Abstract
• Baicalein entered coenzyme cavity spontaneously to form a stable complex. • Activity of ADH was inhibited by baicalein in a non-competitive mechanism. • Baicalein altered the secondary structure of ADH and induced functional variation. • Decreased ASA of amino acid residues was the reason for fluorescence quenching. • Hydrogen bonds had been attested to be the vital forces for binary complex. Baicalein is a dietary flavonoid with extensive biological activity. Alcohol dehydrogenase (ADH) is one of the pivotal enzymes for alcohol metabolism. This research intends to investigate the mechanism of inhibition of ADH by baicalein and evaluate their structure–activity relationship. Baicalein inhibited ADH activity in a non-competitive manner. The fluorescence intensity of ADH decreased because of the formation of ADH-baicalein complex. Hydrogen bonds and van der Waals forces were the main acting forces in stabilising the complex. At 298 K, the binding constant (K a ) of baicalein to ADH was 5.41 × 10 4 L·mol −1 with one binding stoichiometry, suggesting formation of binary complex. Molecular docking analysis revealed that the hydroxyl groups on the side chain of baicalein interacted with ADH through hydrogen bonds. The interaction between baicalein and Val292 (B) may partially explain the decreased activity of ADH. The effect of baicalein on the structure of ADH was confirmed by three-dimensional (3D) fluorescence spectroscopy, circular dichroism (CD) spectroscopy, fourier-transform infrared (FT-IR) spectroscopy experiments and computer simulations. Overall, this study could reveal a novel research perspective on the therapeutic effect of baicalein and its medicinal value.
Published Version
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