Tyrosinase inhibitors from natural plants are currently attracting great interest. In this study, vanillic acid (VA) from red globe amaranth flower was identified as an effective tyrosinase inhibitor. The 50% inhibitory concentration values of VA were 0.53 and 0.63 mg/ml for the monophenolase and diphenolase activities of tyrosinase, respectively. VA did not function as a simple copper chelator, and it did not induce detectable changes in the enzyme conformation. An investigation into the interaction between VA and tyrosinase by docking method revealed that VA was bound to residues at the entrance to the dicopper center. This suggests that VA could strongly inhibit tyrosinase activity by hampering the binding of substrates to tyrosinase. Because of the stability of the complex, VA hindered binding of monophenol substrates better than that of diphenol substrates, which resulted in different inhibitory efficacies. A study of the mechanism of tyrosinase inhibition provided new evidence to elucidate the molecular mechanism of depigmentation by red globe amaranth plant.
