title: Kinetics and computational docking studies on the inhibition of tyrosinase induced by oxymatrine.
abstract: A combination of enzymatic inhibition kinetics and computational prediction was employed to search for an effective inhibitor of tyrosinase. We found that oxymatrine significantly inhibited tyrosinase, and that this reaction was not accompanied by detectable conformational changes. Kinetic analysis showed that oxymatrine reversibly inhibited tyrosinase in a mixed-type manner. Measurements of intrinsic and ANS-binding fluorescences showed that oxymatrine did not induce any conspicuous changes in the tertiary structure. We also conducted a docking simulation between tyrosinase and oxymatrine using two docking programs, Dock6.3 and AutoDock4.2 (binding energy was -118.81 kcal/mol for Dock6 and -8.04 kcal/mol for AutoDock4). The results also suggested that oxymatrine interacts mostly with the residues of CYS83 and HIS263 in the active site of tyrosinase. This strategy of predicting tyrosinase inhibition by simulation of docking coupling with kinetics may prove useful in screening for potential tyrosinase inhibitors. Knowledge of tyrosinase inhibition can provide medical, cosmetic, and agricultural applications. Our study suggests that oxymatrine is an important agent for various applications related to pigment formation.
authors.affiliation: College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, People's Republic of China. sunliuxx@163.com
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Liu
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Sun
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Han
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D020134:Catalytic Domain; D003198:Computer Simulation; D039301:Computers, Molecular; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D011807:Quinolizines / Q000737:chemistry*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines