title: Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies.
abstract: 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+.
authors.affiliation: Department of Chemistry, Jadavpur University, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. Electronic address: s.bhuiya12@gmail.com.
authors.forename: Sutanwi
authors.initials: S
authors.lastname: Bhuiya
authors.affiliation: Department of Chemistry, Jadavpur University, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. Electronic address: lucy.haque@gmail.com.
authors.forename: Lucy
authors.initials: L
authors.lastname: Haque
authors.affiliation: Department of Chemistry, Jadavpur University, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. Electronic address: ankurpradhan727@gmail.com.
authors.forename: Ankur Bikash
authors.initials: AB
authors.lastname: Pradhan
authors.affiliation: Department of Chemistry, Jadavpur University, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. Electronic address: sumandas10@yahoo.com.
authors.forename: Suman
authors.initials: S
authors.lastname: Das
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013057:Spectrum Analysis; D015032:Zinc / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011794:Quercetin; D000426:Alcohol Dehydrogenase; D015032:Zinc
keywords: Alcohol dehydrogenase (ADH); Quercetin-Zn(2+) complexation; Structural alteration and enzyme inhibition