Glycoside hydrolase family 18 and 20 enzymes are novel targets of the traditional medicine berberine

文献类型： 外文期刊

第一作者： Liu, Tian

作者： Liu, Tian;Zhou, Yong;Yang, Qing;Duan, Yanwei;Liu, Tian;Zhou, Yong;Yang, Qing;Dou, Tongyi;Yang, Qing

作者机构：

关键词： glycoside hydrolase; chitinase; inhibitor; protein crystallization; human; insect; -N-acetyl-D-hexosaminidase; berberine

期刊名称：JOURNAL OF BIOLOGICAL CHEMISTRY （ 影响因子：5.157； 五年影响因子：5.041 ）

ISSN： 0021-9258

年卷期： 2018 年 293 卷 40 期

页码：

收录情况： SCI

摘要： Berberine is a traditional medicine that has multiple medicinal and agricultural applications. However, little is known about whether berberine can be a bioactive molecule toward carbohydrate-active enzymes, which play numerous vital roles in the life process. In this study, berberine and its analogs were discovered to be competitive inhibitors of glycoside hydrolase family 20 -N-acetyl-d-hexosaminidase (GH20 Hex) and GH18 chitinase from both humans and the insect pest Ostrinia furnacalis. Berberine and its analog SYSU-1 inhibit insect GH20 Hex from O. furnacalis (OfHex1), with K-i values of 12 and 8.5 m, respectively. Co-crystallization of berberine and its analog SYSU-1 in complex with OfHex1 revealed that the positively charged conjugate plane of berberine forms - stacking interactions with Trp(490), which are vital to its inhibitory activity. Moreover, the 1,3-dioxole group of berberine binds an unexplored pocket formed by Trp(322), Trp(483), and Val(484), which also contributes to its inhibitory activity. Berberine was also found to be an inhibitor of human GH20 Hex (HsHexB), human GH18 chitinase (HsCht and acidic mammalian chitinase), and insect GH18 chitinase (OfChtI). Besides GH18 and GH20 enzymes, berberine was shown to weakly inhibit human GH84 O-GlcNAcase (HsOGA) and Saccharomyces cerevisiae GH63 -glucosidase I (ScGluI). By analyzing the published crystal structures, berberine was revealed to bind with its targets in an identical mechanism, namely via - stacking and electrostatic interactions with the aromatic and acidic residues in the binding pockets. This paper reports new molecular targets of berberine and may provide a berberine-based scaffold for developing multitarget drugs.

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