Mixed-type inhibition of tyrosinase from agaricus bisporus by terephthalic acid: Computational simulations and kinetics

Shang Jun Yin, Yue Xiu Si, Yong Fu Chen, Guo Ying Qian, Zhi Rong Lü, Sangho Oh, Jinhyuk Lee, Sanghyuk Lee, Jun Mo Yang, Dong Youn Lee, Yong Doo Park

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalProtein Journal
Volume30
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Docking simulation
  • Hydroxyl group
  • Inhibition kinetics
  • Terephthalic acid
  • Tyrosinase

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