Structural and kinetic considerations on the catalysis of deoxyarbutin by tyrosinase

Antonio Garcia-Jimenez, Jose Antonio Teruel-Puche, Pedro Antonio Garcia-Ruiz, Adrian Saura-Sanmartin, Jose Berna, Francisco Garcia-Canovas and José Neptuno Rodriguez-Lopez

PLOS ONE, 2017, vol. 12, issue 11, 1-26

Abstract: Deoxyarbutin, a potent inhibitor of tyrosinase, could act as substrate of the enzyme. Oxytyrosinase is able to hydroxylate deoxyarbutin and finishes the catalytic cycle by oxidizing the formed o-diphenol to quinone, while the enzyme becomes deoxytyrosinase, which evolves to oxytyrosinase in the presence of oxygen. This compound is the only one described that does not release o-diphenol after the hydroxylation step. Oxytyrosinase hydroxylates the deoxyarbutin in ortho position of the phenolic hydroxyl group by means of an aromatic electrophilic substitution. As the oxygen orbitals and the copper atoms are not coplanar, but in axial/equatorial position, the concerted oxidation/reduction cannot occur and the release of a copper atom to bind again in coplanar position, enabling the oxidation/reduction or release of the o-diphenol from the active site to the medium. In the case of deoxyarbutin, the o-diphenol formed is repulsed by the water due to its hydrophobicity, and so can bind correctly and be oxidized to a quinone before being released. Deoxyarbutin has been characterized with: kcatD-Arb = 1.95 ± 0.06 s-1 and KMD-Arb = 33 ± 4 μM. Computational simulations of the interaction of β-arbutin, deoxyarbutin and their o-diphenol products with tyrosinase show how these ligands bind at the copper centre of tyrosinase. The presence of an energy barrier in the release of the o-diphenol product of deoxyarbutin, which is not present in the case of β-arbutin, together with the differences in polarity and, consequently differences in their interaction with water help understand the differences in the kinetic behaviour of both compounds. Therefore, it is proposed that the release of the o-diphenol product of deoxyarbutin from the active site might be slower than in the case of β-arbutin, contributing to its oxidation to a quinone before being released from the protein into the water phase.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0187845

DOI: 10.1371/journal.pone.0187845

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