Molecular Docking Studies of Ortho-Substituted Phenols to Tyrosinase Helps Discern If a Molecule Can Be an Enzyme Substrate

Int J Mol Sci. 2024 Jun 23;25(13):6891. doi: 10.3390/ijms25136891.

Abstract

Phenolic compounds with a position ortho to the free phenolic hydroxyl group occupied can be tyrosinase substrates. However, ortho-substituted compounds are usually described as inhibitors. The mechanism of action of tyrosinase on monophenols is complex, and if they are ortho-substituted, it is more complicated. It can be shown that many of these molecules can become substrates of the enzyme in the presence of catalytic o-diphenol, MBTH, or in the presence of hydrogen peroxide. Docking studies can help discern whether a molecule can behave as a substrate or inhibitor of the enzyme. Specifically, phenols such as thymol, carvacrol, guaiacol, eugenol, isoeugenol, and ferulic acid are substrates of tyrosinase, and docking simulations to the active center of the enzyme predict this since the distance of the peroxide oxygen from the oxy-tyrosinase form to the ortho position of the phenolic hydroxyl is adequate for the electrophilic attack reaction that gives rise to hydroxylation occurring.

Keywords: inhibitors; ortho-substituted phenols; substrates; tyrosinase.

MeSH terms

  • Catalytic Domain
  • Molecular Docking Simulation*
  • Monophenol Monooxygenase* / antagonists & inhibitors
  • Monophenol Monooxygenase* / chemistry
  • Monophenol Monooxygenase* / metabolism
  • Phenols* / chemistry
  • Phenols* / metabolism
  • Substrate Specificity

Substances

  • Monophenol Monooxygenase
  • Phenols