Inhibition kinetics of mushroom tyrosinase by copper-chelating ammonium tetrathiomolybdate

Park, Kyung-Hee; Park, Yong‐Doo; Lee, Jae-Rin; Hahn, Hwa-Sun; Lee, Sang-Jin; Bae, Chong Woo; Yang, Jun‐Mo; Kim, Dong-Eun; Hahn, Myong‐Joon

doi:10.1016/j.bbagen.2005.06.010

Cited by 19 publications

(14 citation statements)

References 18 publications

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“…The partial conformational changes induced by TFE are likely to have affected the substrate-enzyme state of the parabolic V max changes and, simultaneously, interfered with L-DOPA docking to the active site, resulting in K m changes. Complex types of inhibition of tyrosinase by various compounds have been observed previously [25,26,[33][34][35]. Compared to these results, however, the TFE-induced mechanism of inhibition was different in two major ways: TFE did not bind directly to the copper ions of the active site, and secondary structural changes were accompanied by tertiary structural changes that directly induced a complete loss of activity.…”

Section: Discussioncontrasting

confidence: 53%

The Effect of Trifluoroethanol on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Simulations

Shi

Wang

et al. 2009

Appl Biochem Biotechnol

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We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of tyrosinase. TFE increased the degree of secondary structure of tyrosinase, which directly resulted in enzyme inactivation. A reciprocal study showed that TFE inhibited tyrosinase in a slope-parabolic mixed-type inhibition manner (K (I) = 0.5 +/- 0.096 M). Time-interval kinetic studies showed that the inhibition was best described as first order with biphasic processes. Intrinsic and 1-anilinonaphthalene-8-sulfonate-binding fluorescences were also measured to gain more insight into the supposed structural changes; these showed that TFE induced a conspicuous tertiary structural change in tyrosinase by exposing hydrophobic surfaces. We also predicted the tertiary structure of tyrosinase and simulated its docking with TFE. The docking simulation was successful with significant scores (binding energy for Autodock4 = -4.75 kcal/mol; for Dock6 = -23.07 kcal/mol) and suggested that the TRP173 residue was mainly responsible for the interaction with TFE. Our results provide insight into the structure of tyrosinase and allow us to describe a new inhibition strategy that works by inducing conformational changes rather than targeting the active site of the protein.

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Section: Discussioncontrasting

confidence: 53%

The Effect of Trifluoroethanol on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Simulations

Shi

Wang

et al. 2009

Appl Biochem Biotechnol

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“…23) As a result of this finding, in this study we tested another compound, ATTT, for its potential effects as an enzyme inhibitor, in which the tungstate ion is coordinated with sulfur rather than molybdate.…”

Section: Resultsmentioning

confidence: 99%

“…21,22) We have, in previous studies, applied several copper-specific chelating agents to mushroom tyrosinase, in an effort to screen an effective inhibitor, with the strategy of copper chelation at the active enzyme site. 23) Among these compound, ammonium tetrathiomolybdate (ATTM) has been shown to exert a significant inhibitory effect, as compared to the effect of other tested substances. In this study, we have attempted to characterize the effects of ammonium tetrathiotungstate (ATTT) on tyrosinase.…”

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confidence: 99%

Inhibitory Effect of Ammonium Tetrathiotungstate on Tyrosinase and Its Kinetic Mechanism

et al. 2006

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Tyrosinase (monophenol, o-diphenol : oxygen oxidoreductase, EC 1.14.18.1) is a binuclear copper enzyme, which is fairly ubiquitously distributed throughout organisms, and is known to play an important role in melanin synthesis. [1][2][3][4] Tyrosinase has been demonstrated to catalyze the hydroxylation of phenols to catechols, as well as the oxidation of catechols to quinones. The active site of tyrosinase consists of two copper ions, each coordinated by histidine residues within the active sites. These two coppers are known to be essential for the catalytic activities of this enzyme.5) The binuclear copper active sites exist in all tyrosinases, regardless of source. 6,7) Therefore, the chelation of copper ions in this enzyme by flavonoid compounds or any other agents has been targeted as a strategy for the attenuation of tyrosinase activity, an objective relevant to cosmetic concerns, darkening problems in agricultural products, and certain medicinal reasons. [8][9][10][11][12][13][14] Melanin pigments are synthesized by melanocytes, and are deposited throughout the epidermis. This process determines skin color. [15][16][17][18] Tyrosinase is involved in two different ratelimiting steps in melanin synthesis; namely, the hydroxylation of tyrosine to 3,4-dihyroxyphenylalanine (DOPA), and the oxidation of DOPA to dopaquinone.19) The abnormal accumulation of melanin pigment can induce hyperpigmentations, such as freckles, melasma, and senile lentigines. These symptoms have responded, in the past, to treatment with depigmenting agents, including hydroquinone, ascorbic acid derivatives, retinoids, arbutin, and kojic acid. In particular, kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is a copper-chelator, which has been used as a cosmetic agent in skin-whitening formulations. 20) However, safer and more effective depigmenting agents are clearly needed, as kojic acid is not only carcinogenic, but its associated whitening effects are also somewhat weak. 21,22) We have, in previous studies, applied several copper-specific chelating agents to mushroom tyrosinase, in an effort to screen an effective inhibitor, with the strategy of copper chelation at the active enzyme site.23) Among these compound, ammonium tetrathiomolybdate (ATTM) has been shown to exert a significant inhibitory effect, as compared to the effect of other tested substances. In this study, we have attempted to characterize the effects of ammonium tetrathiotungstate (ATTT) on tyrosinase. ATTT has been identified as an effective decoppering reagent for copper storage-related diseases in both rats and sheep. 24,25) However, the kinetics of its inhibition in copper-containing enzymes has been the subject of only minimal exploration. Thus, we have attempted to evaluate the inhibition kinetics of tyrosinase by ATTT. Our kinetic studies revealed that ATTT was capable of the inactivation of tyrosinase in vitro. We have also verified the inhibitory effects of ATTT on tyrosinase in human melanocyte cells, as compared with those evidenced by other known inhibi...

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“…The biosynthetic pathway for melanin formation includes two steps: the hydroxylation of monophenol to o-diphenol and the oxidation of diphenol to o-quinones [1][2][3][4]. Furthermore, in some vegetables and fruits, tyrosinase is responsible for enzymatic browning, and it also plays a vital role in vegetables and fruits processing [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Tyrosinase (EC 1.14.18.1), a copper-containing multifunctional oxidase, is known to be a key enzyme for biosynthesis in fungi, plants and animals [1][2][3][4]. The biosynthetic pathway for melanin formation includes two steps: the hydroxylation of monophenol to o-diphenol and the oxidation of diphenol to o-quinones [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of naphthols on the activity of mushroom tyrosinase

Lin

Jia

et al. 2012

International Journal of Biological Macromolecules

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Inhibition kinetics of mushroom tyrosinase by copper-chelating ammonium tetrathiomolybdate

Cited by 19 publications

References 18 publications

The Effect of Trifluoroethanol on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Simulations

The Effect of Trifluoroethanol on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Simulations

Inhibitory Effect of Ammonium Tetrathiotungstate on Tyrosinase and Its Kinetic Mechanism

Inhibitory effects of naphthols on the activity of mushroom tyrosinase

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