Limits...
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

Plots of v versus [E]. The v value indicates the change in absorbance at 492 nm per minute at PA concentrations of 0, 100, 200, and 400 mM (labels 1 to 4, resp.). The final L-DOPA concentration was 2 mM.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3102342&req=5

fig2: Plots of v versus [E]. The v value indicates the change in absorbance at 492 nm per minute at PA concentrations of 0, 100, 200, and 400 mM (labels 1 to 4, resp.). The final L-DOPA concentration was 2 mM.

Mentions: To confirm the reversibility of PA-mediated inhibition, plots of the remaining activity versus [E] were constructed (Figure 2). The results showed straight lines passing through the origin, indicating the PA-mediated reversible inhibition, as predicted in results of Figure 1.


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

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

Plots of v versus [E]. The v value indicates the change in absorbance at 492 nm per minute at PA concentrations of 0, 100, 200, and 400 mM (labels 1 to 4, resp.). The final L-DOPA concentration was 2 mM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Plots of v versus [E]. The v value indicates the change in absorbance at 492 nm per minute at PA concentrations of 0, 100, 200, and 400 mM (labels 1 to 4, resp.). The final L-DOPA concentration was 2 mM.
Mentions: To confirm the reversibility of PA-mediated inhibition, plots of the remaining activity versus [E] were constructed (Figure 2). The results showed straight lines passing through the origin, indicating the PA-mediated reversible inhibition, as predicted in results of Figure 1.

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