title: Inhibitory effect of ammonium tetrathiotungstate on tyrosinase and its kinetic mechanism.
abstract: Tyrosinase requires two copper ions at the active site, in order to oxidize phenols to catechols. In this study, the inhibitory effect of the copper-chelating compound, ammonium tetrathiotungstate (ATTT), on the tyrosinase activity was investigated. ATTT was determined to inactivate the activity of mushroom tyrosinase, in a dose-dependent manner. The kinetic substrate reaction revealed that ATTT functions as a kinetically competitive inhibitor in vitro, and that the enzyme-ATTT complex subsequently undergoes a reversible conformational change, resulting in the inactivation of tyrosinase. In human melanin-producing cells, ATTT evidenced a more profound tyrosinase-inhibitory effect than has been seen in the previously identified tyrosinase inhibitors, including kojic acid and hydroquinone. Our results may provide useful information for the development of whitening agent.
authors.affiliation: Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Park
authors.forename: Jae-Rin
authors.initials: JR
authors.lastname: Lee
authors.forename: Hwa-Sun
authors.initials: HS
authors.lastname: Hahn
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Chang-Dae
authors.initials: CD
authors.lastname: Bae
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Bae
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Myong-Joon
authors.initials: MJ
authors.lastname: Hahn
mesh_terms: D000363:Agaricales / Q000201:enzymology; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008544:Melanocytes / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017973:Tungsten Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D017973:Tungsten Compounds; C020863:ammonium tetrathiotungstate; D003300:Copper; D014442:Monophenol Monooxygenase