title: Effect of hesperetin on tyrosinase: inhibition kinetics integrated computational simulation study.
abstract: Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using inhibition kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K(i)=4.03±0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: -34.41 kcal/mol and for AutoDock4.2: -5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the inhibition of tyrosinase in response to flavonoids. A combination of inhibition kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms.
authors.affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, PR China.
authors.forename: Yue-Xiu
authors.initials: YX
authors.lastname: Si
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
authors.forename: Shang-Jun
authors.initials: SJ
authors.lastname: Yin
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
mesh_terms: D000465:Algorithms; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D047309:Flavones / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry; D006569:Hesperidin / Q000737:chemistry*; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013053:Spectrophotometry / Q000379:methods
chemical_list: C515594:8-anilino-1-naphthalenesulfonic acid; D000817:Anilino Naphthalenesulfonates; D047309:Flavones; D005419:Flavonoids; D007980:Levodopa; D006569:Hesperidin; D014442:Monophenol Monooxygenase; C013015:hesperetin