The Effect of D-(−)-arabinose on Tyrosinase: An Integrated Study Using Computational Simulation and Inhibition Kinetics

Tyrosinase is a ubiquitous enzyme with diverse physiologic roles related to pigment production. Tyrosinase inhibition has been well studied for cosmetic, medicinal, and agricultural purposes. We simulated the docking of tyrosinase and D-(−)-arabinose and found a binding energy of −4.5 kcal/mol for theup-formof D-(−)-arabinose and −4.4 kcal/mol for thedown-form of D-(−)-arabinose. The results of molecular dynamics simulation suggested that D-(−)-arabinose interacts mostly with HIS85, HIS259, and HIS263, which are believed to be in the active site. Our kinetic study showed that D-(−)-arabinose is a reversible, mixed-type inhibitor of tyrosinase (α-value =6.11±0.98, Ki=0.21±0.19 M). Measurements of intrinsic fluorescence showed that D-(−)-arabinose induced obvious tertiary changes to tyrosinase (binding constant K=1.58±0.02 M−1, binding number n=1.49±0.06). This strategy of predicting tyrosinase inhibition based on specific interactions of aldehyde and hydroxyl groups with the enzyme may prove useful for screening potential tyrosinase inhibitors.

Download Full-text

Integrated study of the mechanism of tyrosinase inhibition by baicalein using kinetic, multispectroscopic and computational simulation analyses

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2018.06.055 ◽

2018 ◽

Vol 118 ◽

pp. 57-68 ◽

Cited By ~ 13

Author(s):

Nihong Guo ◽

Cailian Wang ◽

Chao Shang ◽

Xue You ◽

Liuyang Zhang ◽

...

Keyword(s):

Computational Simulation ◽

Tyrosinase Inhibition ◽

Integrated Study

Download Full-text

Inhibition Mechanism and Kinetic Model for Ozagrel on Mushroom Tyrosinase

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.236-238.2913 ◽

2011 ◽

Vol 236-238 ◽

pp. 2913-2916

Author(s):

Bai Li Shu ◽

Ya Juan Fan ◽

Qi Meng Zhang ◽

Ying Li Liu ◽

Yue Gu

Keyword(s):

Kinetic Model ◽

Mixed Type ◽

Kinetic Method ◽

Inhibition Mechanism ◽

Mushroom Tyrosinase ◽

Inhibition Kinetics ◽

Antithrombotic Drug ◽

Substrate Complex ◽

Mixed Type Inhibitor

This investigation shows that ozagrel, an antithrombotic drug, can inhibit mushroom tyrosinase well. The IC50 value was 3.45 mmol/L. Ozagrel was estimated to be a reversible mixed-type inhibitor of mushroom tyrosinase by Lineweaver-Burk plots. The inhibition kinetics has been studied by using the kinetic method of the substrate reaction described by Tsou. The constants of tyrosinase and tyrosinase-substrate complex inhibited by 1.0 mmol/L ozagrel have been determined to be 87.28 and 66.07 µmol/L, respectively.

Download Full-text

Effects of boldine on tyrosinase: Inhibition kinetics and computational simulation

Process Biochemistry ◽

10.1016/j.procbio.2012.11.001 ◽

2013 ◽

Vol 48 (1) ◽

pp. 152-161 ◽

Cited By ~ 11

Author(s):

Yue-Xiu Si ◽

Sunyoung Ji ◽

Wei Wang ◽

Nai-Yun Fang ◽

Qing-Xin Jin ◽

...

Keyword(s):

Computational Simulation ◽

Inhibition Kinetics ◽

Tyrosinase Inhibition

Download Full-text

An Integrated Study of Tyrosinase Inhibition by Rutin: Progress using a Computational Simulation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/073911012010525028 ◽

2012 ◽

Vol 29 (5) ◽

pp. 999-1012 ◽

Cited By ~ 43

Author(s):

Yue-Xiu Si ◽

Shang-Jun Yin ◽

Sangho Oh ◽

Zhi-Jiang Wang ◽

Sen Ye ◽

...

Keyword(s):

Computational Simulation ◽

Tyrosinase Inhibition ◽

Integrated Study

Download Full-text

Some properties of the NADP-specific malic enzyme from the moderate Halophile Vibrio Costicola

Canadian Journal of Microbiology ◽

10.1139/m80-008 ◽

1980 ◽

Vol 26 (1) ◽

pp. 50-57 ◽

Cited By ~ 6

Author(s):

Marcela S. Salvarrey ◽

Juan José Cazzulo

Keyword(s):

Salt Concentration ◽

Malic Enzyme ◽

Mixed Type ◽

The Other ◽

Inhibition Kinetics ◽

Moderate Halophile ◽

Maximal Activation ◽

Regulatory Properties ◽

Better Than ◽

Mixed Type Inhibitor

NADP-specific malic enzyme (EC 1.1.1.40) has been purified about 160-fold from the moderate halophile Vibrio costicola. The enzyme has a molecular weight of about 120 000. The purified enzyme was unstable in dilute solutions but could be stabilised by NaCl or glycerol. NH4Cl or KCl caused maximal activation at 0.1 M, but higher concentrations were inhibitory. NaCl did not activate and was instead a mixed-type inhibitor towards NH4Cl or KCl. The salt concentration affected the kinetic parameters of the reaction. The apparent Km for L-malate reached a minimal value at about 0.1 M salt; the value for NADP, on the other hand, increased continuously with the salt concentration. The reaction also required a divalent cation activator, Mn2+ being better than Co2+ or Mg2+. NADH was a mixed-type inhibitor towards both substrates, whereas oxaloacetate was strictly competitive towards L-malate and non-competitive towards NADP. The inhibition kinetics were sigmoidal for NADH and hyperbolic for oxaloacetate. The malic enzyme from V. costicola was similar to those of a marine Pseudomonas and Halobacterium cutirubrum in kinetic and regulatory properties but showed a response to salts intermediate between those of the latter enzymes.

Download Full-text

Effect of hesperetin on tyrosinase: Inhibition kinetics integrated computational simulation study

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2011.11.001 ◽

2012 ◽

Vol 50 (1) ◽

pp. 257-262 ◽

Cited By ~ 63

Author(s):

Yue-Xiu Si ◽

Zhi-Jiang Wang ◽

Daeui Park ◽

Hae Young Chung ◽

Su-Fang Wang ◽

...

Keyword(s):

Simulation Study ◽

Computational Simulation ◽

Inhibition Kinetics ◽

Tyrosinase Inhibition

Download Full-text

Inhibitory Effect of Phthalic Acid on Tyrosinase: The Mixed-Type Inhibition and Docking Simulations

Enzyme Research ◽

10.4061/2011/294724 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 25

Author(s):

Shang-Jun Yin ◽

Yue-Xiu Si ◽

Guo-Ying Qian

Keyword(s):

Phthalic Acid ◽

Mixed Type ◽

3D Structure ◽

Computational Prediction ◽

Inhibitory Effect ◽

Binding Energies ◽

Hydroxyl Groups ◽

Tyrosinase Inhibition ◽

Ans Binding ◽

Docking Simulations

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 Ki=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.

Download Full-text