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

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Title
The effect of validamycin A on tyrosinase: Inhibition kinetics and computational simulation
Author(s)
Z J Wang; S Ji; Y X Si; J M Yang; G Y Qian; Jinhyuk Lee; S J Yin
Bibliographic Citation
International Journal of Biological Macromolecules, vol. 55, pp. 15-23
Publication Year
2013
Abstract
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.
Keyword
Docking simulationInhibition kineticsMolecular dynamicsTyrosinaseValidamycin A
ISSN
0141-8130
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ijbiomac.2012.12.040
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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