Unsymmetrical Binding Modes of the HOPNO Inhibitor of Tyrosinase: From Model Complexes to the Enzyme.

The deciphering of the binding mode of tyrosinase (Ty) inhibitors is essential to understand how to regulate the tyrosinase activity. In this paper, by combining exptl. and theor. methods, we studied an unsym. tyrosinase functional model and its interaction with 2-hydroxypyridine-N-oxide (HOPNO), a new and efficient competitive inhibitor for bacterial Ty. The tyrosinase model was a dinuclear copper complex bridged by a chelated ring with two different complexing arms (namely (bis(2-ethylpyridyl)amino)methyl and (bis(2-methylpyridyl)amino)methyl). The geometrical asymmetry of the complex induces an unsym. binding of HOPNO. Comparisons have been made with the binding modes obtained on similar sym. complexes. Finally, by using quantum mechanics/mol. mechanics (QM/MM) calcns., we studied the binding mode in tyrosinase from a bacterial source. A new unsym. binding mode was obtained, which was linked to the second coordination sphere of the enzyme. [on SciFinder(R)]

Références

Titre
Unsymmetrical Binding Modes of the HOPNO Inhibitor of Tyrosinase: From Model Complexes to the Enzyme.
Type de publication
Article de revue
Année de publication
2013
Revue
Chem. - A Eur. J.
Volume
19
Pagination
3655–3664
ISSN
0947-6539
Soumis le 12 avril 2018