Abstract

Li Yan , Shang-Jun Yin , Daeui Park , Yue-Xiu Si , Zhi-Jiang Wang , Hae Young Chung , Jun-Mo Yang , *Guo-Ying Qian , *Yong-Doo Park ,

Tyrosinase inhibition studies are important for agricultural and medicinal applications. Computational predictions and enzymatic assays via kinetics may be used to detect effective inhibitors of tyrosinase. We predicted the 3D structure of tyrosinase from Agaricus bisporus, used a docking algorithm to simulate binding between tyrosinase and oxalic acid (OA), and studied the reversible inhibition of tyrosinase by OA. Simulations were successful (binding energies for Dock6.3 = -18.76 and AutoDock4.2 = -2.47 kcal/mol), suggesting that OA interacts with the LYS224 residue that is predicted by both programs. OA inhibited tyrosinase in a mixed-type manner with a Ki = 3.16 ± 1.8 mM and IC50 = 8.0 ± 0.5 mM. Measurements of intrinsic and ANS-binding fluorescences showed that OA induced changes in the active site structure. Our results suggest that the strategy of predicting tyrosinase inhibition based on carboxyl groups and orientation may prove useful for the screening of potential tyrosinase inhibitors.