Effect of Cd2+ on tyrosinase: Integration of inhibition kinetics with computational simulation

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Effect of Cd2+ on tyrosinase: Integration of inhibition kinetics with computational simulation
L M Yue; Jinhyuk Lee; Z R Lu; J M Yang; Z M Ye; Y D Park
Bibliographic Citation
International Journal of Biological Macromolecules, vol. 94, no. B, pp. 836-844
Publication Year
Cadmium ions (Cd2+) are a widespread and easily absorbed toxin to both humans and animals that can be spread via food, water, and air pollution. Tyrosinase (EC is a multifunctional copper-containing enzyme that is ubiquitously expressed in animals and plays a critical role in melanin production. We evaluated the toxic effects of Cd2+ on tyrosinase activity and conformation by measuring kinetics and computationally simulating the interactions. We found Cd2+ to be a slope-hyperbolic noncompetitive-inhibition reversible inhibitor of tyrosinase, with an IC50 of 2.92 ± 0.16 mM and Ki of 0.23 ± 0.02 mM. Spectrofluorimetric measurements of intrinsic and ANS-binding fluorescence showed that Cd2+ did not induce significant changes to tyrosinase overall or to its regional active site conformations. Cd2+ showed its inactivation effect not by modulating apparent structural changes to tyrosinase, but by occupying binding sites. To gain further insight into the Cd2+/tyrosinase interaction, we performed computational docking and molecular dynamics simulations. The results consistently indicated that Cd2+ can interact with several residues near the tyrosinase active site, primarily HIS85 and ASN260. Our study provides insight into the mechanism of the toxic effects Cd2+ has on tyrosinase, which could affect the normal pigmentation pathway in animals
Cd2+Molecular dynamicsTyrosinase inhibition
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Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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