Mixed-type inhibition of tyrosinase from Agaricus bisporus by terephthalic acid: computational simulations and kinetics

Protein J. 2011 Apr;30(4):273-80. doi: 10.1007/s10930-011-9329-x.


Tyrosinase inhibition studies are needed due to the agricultural and medicinal applications. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics were important. We predicted the 3D structure of tyrosinase from Agaricus bisporus, used a docking algorithm to simulate binding between tyrosinase and terephthalic acid (TPA) and studied the reversible inhibition of tyrosinase by TPA. Simulation was successful (binding energies for Autodock4 = -1.54 and Fred2.0 = -3.19 kcal/mol), suggesting that TPA interacts with histidine residues that are known to bind with copper ions at the active site. TPA inhibited tyrosinase in a mixed-type manner with a K ( i ) = 11.01 ± 2.12 mM. Measurements of intrinsic and ANS-binding fluorescences showed that TPA induced no changes in tertiary structure. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricus / chemistry
  • Agaricus / enzymology*
  • Amino Acid Sequence
  • Computer Simulation
  • Free Radical Scavengers / pharmacology*
  • Models, Molecular
  • Molecular Sequence Data
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / metabolism*
  • Phthalic Acids / pharmacology*
  • Protein Binding
  • Protein Conformation


  • Free Radical Scavengers
  • Phthalic Acids
  • terephthalic acid
  • Monophenol Monooxygenase