Xanthine oxidase (XO), which can catalyze the formation of xanthine or hypoxanthine to uric acid, is the most important target of gout. To explore the conformational changes for inhibitor binding, molecular dockings and molecular dynamics simulations were performed. Docking results indicated that three inhibitors had similar pose binding to XO. Molecular dynamics simulations showed that the binding of three inhibitors influenced the secondary structure changes in XO. After binding to the inhibitor, the peptide Phe798-Leu814 formed different degrees of unhelix, while for the peptide Glu1065-Ser1075, only a partial helix region was formed when allopurinol was bound. Through the protein structure analysis in the simulation process, we found that the distance between the active residues Arg880 and Thr1010 was reduced and the distance between Glu802 and Thr1010 was increased after the addition of inhibitors. The above simulation results showed the similarities and differences of the interaction between the three inhibitors binding to the protein. MM-PBSA calculations suggested that, among three inhibitors, allopurinol had the best binding effect with XO followed by daidzin and puerarin. This finding was consistent with previous experimental data. Our results can provide some useful clues for further gout treatment research.
Thermal stability is a limiting factor for effective application of D-psicose 3-epimerase (DPEase) enzyme. Recently, it was reported that the thermal stability of DPEase was improved by immobilizing enzymes on graphene oxide (GO) nanoparticles. However, the detailed mechanism is not known. In this study, we investigated interaction details between GO and DPEase by performing molecular dynamics (MD) simulations. The results indicated that the domain (K248 to D268) of DPEase was an important anchor for immobilizing DPEase on GO surface. Moreover, the strong interactions between DPEase and GO can prevent loop α1′-α1 and β4-α4 of DPEase from the drastic fluctuation. Since these two loops contained active site residues, the geometry of the active pocket of the enzyme remained stable at high temperature after the DPEase was immobilized by GO, which facilitated efficient catalytic activity of the enzyme. Our research provided a detailed mechanism for the interaction between GO and DPEase at the nano–biology interface.
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