The effect of fucoidan on tyrosinase: computational molecular dynamics integrating inhibition kinetics

Abstract

Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of inhibition kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval kinetics showed that the inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (−1.89 kcal/mol) and the hexamer (−1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.

Keywords:

• fucoidan
• tyrosinase
• inhibition kinetics
• docking simulation
• molecular dynamics simulation

Acknowledgments

This study was supported by the Zhejiang Provincial Top Key Discipline of Modern Microbiology and Application. Dr Guo-Ying Qian was supported by the grant of the National Basic Research Program of China (973 Pre-research Program) (2011CB111513). Yue-Xiu Si was financially supported by the Natural Science Foundation of Ningbo City (2011A610039). Dr Jun-Mo Yang was supported by a grant of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, 01-PJ3-PG6-01GN12-0001) and a grant from Samsung Biomedical Research Institute (C-A9-220-1). Dr Jinhyuk Lee was supported by a grant from the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program. Dr Yong-Doo Park was supported by the Natural Science Foundation of Ningbo City (2011A610019).

Notes

aData were calculated as shown in Figure 4. k ₁ and k ₂ are the first-order rate constants for the fast and slow phases, respectively.

bAccording to Tams and Welinder (1996) with slight modification, transition free energy change per second, ΔΔG° = −RTlnk, where k is a time constant for the major phase of the inactivation reaction.