College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, P. R. China.
Protein J. 2011 Apr;30(4):273-80. doi: 10.1007/s10930-011-9329-x.
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.
由于农业和医学方面的应用，需要进行酪氨酸酶抑制研究。为了探索有效的酪氨酸酶抑制剂，计算预测和通过动力学进行的酶分析相结合非常重要。我们从双孢蘑菇中预测了酪氨酸酶的 3D 结构，使用对接算法模拟了酪氨酸酶和对苯二甲酸（TPA）之间的结合，并研究了 TPA 对酪氨酸酶的可逆抑制作用。模拟是成功的（Autodock4 的结合能为-1.54，Fred2.0 为-3.19 kcal/mol），表明 TPA 与已知在活性部位与铜离子结合的组氨酸残基相互作用。TPA 以混合抑制方式抑制酪氨酸酶，K（i）=11.01±2.12 mM。本研究表明，基于羟基和取向预测酪氨酸酶抑制的策略可能有助于筛选潜在的酪氨酸酶抑制剂。
