The unravelling of the complex pattern of tyrosinase inhibition

Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclus...

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Detalles Bibliográficos
Autores: Deri, Batel, Kanteev, Margarita, Goldfeder, Mor, Lecina, Daniel, Guallar, Víctor|||0000-0002-4580-1114, Adir, Noam, Fishman, Ayelet
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/90867
Acceso en línea:https://hdl.handle.net/2117/90867
https://dx.doi.org/10.1038/srep34993
Access Level:acceso abierto
Palabra clave:Melanins--Biosynthesis
Tyrosinosis
Molecular models
Inhibitor
Tyrosinases
Tyrosinase inhibitors
TyrBm activity
Melanin
Inhibidors enzimàtics
Tiroxina
Àrees temàtiques de la UPC::Enginyeria biomèdica
Descripción
Sumario:Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclusive evidence of the inhibition mechanism of two well studied tyrosinase inhibitors, KA (kojic acid) and HQ (hydroquinone), which are extensively used in hyperpigmentation treatment. KA is reported in the literature with contradicting inhibition mechanisms, while HQ is described as both a tyrosinase inhibitor and a substrate. By visualization of KA and HQ in the active site of TyrBm crystals, together with molecular modeling, binding constant analysis and kinetic experiments, we have elucidated their mechanisms of inhibition, which was ambiguous for both inhibitors. We confirm that while KA acts as a mixed inhibitor, HQ can act both as a TyrBm substrate and as an inhibitor.