Tyrosinase is a ubiquitous enzyme with diverse physiologic roles related to pigment production. Tyrosinase inhibition has been well studied for cosmetic, medicinal, and agricultural purposes. We simulated the docking of tyrosinase and D-(？)-arabinose and found a binding energy of ？4.5？kcal/mol for theup-formof D-(？)-arabinose and ？4.4？kcal/mol for thedown-form of D-(？)-arabinose. The results of molecular dynamics simulation suggested that D-(？)-arabinose interacts mostly with HIS85, HIS259, and HIS263, which are believed to be in the active site. Our kinetic study showed that D-(？)-arabinose is a reversible, mixed-type inhibitor of tyrosinase ( -value？ , ？M). Measurements of intrinsic fluorescence showed that D-(？)-arabinose induced obvious tertiary changes to tyrosinase (binding constant ？M？1, binding number ). This strategy of predicting tyrosinase inhibition based on specific interactions of aldehyde and hydroxyl groups with the enzyme may prove useful for screening potential tyrosinase inhibitors. 1. Introduction Tyrosinase (EC 1.14.18.1) is a ubiquitous enzyme with diverse physiologic roles related to pigment production. It plays a central role in melanin synthesis in skin [1, 2], the browning of vegetables [3, 4], wound healing [5], and cuticle formation in insects [6, 7]. Structurally, tyrosinase belongs to the type 3 copper protein family [8, 9], which consists of two copper ions individually coordinated with three histidine residues at the active site. Tyrosinases are directly involved in several reactions and carry out catalytic steps such as the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA), the oxidation of DOPA to DOPA quinone, and the oxidation of 5,6-dihydroxyindole to 5,6-dihydroxuquinone [10, 11]. In addition to its catalytic features, tyrosinase is distinctive from other enzymes because it displays various inhibition patterns. Tyrosinase inhibition has been extensively studied for cosmetic, medicinal, and agricultural purposes [12]. The tyrosinase mechanism is complex, and this enzyme can catalyze multiple reactions. Despite several reported crystallographic structures of tyrosinase, the 3D structure and architecture of the active site are not well understood [22, 23]. Mechanistic studies must involve a variety of computational methods and kinetic analysis to derive the structure-function relationship between substrates and ligands. The inhibitory effect of compounds with sugar backbones on tyrosinase are of great interest [20, 24, 25]. D-(–)-arabinose, a potential tyrosinase inhibitor, is an aldopentose with one
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