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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

Computational docking simulation of binding between tyrosinase and PA. The modeled 3D structure of tyrosinase using SWISS-MODEL to assemble 556 amino acids selected with a homology-modeling protocol. Two copper ions (balls) coordinated with six histidines, as indicated the blue colors in the figure. The pink stick is PA as docked by Dock6.3. The green stick is PA as docked by AutoDock4.2.
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fig8: Computational docking simulation of binding between tyrosinase and PA. The modeled 3D structure of tyrosinase using SWISS-MODEL to assemble 556 amino acids selected with a homology-modeling protocol. Two copper ions (balls) coordinated with six histidines, as indicated the blue colors in the figure. The pink stick is PA as docked by Dock6.3. The green stick is PA as docked by AutoDock4.2.

Mentions: Because the crystallographic structure of tyrosinase is not available, we selected a template structure from the PDB (2zmxA) to simulate the 3D structure of tyrosinase. In the predicted structure of tyrosinase, a binding pocket is indicated with two coppers: one is coordinated to HIS38, HIS54, and HIS63, and the other is coordinated to HIS190, HIS194, and HIS216, respectively (Figure 8). The docking simulation of binding between PA and tyrosinase was successful in producing a significant score (binding energy for Dock6.3 was −27.22 kcal/mol). We searched for PA-binding residues within tyrosinase that were close to each other and found the most important residues at THR62, GLU67, LEU73, and ASP240 predicted from Dock6.3. In the same way, AutoDock4.2 was also applied to probe docking sites. As a result, PA-binding residues were predicted as GLU67 and LEU73 with a relatively low score (binding energy for AutoDock4.2 was −0.97 kcal/mol). We found that LEU73 has been commonly predicted from both programs. The docking simulations provided informative data for the PA as a tyrosinase inhibitor by identifying binding residues near to active site pocket, which might directly affect the L-DOPA substrate docking and catalysis by inducing regional structure changes.


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

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

Computational docking simulation of binding between tyrosinase and PA. The modeled 3D structure of tyrosinase using SWISS-MODEL to assemble 556 amino acids selected with a homology-modeling protocol. Two copper ions (balls) coordinated with six histidines, as indicated the blue colors in the figure. The pink stick is PA as docked by Dock6.3. The green stick is PA as docked by AutoDock4.2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Computational docking simulation of binding between tyrosinase and PA. The modeled 3D structure of tyrosinase using SWISS-MODEL to assemble 556 amino acids selected with a homology-modeling protocol. Two copper ions (balls) coordinated with six histidines, as indicated the blue colors in the figure. The pink stick is PA as docked by Dock6.3. The green stick is PA as docked by AutoDock4.2.
Mentions: Because the crystallographic structure of tyrosinase is not available, we selected a template structure from the PDB (2zmxA) to simulate the 3D structure of tyrosinase. In the predicted structure of tyrosinase, a binding pocket is indicated with two coppers: one is coordinated to HIS38, HIS54, and HIS63, and the other is coordinated to HIS190, HIS194, and HIS216, respectively (Figure 8). The docking simulation of binding between PA and tyrosinase was successful in producing a significant score (binding energy for Dock6.3 was −27.22 kcal/mol). We searched for PA-binding residues within tyrosinase that were close to each other and found the most important residues at THR62, GLU67, LEU73, and ASP240 predicted from Dock6.3. In the same way, AutoDock4.2 was also applied to probe docking sites. As a result, PA-binding residues were predicted as GLU67 and LEU73 with a relatively low score (binding energy for AutoDock4.2 was −0.97 kcal/mol). We found that LEU73 has been commonly predicted from both programs. The docking simulations provided informative data for the PA as a tyrosinase inhibitor by identifying binding residues near to active site pocket, which might directly affect the L-DOPA substrate docking and catalysis by inducing regional structure changes.

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