Insights into the inhibitory mechanism of purpurogallin on xanthine oxidase by multiple spectroscopic techniques and molecular docking
Insights into the inhibitory mechanism of purpurogallin on xanthine oxidase by multiple spectroscopic techniques and molecular docking
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DOI：
10.1016/j.molstruc.2020.129772
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发表时间：
2021-03-15
影响因子：
3.8
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Wang, Jin;Sun, Shiwei;Wang, Wei
采用多光谱法和分子对接分析研究了紫癜胆碱（Purpurogallin）对黄嘌呤氧化酶（xanthine oxidase， XO）的抑制机制。酶动力学分析表明，purpurogallin对XO活性具有较强的可逆混合型抑制作用，IC50值为（5.60 +/- 0.13）× 10(-6) mol.L-1。荧光滴定结果表明，purpurogallin通过自发猝灭和放热静态猝灭过程表现出强烈的荧光猝灭作用，其相互作用主要由氢键和范德华力驱动。同步荧光证实了紫癜胆碱增加了酪氨酸和色氨酸微环境的极性。圆二色性分析表明，purpurogallin诱导了XO的构象变化，α -螺旋结构增加，β -链和随机线圈结构减少。进一步的分子对接表明，purpurogallin占据XO的钼原子结构域，并与氨基酸残基Arg880、Thr1010、Val1011和Glu1261形成氢键。这些发现为理解紫胆碱对XO的抑制机制提供了全面的见解。(C) 2020 Elsevier B.V.版权所有
Purpurogallin, a benzotropolone containing natural compound found in nutgall and oak bark, was investigated for its inhibitory mechanism on xanthine oxidase (XO) by multispectroscopic methods and molecular docking analysis. The enzyme kinetic analysis showed that purpurogallin possessed a strong inhibition on XO activity in a reversible mixed type manner with IC50 value of (5.60 +/- 0.13) x 10(-6) mol.L-1. The results of fluorescence titration indicated that purpurogallin presented a strong fluorescence quenching effect through a spontaneous and exothermic static quenching procedure, and the interaction was predominately driven by hydrogen bonds and van der Waals forces. The synchronous fluorescence confirmed that purpurogallin increased the polarity of tyrosine and tryptophan microenvironment. Analysis of circular dichroism demonstrated that purpurogallin induced the conformational change of XO with increases in alpha-helix and reductions in beta-strand and random coil structures. Further molecular docking showed that purpurogallin occupied molybdenum atomic domain of XO, and formed hydrogen bonding with amino acid residues (Arg880, Thr1010, Val1011 and Glu1261). These findings provide comprehensive insights into understanding the inhibitory mechanism of purpurogallin on XO. (C) 2020 Elsevier B.V. All rights reserved.