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

Abstract

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.

Effective Zearalenone Degradation in Model Solutions and Infected Wheat Grain Using a Novel Heterologous Lactonohydrolase Secreted by Recombinant Penicillium canescens

“…According to our experimental data, the ZHD101 amino acid sequence of strain GRZ7 (265 aa) is slightly different from the closest homologue of ZHD101 from C. rosea. The amino acid sequence of ZHD101 from GRZ7 showed a high identity (99%) with ZHD101 from C. rosea with the putative catalytic triplet SHE motif (Ser102-His242-Glu126) [47]. It should be noted that the Ala65Val substitution found in the new ZHD101 is located in an unstructured region of the protein globule, and the presence of valine at the position 65 can lead to the stabilization of the protein globule due to the hydrophobization of the chain.…”

“…It should be noted that the Ala65Val substitution found in the new ZHD101 is located in an unstructured region of the protein globule, and the presence of valine at the position 65 can lead to the stabilization of the protein globule due to the hydrophobization of the chain. As for the Ser41Arg substitution, it is located in the α-helix, which can lead to some destabilization; however, this residue is far from the Ser102-His242-Glu126 triad, which determines the catalytic activity of ZHD101 [47] (Figure 1).…”

Computational Study on the Effect of Inactivating/Activating Mutations on the Inhibition of MEK1 by Trametinib

“…The inhibitor trametinib was downloaded from Chemspider, followed by optimization using Gaussian 09 software and B3LYP 6031G* set. [31][32][33] was employed to identify the appropriate binding modes and the conformation of trametinib to MEK1. Moreover, the grid maps with a box size of 48 Å × 48 Å × 48 Å points and grid-point spacing of 0.375 Å were used.…”

Single-Molecule Imaging and Computational Microscopy Approaches Clarify the Mechanism of the Dimerization and Membrane Interactions of Green Fluorescent Protein

“…However, many of the details regarding how conformational flexibility and structural changes affect the key interactions responsible for the formation of dimers remain elusive despite extensive studies. Molecular dynamics (MD) is one of the most appropriate and broadly-implemented methods for studying dynamic changes in protein structure and interactions, providing atomistic insights that cannot be obtained experimentally [12,13,14,15]. MD simulations may serve as a computational microscope, revealing important biomolecular mechanisms at spatial and temporal scales that are difficult to observe experimentally.…”