The effect of validamycin A on tyrosinase: inhibition kinetics and computational simulation

Int J Biol Macromol. 2013 Apr;55:15-23. doi: 10.1016/j.ijbiomac.2012.12.040. Epub 2013 Jan 4.


In this study, we investigated validamycin A as a tyrosinase inhibitor based on its structural properties. We found that the reversible inhibition of tyrosinase by validamycin A occurred in a mixed-type manner with Ki=5.893±0.038mM, as determined by integrating kinetics studies and computational simulations. Time-interval tyrosinase studies showed that the inhibition followed first-order kinetics with two phases. Fluorescence measurements of ANS binding showed that validamycin A induced changes in the tertiary protein structure of tyrosinase. To obtain further insight, computational docking and molecular dynamics were applied, and the results indicated that HIS85, HIS244, GLU256, HIS259, and ASN260 of tyrosinase interacted with validamycin A. This strategy of predicting tyrosinase inhibition based on hydroxyl group numbers might be useful in the design and screening of potential tyrosinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Inositol / analogs & derivatives
  • Inositol / chemistry
  • Inositol / pharmacology
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / chemistry*
  • Protein Binding
  • Protein Conformation / drug effects


  • Enzyme Inhibitors
  • validamycin A
  • Inositol
  • Monophenol Monooxygenase