An integrated study of tyrosinase inhibition by rutin: progress using a computational simulation |
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Authors: | Si Yue-Xiu Yin Shang-Jun Oh Sangho Wang Zhi-Jiang Ye Sen Yan Li Yang Jun-Mo Park Yong-Doo Lee Jinhyuk Qian Guo-Ying |
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Institution: | College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China. qianguoying_wanli@hotmail.com |
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Abstract: | Tyrosinase inhibition studies have recently gained the attention of researchers due to their potential application values. We simulated docking (binding energies for AutoDock Vina: -9.1 kcal/mol) and performed a molecular dynamics simulation to verify docking results between tyrosinase and rutin. The docking results suggest that rutin mostly interacts with histidine residues located in the active site. A 10 ns molecular dynamics simulation showed that one copper ion at the tyrosinase active site was responsible for the interaction with rutin. Kinetic analyses showed that rutin-mediated inactivation followed a first-order reaction and mono- and biphasic rate constants occurred with rutin. The inhibition was a typical competitive type with K(i) = 1.10±0.25 mM. Measurements of intrinsic and ANS-binding fluorescences showed that rutin showed a relatively strong binding affinity for tyrosinase and one possible binding site that could be a copper was detected accompanying with a hydrophobic exposure of tyrosinase. Cell viability testing with rutin in HaCaT keratinocytes showed that no toxic effects were produced. Taken together, rutin has the potential to be a potent anti-pigment agent. The strategy of predicting tyrosinase inhibition based on hydroxyl group number and computational simulation may prove useful for the screening of potential tyrosinase inhibitors. |
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