Effect of hydroxysafflor yellow A on tyrosinase: Integration of inhibition kinetics with computational simulation

•The hydroxysafflor yellow A (HSYA) binding mechanisms to tyrosinase.•HSYA is a potent whitening agent via inhibition of tyrosinase.•Computational molecular dynamics simulations between tyrosinase and HSYA.•The HSYA-mediated structural change of tyrosinase synchronized with the loss of catalytic function.

Hydroxysafflor yellow A (HSYA) is found in the flower of Carthamus tinctorius. We evaluated the effects of hydroxysafflor yellow A (HSYA) on tyrosinase kinetics and computationally simulated the interaction between HSYA and tyrosinase. HSYA was found to be a mixed-type, reversible inhibitor of tyrosinase, with a Ki of 0.285 ± 0.040 mM. Kinetic measurements of intrinsic and ANS-binding fluorescence showed that HSYA induced changes in the tertiary structure of tyrosinase. HSYA showed a relatively strong binding affinity for tyrosinase and one possible binding site was identified. To gain further insight into the HSYA/tyrosinase interaction, we performed computational docking and molecular dynamics simulations. These experiments indicated that HSYA can interact with several residues near the tyrosinase active site. Our study provides insight into the mechanism by which chalcone compounds such as flavonoids inhibit tyrosinase. Since HSYA inhibits tyrosinase and is also an antioxidant, HSYA is a potential natural antipigmentation agent.

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