title: Kinetic, structural and molecular docking studies on the inhibition of tyrosinase induced by arabinose.
abstract: Tyrosinase plays a central role in biological pigment formation, and hence knowledge of tyrosinase catalytic mechanisms and regulation may have medical, cosmetic, and agricultural applications. We found in this study that arabinose significantly inhibited tyrosinase, and this was accompanied by conformational changes in enzyme structure. Kinetic analysis showed that arabinose-mediated inactivation followed first-order kinetics, and single and multiple classes of rate constants were measured. Arabinose displayed a mixed-type inhibitory mechanism with K(i)=0.22±0.07 mM. Measurements of intrinsic and ANS-binding fluorescence showed that arabinose induced tyrosinase to unfold and expose inner hydrophobic regions. We simulated the docking between tyrosinase and arabinose (binding energies were -26.28 kcal/mol for Dock6.3 and -2.02 kcal/mol for AutoDock4.2) and results suggested that arabinose interacts mostly with His61, Asn260, and Met280. The present strategy of predicting tyrosinase inhibition by simulation of docking by hydroxyl groups may prove useful in screening for potential tyrosinase inhibitors, as shown here for arabinose.
authors.affiliation: Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, PR China.
authors.forename: Wei-Jiang
authors.initials: WJ
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Zhuo Ming
authors.initials: ZM
authors.lastname: Ye
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D001089:Arabinose / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000187:drug effects
chemical_list: D000447:Aldehydes; D004791:Enzyme Inhibitors; D001089:Arabinose; D014442:Monophenol Monooxygenase