Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies

- Quercetin (QTN), a flavonol forms complex with Zn2+ in a mole ratio of 2:1 in terms of qtn:Zn2+.
- Activity of zinc dependent enzyme yeast alcohol dehydrogenase (ADH) is inhibited through non-competitive inhibition in presence of QTN.
- This inhibition is attributed to the conformational change of the enzyme due to complexation followed by abstraction of Zn2+ from ADH by QTN.

A multispectroscopic exploration was employed to investigate the interaction between the metallo-enzyme alcohol dehydrogenase (ADH) from yeast with bioflavonoid quercetin (QTN). Here, we have characterized the complex formation between QTN and Zn2+ in aqueous solution and then examined the effect of such complex formation on the enzymatic activity of a zinc(II)-dependent enzyme alcohol dehydrogenase from yeast. We have observed an inhibition of enzymatic activity of ADH in presence of QTN. Enzyme inhibition kinetic experiments revealed QTN as a non-competitive inhibitor of yeast ADH. Perturbation of Circular dichroic (CD) spectrum of ADH in presence of QTN is observed due to the structural changes of ADH on complexation with the above flavonoid. Our results indicate a conformational change of ADH due to removal of Zn2+ present in the enzyme by QTN. This was further established by molecular modeling study which shows that the flavonoid binds to the Zn2+ ion which maintains the tertiary structure of the metallo-enzyme. So, QTN abstracts only half of the Zn2+ ions present in the enzyme i.e. one Zn2+ ion per monomer. From the present study, the structural alteration and loss of enzymatic activity of ADH are attributed to the complex formation between QTN and Zn2+.

133