2808zearalenone hydrolasemolecular dynamics simulationprotein network analysisalanine scanningconformational change |
| spellingShingle | Ye Liu Youzhong Wan Jingxuan Zhu Zhengfei Yu Xiaopian Tian Jiarui Han Zuoming Zhang Weiwei Han Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant International Journal of Molecular Sciences zearalenone hydrolase molecular dynamics simulation protein network analysis alanine scanning conformational change |
| title | Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant |
| title_full | Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant |
| title_fullStr | Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant |
| title_full_unstemmed | Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant |
| title_short | Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant |
| title_sort | theoretical study on zearalenol compounds binding with wild type zearalenone hydrolase and v153h mutant |
| topic | zearalenone hydrolase molecular dynamics simulation protein network analysis alanine scanning conformational change |
| url | http://www.mdpi.com/1422-0067/19/9/2808 |
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