Open Access

An Integrated Study of Tyrosinase Inhibition by Rutin: Progress Using a Computational Simulation

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 10ns 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 Ki = 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.

Key words: Tyrosinase; Inhibition kinetics; Rutin; Hydroxyl group; Docking simulation.

This article can be cited as:
Y-X. Si, S-J. Yin, S. Oh, Z-J. Wang, S. Ye, L. Yan, J-M. Yang, Y-D. Park, J. Lee, G-Y. Qian , An Integrated Study of Tyrosinase Inhibition by Rutin: Progress Using A Computational Simulation J. Biomol Struct Dyn 29(5), 999-1012 (2012).

Yue-Xiu Si1
Shang-Jun Yin1
Sangho Oh2
Zhi-Jiang Wang1
Sen Ye1
Li Yan3
Jun-Mo Yang4
Yong-Doo Park1,3
Jinhyuk Lee2,5*
Guo-Ying Qian1*

1College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China
2Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea
3Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, P. R. China
4Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul 135-710, Korea
5Department of Bioinformatics, University of Sciences and Technology, Daejeon 305-350, Korea

*Corresponding authors:
Dr. Jinhyuk Lee
Dr. Guo-Ying Qian
Phone: 82-428798530
Fax: 82-428798519
E-mail: jinhyuk@kribb.re.kr
Phone: 86-574-88222298
Fax: 86-574-88222298
E-mail: qianguoying_wanli@hotmail.com

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