26 research outputs found
Thermodynamic, kinetic and docking studies of some unsaturated fatty acids-quercetin derivatives as inhibitors of mushroom tyrosinase
Inhibition of activity and stability structure of mushroom tyrosinase (MT) is highly
important, since it is a key enzyme of melanogenesis playing various roles in organisms. In this study,
thermodynamic stability and diphenolase activities were investigated in the presence of
quercetin-7-linoleate (ligand I) and quercetin-7-oleate (ligand II) on mushroom tyrosinase by
experimental and computational methods. Kinetic analyses showed that the inhibition mechanism of
these ligands is reversible and competitive manner. The inhibition constants values (KiI = 0.31 and KiII
= 0.43 mM) and the half maximal inhibitory concentration (IC50 = 0.58 and 0.71 mM) were
determined for ligand I and ligand II respectively. Thermal denaturation for the sole and modified
enzyme were performed by using fluorescence spectroscopy to obtain the thermodynamic parameters
of denaturation. Type of interactions and orientation of ligands were determined by molecular docking
simulations. The binding affinities of the MT–ligand complexes during docking were calculated. In the
computational studies performed using the MT (PDBID: 2Y9X) from which tropolone was removed,
we showed that the ligands occupied different pockets in MT other than the active site. The best
binding energies with values of −9 and −7.9 kcal/mol were calculated and the MolDock scores of the
best poses with the lowest root mean square deviation (RMSD) were obtained as −172.70 and −165.75
kcal/mol for complexes of MT–ligand I and MT–ligand II, respectively. Computational simulations and
experimental analysis demonstrated that the ligands increased the mushroom tyrosinase stability by
reducing the activity of enzyme. In this regard, ligand I showed the potent inhibitory and played an
important role in enzyme stabilit
A Comparative Interaction between Copper Ions with Alzheimer's β
The interaction of Cu2+ with the first 16 residues of the Alzheimer's amyliod β peptide, Aβ(1–16), and human serum albumin (HSA) were studied in vitro by isothermal titration calorimetry at pH 7.2 and 310 K in aqueous solution. The solvation parameters recovered from the extended solvation model indicate that HSA is involved in the transport of copper ion. Complexes between Aβ(1–16) and copper ions have been proposed to be an aberrant interaction in the development of Alzheimer's disease, where Cu2+ is involved in Aβ(1–16) aggregation. The indexes of stability indicate that HSA removed Cu2+ from Aβ(1–16), rapidly, decreased Cu-induced aggregation of Aβ(1–16), and reduced the toxicity of Aβ(1–16) + Cu2+ significantly