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Unsymmetrical Binding Modes of the HOPNO Inhibitor of Tyrosinase: From Model Complexes to the Enzyme
Author(s) -
Bochot Constance,
Favre Elisabeth,
Dubois Carole,
Baptiste Benoit,
Bubacco Luigi,
Carrupt PierreAlain,
Gellon Gisèle,
Hardré Renaud,
Luneau Dominique,
Moreau Yohann,
Nurisso Alessandra,
Réglier Marius,
Serratrice Guy,
Belle Catherine,
Jamet Hélène
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201202643
Subject(s) - tyrosinase , stereochemistry , chemistry , molecular mechanics , enzyme , chelation , molecular model , binding site , computational chemistry , biochemistry , molecular dynamics , organic chemistry
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 experimental and theoretical methods, we studied an unsymmetrical 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 unsymmetrical binding of HOPNO. Comparisons have been made with the binding modes obtained on similar symmetrical complexes. Finally, by using quantum mechanics/molecular mechanics (QM/MM) calculations, we studied the binding mode in tyrosinase from a bacterial source. A new unsymmetrical binding mode was obtained, which was linked to the second coordination sphere of the enzyme.