Studies on the interaction mechanism between xanthine oxidase and osmundacetone: Molecular docking, multi-spectroscopy and dynamical simulation

Jiling Song; Minghui Chen; Fanlei Meng; Jiahui Chen; Zhanwei Wang; Yong Zhang; Jing Cui; Jing Wang; Dongfang Shi

doi:10.1016/j.saa.2023.122861

Studies on the interaction mechanism between xanthine oxidase and osmundacetone: Molecular docking, multi-spectroscopy and dynamical simulation

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Oct 15:299:122861. doi: 10.1016/j.saa.2023.122861. Epub 2023 May 13.

Authors

Jiling Song¹, Minghui Chen², Fanlei Meng³, Jiahui Chen¹, Zhanwei Wang¹, Yong Zhang⁴, Jing Cui⁵, Jing Wang⁶, Dongfang Shi⁵

Affiliations

¹ The College of Chemistry, Changchun Normal University, Changchun 130032, China.
² The College of Life Science, Changchun Normal University, Changchun 130032, China.
³ Institute of Agricultural Quality Standard and Testing Technology, Jilin Academy of Agricultural Sciences, Changchun 130033, China.
⁴ The College of Chemistry, Changchun Normal University, Changchun 130032, China; Nanguan Middle School, Honghua Gang District, Zunyi 563000, China.
⁵ The College of Life Science, Changchun Normal University, Changchun 130032, China; Institute of Science and Technology Innovation, Changchun Normal University, Changchun 130032, China.
⁶ The College of Chemistry, Changchun Normal University, Changchun 130032, China; The College of Life Science, Changchun Normal University, Changchun 130032, China; Institute of Science and Technology Innovation, Changchun Normal University, Changchun 130032, China. Electronic address: zixi21@163.com.

PMID: 37209475
DOI: 10.1016/j.saa.2023.122861

Abstract

Xanthine oxidase (XO) is a key enzyme in uric acid production, and its molybdopterin (Mo-Pt) domain is an important catalytic center when xanthine and hypoxanthine are oxidated. It is found that the extract of Inonotus obliquus has an inhibitory effect on XO. In this study, five key chemical compounds were initially identified using liquid chromatography-mass spectrometry (LC-MS), and two compounds, osmundacetone ((3E)-4-(3,4-dihydroxyphenyl)-3-buten-2-one) and protocatechuic aldehyde (3,4-dihydroxybenzaldehyde), were screened as the XO inhibitors by ultrafiltration technology. Osmundacetone bound XO strongly and competitively inhibited XO with a half-maximal inhibitory concentration of 129.08 ± 1.71 μM, and its inhibition mechanism, was investigated. Osmundacetone and XO via static quenching and spontaneously bound with XO with high affinity, primarily via hydrophobic interactions and hydrogen bonds. Molecular docking studies showed that osmundacetone was inserted into the Mo-Pt center and interacted with hydrophobic residues of Phe911, Gly913, Phe914, Ser1008, Phe1009, Thr1010, Val1011, and Ala1079 of XO. In summary, these findings suggest that provide theoretical basis for the research and development of XO inhibitors from Inonotus obliquus.

Keywords: Fluorescence quenching; Inhibition kinetics; Inonotus obliquus; Molecular docking; Osmundacetone; Xanthine oxidase inhibitor.

MeSH terms

Enzyme Inhibitors* / chemistry
Enzyme Inhibitors* / pharmacology
Molecular Docking Simulation
Spectrum Analysis
Xanthine Oxidase*

Substances

Xanthine Oxidase
osmundacetone
Enzyme Inhibitors

Supplementary concepts

Inonotus obliquus