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Inhibitory effect of phthalic Acid on tyrosinase: the mixed-type inhibition and docking simulations.

Yin SJ, Si YX, Qian GY - Enzyme Res (2011)

Bottom Line: For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics was important.Simulation was successful (binding energies for Dock6.3 = -27.22 and AutoDock4.2 = -0.97 kcal/mol), suggesting that PA interacts with LEU73 residue that is predicted commonly by both programs.The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.

View Article: PubMed Central - PubMed

Affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China.

ABSTRACT
Tyrosinase inhibition studies are needed due to the medicinal applications such as hyperpigmentation. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics was important. We predicted the 3D structure of tyrosinase, used a docking algorithm to simulate binding between tyrosinase and phthalic acid (PA), and studied the reversible inhibition of tyrosinase by PA. PA inhibited tyrosinase in a mixed-type manner with a K(i) = 65.84 ± 1.10 mM. Measurements of intrinsic and ANS-binding fluorescences showed that PA induced changes in the active site structure via indirect binding. Simulation was successful (binding energies for Dock6.3 = -27.22 and AutoDock4.2 = -0.97 kcal/mol), suggesting that PA interacts with LEU73 residue that is predicted commonly by both programs. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.

No MeSH data available.


Related in: MedlinePlus

Changes in ANS-binding fluorescence of tyrosinase at different PA concentrations. ANS (40 μM) was incubated with tyrosinase for 30 min to label the hydrophobic enzyme surfaces prior to fluorescence measurements. Data are presented as the means (n = 2).
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fig7: Changes in ANS-binding fluorescence of tyrosinase at different PA concentrations. ANS (40 μM) was incubated with tyrosinase for 30 min to label the hydrophobic enzyme surfaces prior to fluorescence measurements. Data are presented as the means (n = 2).

Mentions: To compare the intrinsic fluorescence result and further to elucidate the changes in tyrosinase hydrophobicity due to alterations of the active site shape by PA, the ANS-binding fluorescence changes were monitored in the presence of PA (Figure 7). PA gradually increased the ANS-binding fluorescence of tyrosinase in a dose-dependent manner, an indication that binding to inhibitor exposed the hydrophobic surfaces within the tyrosinase, which might be mainly caused from the active site.


Inhibitory effect of phthalic Acid on tyrosinase: the mixed-type inhibition and docking simulations.

Yin SJ, Si YX, Qian GY - Enzyme Res (2011)

Changes in ANS-binding fluorescence of tyrosinase at different PA concentrations. ANS (40 μM) was incubated with tyrosinase for 30 min to label the hydrophobic enzyme surfaces prior to fluorescence measurements. Data are presented as the means (n = 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102342&req=5

fig7: Changes in ANS-binding fluorescence of tyrosinase at different PA concentrations. ANS (40 μM) was incubated with tyrosinase for 30 min to label the hydrophobic enzyme surfaces prior to fluorescence measurements. Data are presented as the means (n = 2).
Mentions: To compare the intrinsic fluorescence result and further to elucidate the changes in tyrosinase hydrophobicity due to alterations of the active site shape by PA, the ANS-binding fluorescence changes were monitored in the presence of PA (Figure 7). PA gradually increased the ANS-binding fluorescence of tyrosinase in a dose-dependent manner, an indication that binding to inhibitor exposed the hydrophobic surfaces within the tyrosinase, which might be mainly caused from the active site.

Bottom Line: For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics was important.Simulation was successful (binding energies for Dock6.3 = -27.22 and AutoDock4.2 = -0.97 kcal/mol), suggesting that PA interacts with LEU73 residue that is predicted commonly by both programs.The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.

View Article: PubMed Central - PubMed

Affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China.

ABSTRACT
Tyrosinase inhibition studies are needed due to the medicinal applications such as hyperpigmentation. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics was important. We predicted the 3D structure of tyrosinase, used a docking algorithm to simulate binding between tyrosinase and phthalic acid (PA), and studied the reversible inhibition of tyrosinase by PA. PA inhibited tyrosinase in a mixed-type manner with a K(i) = 65.84 ± 1.10 mM. Measurements of intrinsic and ANS-binding fluorescences showed that PA induced changes in the active site structure via indirect binding. Simulation was successful (binding energies for Dock6.3 = -27.22 and AutoDock4.2 = -0.97 kcal/mol), suggesting that PA interacts with LEU73 residue that is predicted commonly by both programs. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.

No MeSH data available.


Related in: MedlinePlus