The Effect of D-(-)-arabinose on Tyrosinase: An Integrated Study Using Computational Simulation and Inhibition Kinetics.
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, K(i) = 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.
Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China.
Hong-Jian
HJ
Liu
Sunyoung
S
Ji
Yong-Qiang
YQ
Fan
Li
L
Yan
Jun-Mo
JM
Yang
Hai-Meng
HM
Zhou
Jinhyuk
J
Lee
Yu-Long
YL
Wang