Inhibitory effect of ammonium tetrathiotungstate on tyrosinase and its kinetic mechanism.
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.
Park
Kyung-Hee
KH
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 Korea.
Lee
Jae-Rin
JR
Hahn
Hwa-Sun
HS
Kim
Young-Hoon
YH
Bae
Chang-Dae
CD
Yang
Jun-Mo
JM
Oh
Sangtaek
S
Bae
Yu-Jin
YJ
Kim
Dong-Eun
DE
Hahn
Myong-Joon
MJ
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*
D004791:Enzyme Inhibitors; D017973:Tungsten Compounds; C020863:ammonium tetrathiotungstate; D003300:Copper; D014442:Monophenol Monooxygenase