title: An integrated study of tyrosinase inhibition by rutin: progress using a computational simulation.
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.
authors.affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China. qianguoying_wanli@hotmail.com
authors.forename: Yue-Xiu
authors.initials: YX
authors.lastname: Si
authors.forename: Shang-Jun
authors.initials: SJ
authors.lastname: Yin
authors.forename: Sangho
authors.initials: S
authors.lastname: Oh
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Sen
authors.initials: S
authors.lastname: Ye
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
mesh_terms: D020134:Catalytic Domain; D002478:Cells, Cultured / Q000187:drug effects; D003300:Copper / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012431:Rutin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D012431:Rutin; D003300:Copper; D014442:Monophenol Monooxygenase