HISTONE ACETYLTRANSFERASE P300/CBP-ASSOCIATED FACTOR INHIBITION BY QUERCETIN AS ANTICANCER DRUG CANDIDATE WITH IN SILICO AND IN VITRO APPROACH
Abstract
Objective: The objective of this research was to show quercetin potency to inhibit histone acetyltransferase p300/CBP-associated factor (HAT PCAF) activity. Molecular docking study was used to show inhibition model of quercetin towards HAT PCAF and the kinetic study was used to give the information about inhibition constant (Ki) of quercetin.
Methods: Molecular docking simulations between HAT and quercetin were performed using AutoDock Vina, and the results were scored based on its Gibbs free energy change (ΔG) (the most negative ΔG). The kinetic assay of HAT PCAF inhibition by quercetin used fluorometry methods to measure enzyme inhibition by quercetin.
Results: Molecular docking showed that quercetin could inhibit HAT PCAF through binding to acetyl-CoA that involved glutamine 525 (Gln525) and cysteine 574 (Cys574) on chain A, and Cys574 and Gln581 on chain B of HAT PCAF. Quercetin also binds to histone active site on HAT PCAF through aspartic acid 610 (Asp610). The kinetic study results showed that quercetin could inhibit histone acetylation based on the fluorescence intensity. Analysis by Dixon plot showed that quercetin competes with histone. Therefore, ithad competitive inhibition. Its Ki value of 9.575 µM. Kinetic study showed the same result as molecular docking study that quercetin had potency as an HAT PCAF inhibitor.
Conclusion: The result of this research showed that quercetin had the potency to inhibit HAT PCAF through competition with HAT PCAF substrates. Quercetin could interact with the HAT PCAF active site, thus, lower the HAT PCAF activity.
Keywords: Histone acetyltransferase, Quercetin, PCAF, Epigenetic drug, Docking
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References
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