Effect of luteolin on xanthine oxidase: Inhibition kinetics and interaction mechanism merging with docking simulation

• Published in: Food chemistry Vol. 141; no. 4; pp. 3766 - 3773
• Main Authors: Yan, Jiakai, Zhang, Guowen, Hu, Yuting, Ma, Yadi
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 15-12-2013; Elsevier
• Subjects: Apium graveolens - chemistry; Binding Sites; Biological and medical sciences; Capsicum - chemistry; Circular dichroism; Enzyme Inhibitors - chemistry; Fluorescence quenching; Food toxicology; Humans; Inhibition kinetics; Kinetics; Luteolin; Luteolin - chemistry; Medical sciences; Molecular Docking Simulation; Molecular simulation; Plant Extracts - chemistry; Protein Binding; Toxicology; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - chemistry; Molecular simulation; Xanthine oxidase; Inhibition kinetics; Luteolin; Fluorescence quenching; Circular dichroism; Enzyme; Fluorescence; Molecular interaction; Antioxidant; Flavonoid; Micronutrient; Polyphenol; Simulation; EC 1.1.3.22; Phenols; Proanthocyanidin; Oxidoreductases; Kinetics; Inhibition; Molecular biology; Mechanism of action
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2013.06.092

•Luteolin exhibits a significant inhibitory activity on xanthine oxidase (XO).•Luteolin reversibly inhibits XO in a competitive manner.•Luteolin quenches the fluorescence of XO through a static quenching mechanism.•The binding of luteolin to XO induces changes in the secondary structure of XO.•Molecular docking reveals luteolin mainly binds to molybdopterin domain of XO.
Xanthine oxidase (XO) catalyses hypoxanthine and xanthine to uric acid in human metabolism. Overproduction of uric acid will lead to hyperuricemia and finally cause gout and other diseases. Luteolin is one of the major components of celery and green peppers, its inhibitory activity on XO and their interaction mechanism were evaluated by multispectroscopic methods, coupled with molecular simulation. It was found that luteolin reversibly inhibited XO in a competitive manner with inhibition constant (Ki) value of (2.38±0.05)×10−6moll−1. Luteolin could bind to XO at a single binding site and the binding was driven mainly by hydrophobic interactions. Analysis of synchronous fluorescence and circular dichroism spectra demonstrated that the microenvironment and secondary structure of XO were altered upon interaction with luteolin. The molecular docking results revealed luteolin actually interacted with the primary amino acid residues located within the active site pocket of XO.