Study on the interaction mechanism between luteoloside and xanthine oxidase by multi‐spectroscopic and molecular docking methods

Abstract

Gout is an inflammatory joint disease caused by urate crystal deposition, which is associated with hyperuricemia. Gout will take place when the uric acid accumulates. Xanthine oxidase (XO) is a crucial enzyme in the formation of uric acid. Inhibiting XO is one of the means to ameliorate gout. Luteoloside is a kind of natural flavonoid, which has an excellent prospect for relieving gout. But there are few reports on the interaction mechanism between luteoloside and XO currently. In this study, the interaction mechanism between luteoloside and XO was explored using spectroscopy and molecular docking. The fluorescence spectroscopy results indicated that luteoloside could make the intrinsic fluorescence of XO quenched, and the binding constant between luteoloside and XO was (1.85 ± 0.22) × 103 L mol−1 at 298 K. The synchronous fluorescence spectroscopy results showed that the absorption peaks of Tyr and Trp shifted blue, and the hydrophobicity of the microenvironment increased. Moreover, CD spectra showed that α‐helix of XO decreased, β‐sheet and β‐turn increased after adding luteoloside. The results of molecular docking analysis showed that XO could combine with luteoloside through hydrogen bonds and hydrophobic force. The results indicated that luteoloside could remarkably interact with XO. Insights into the interaction mechanism provide a necessary basis for the search for low‐toxic natural products as targets of XO. Highlights Luteoloside and xanthine oxidase was a strong binding mode and had only one binding site. Luteoloside could cause α‐helix reduced, β‐sheet and β‐turn increased, and change the secondary structure of XO. The binding between luteoloside and xanthine oxidase was a spontaneous process. The main binding force was hydrophobic force between luteoloside and xanthine oxidase.

A biophysical approach to study the impact of muscle relaxant drug tizanidine on stability and activity of serum albumins

“…13 The far UV-CD spectra were used to investigate the dynamics, interaction, and folding of proteins and to measure the helical content. To study the effect of TND (10,20, and 40 μM) on proteins (BSA/HSA) conformational change, the characteristic alpha-helical peaks (at 208 and 222 nm)…”

“…For getting a better perspective of protein interactions with molecules, spectroscopic and computational analyses are widely employed. Enzyme xanthine oxidase and the flavonoid luteoloside binding was studied by Chen et al, employing multi‐spectroscopic and the molecular docking method 20 . The transport proteins, serum albumins, HSA and BSA, are also explored for their interactions with drugs and other molecules.…”

“…Enzyme xanthine oxidase and the flavonoid luteoloside binding was studied by Chen et al, employing multi-spectroscopic and the molecular docking method. 20 The transport proteins, serum albumins, HSA and BSA, are also explored for their interactions with drugs and other molecules. Huang et al carried out BSA interaction studies with a glycoside kusaginin.…”

Mechanism of flavonoids inhibiting xanthine oxidase and alleviating hyperuricemia from structure–activity relationship and animal experiments: A review

“…It mainly binds to residues in the active site pocket of XO (including Glu802, Leu873, Phe914, Arg880, Phe1009, Thr1010, Val1011, Leu1014, and Pro1076) through hydrophobic interactions, thereby altering the microenvironment and secondary structure of XO and reducing its catalytic activity (Pauff & Hille, 2009;Yan et al, 2013). Chen, Luo et al (2022), Chen, Zhu et al (2022), andChen, Wang et al (2022) reported that luteoloside, a derivative of luteolin, also inhibited XO activity; the luteoloside-XO interaction was spontaneous and, like luteolin, luteoloside inhibited the activity of XO by altering the secondary structure of XO (increasing the contents of β-sheets and β-turn, and decreasing the α-helix content of XO), besides enhancing the hydrophobicity of XO by forming hydrogen bonds and hydrophobic forces. By contrast, 6-hydroxyluteolin interacts with XO by electrostatic interaction forces (π-π T-shaped bond) and hydrogen bonds and shows high affinity for the binding site of XO (Cheng et al, 2015).…”

“…Rasoulzadeh et al (2009) mainly reviewed the interaction between plant flavonoids (mixtures) and molybdenum hydroxylases (XO and aldehyde oxidase). In addition, the role of some foods with a high content of flavonoids (e.g., tea and grapes) in XO inhibition and treatment of HUA has also been reviewed (Chen, Luo, et al, 2022;Chen, Zhu, et al, 2022;Chen, Wang, et al, 2022;Dwibedi et al, 2022;Feng, Ou et al, 2022;Mehmood et al, 2019). However, to our knowledge, the mechanism by which pure flavonoids exert their anti-hyperuricemic effects by the modulation of XO activity in light of both in vitro and in vivo has not been reviewed from the structure-activity relationship and animal experiments.…”