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).
1College of Biological and
Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China