title: The effect of validamycin A on tyrosinase: inhibition kinetics and computational simulation.
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.
authors.affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, PR China.
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Ji
authors.forename: Yue-Xiu
authors.initials: YX
authors.lastname: Si
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.forename: Shang-Jun
authors.initials: SJ
authors.lastname: Yin
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007294:Inositol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C030790:validamycin A; D007294:Inositol; D014442:Monophenol Monooxygenase