Inhibition of chrysin on xanthine oxidase activity and its inhibition mechanism.
Chrysin, a bioactive flavonoid, was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid and finally causing gout. The kinetic analysis showed that chrysin possessed a strong inhibition on XO ability in a reversible competitive manner with IC50 value of (1.26±0.04)×10(-6)molL(-1). The results of fluorescence titrations indicated that chrysin bound to XO with high affinity, and the interaction was predominately driven by hydrogen bonds and van der Waals forces. Analysis of circular dichroism demonstrated that chrysin induced the conformational change of XO with increases in α-helix and β-sheet and reductions in β-turn and random coil structures. Molecular simulation revealed that chrysin interacted with the amino acid residues Leu648, Phe649, Glu802, Leu873, Ser876, Glu879, Arg880, Phe1009, Thr1010, Val1011 and Phe1013 located within the active cavity of XO. The mechanism of chrysin on XO activity may be the insertion of chrysin into the active site occupying the catalytic center of XO to avoid the entrance of xanthine and causing conformational changes in XO. Furthermore, the interaction assays indicated that chrysin and its structural analog apigenin exhibited an additive effect on inhibition of XO.
['Lin|Suyun|S|', 'Zhang|Guowen|G|', 'Liao|Yijing|Y|', 'Pan|Junhui|J|']
D047310:Apigenin D001665:Binding Sites D020134:Catalytic Domain D004789:Enzyme Activation D004791:Enzyme Inhibitors D005419:Flavonoids D007700:Kinetics D008958:Models, Molecular D011485:Protein Binding D011487:Protein Conformation D013329:Structure-Activity Relationship D013816:Thermodynamics D014969:Xanthine Oxidase
Chrysin Xanthine oxidase Inhibition mechanism Molecular simulation Competitive inhibitor Multispectroscopic methods