Deri, BatelKanteev, MargaritaGoldfeder, MorLecina, DanielGuallar i Tasies, VíctorAdir, NoamFishman, Ayelet2017-01-272017-01-272016Deri B, Kanteev M, Goldfeder M, Lecina D, Guallar i Tasies V, Adir N, Fishman A. The unravelling of the complex pattern of tyrosinase inhibition. Scientific Reports. 2016; 6: 34993. DOI: 10.1038/srep349932045-2322http://hdl.handle.net/10230/28005Tyrosinases 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.application/pdfeng© Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/srep34993Enzyme mechanismsX-ray crystallographyinfo:eu-repo/semantics/openAccess