title: Novel insights into the inhibitory mechanism of kaempferol on xanthine oxidase.
abstract: Xanthine oxidase (XO), a key enzyme in purine catabolism, is widely distributed in human tissues. It can catalyze xanthine to generate uric acid and cause hyperuricemia and gout. Inhibition kinetics assay showed that kaempferol inhibited XO activity reversibly in a competitive manner. Strong fluorescence quenching and conformational changes of XO were found due to the formation of a kaempferol-XO complex, which was driven mainly by hydrophobic forces. The molecular docking further revealed that kaempferol inserted into the hydrophobic cavity of XO to interact with some amino acid residues. The main inhibition mechanism of kaempferol on XO activity may be due to the insertion of kaempferol into the active site of XO occupying the catalytic center of the enzyme to avoid the entrance of the substrate and inducing conformational changes of XO. In addition, luteolin exhibited a stronger synergistic effect with kaempferol than did morin at the lower concentration.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University , Nanchang 330047, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
authors.forename: Guowen
authors.initials: G
authors.lastname: Zhang
authors.forename: Junhui
authors.initials: J
authors.lastname: Pan
authors.forename: Deming
authors.initials: D
authors.lastname: Gong
mesh_terms: D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D044949:Kaempferols / Q000737:chemistry*; D007700:Kinetics; D047311:Luteolin / Q000737:chemistry; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D044949:Kaempferols; C006552:kaempferol; D014969:Xanthine Oxidase; D047311:Luteolin
keywords: inhibition mechanism; kaempferol; molecular simulation; spectroscopy; xanthine oxidase