The Effect of D-(−)‎-arabinose on Tyrosinase : An Integrated Study Using Computational Simulation and Inhibition Kinetics

Abstract EN

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 (α-value =6.11±0.98, Ki=0.21±0.19 M).

Measurements of intrinsic fluorescence showed that D-(−)-arabinose induced obvious tertiary changes to tyrosinase (binding constant K=1.58±0.02 M−1, binding number n=1.49±0.06).

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.