Effect of Cd2+ on tyrosinase: Integration of inhibition kinetics with computational simulation.
Int J Biol Macromol
; 94(Pt B): 836-844, 2017 Jan.
Article
en En
| MEDLINE
| ID: mdl-27629588
ABSTRACT
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 1.14.18.1) 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±0.16mM and Ki of 0.23±0.02mM. 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cadmio
/
Monofenol Monooxigenasa
/
Inhibidores Enzimáticos
/
Simulación del Acoplamiento Molecular
Límite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2017
Tipo del documento:
Article