Theoretical study of phenol and 2-aminophenol docking at a model of the tyrosinase active site

Abstract

DFT calculations using the B3LYP functional are reported for a model of the (oxy)tyrosinase active site including the two copper cations, six imidazoles and dioxygen (in the oxy form), plus either phenol (taken as a model of tyrosine, the enzyme's natural substrate) or 2-aminophenol, a very efficient inhibitor. The results obtained suggest that (i) both the substrate and the inhibitor have to be deprotonated to form a stable complex with the model of the “native” form of the enzyme; (ii) only phenol binds to the oxy form; (iii) the complex formed between our oxy model and 2-aminophenate is more stable than that with phenate, suggesting a competitive inhibition mechanism between the deprotonated forms of the substrate and of the inhibitor.