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有读书笔记Epigallocatechin-3-gallate and penta-O-galloyl-beta-D-glucose inhibit protein phosphatase-1

阿平 添加于 2012-1-22 22:26 | 1709 次阅读 | 0 个评论

  •  作 者

    Kiss A, Becsi B, Kolozsvari B, Komaromi I, Kover KE, Erdodi F

  •  摘 要

    Protein phosphatase-1 (PP1) and -2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study we show that epigallocatechin-3-gallate (EGCG) and penta-O-galloyl-beta-D-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of recombinant delta isoform and native PP1 catalytic subunit (PP1delta and PP1c) with IC(50) values of 0.47-1.35 muM and 0.26-0.4 muM, respectively. EGCG and PGG inhibits PP2Ac less potently with IC(50) values of 15 muM and 6.6 muM, respectively. Structure-inhibitory potency relationship of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c is characterized by NMR- and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic centre of PP1c partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long term treatments (24 h) with these compounds and other catechins suppress the viability of HeLa cells with relative effectiveness reminiscent of their in vitro PP1c inhibitory potencies. The above data imply that the phosphatase inhibitory features of these polyphenols may be implicated in the wide spectra of their physiological influences.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: The FEBS Journal
    • 期刊缩写: FEBS J
    • 期卷页: 2012年
    • 地址: Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Hungary Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Research Center for Molecular Medicine, University of Debrecen, Hungary Thrombosis, Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Hungary Department of Chemistry, University of Debrecen, Hungary
    • ISBN: 1742-464X

  •  标 签

    PP1 

  • 相关链接 DOI URL 

  •  阿平 的文献笔记  订阅

    原来多酚类药物还有抑制PP1的作用
    绿茶中的茶多酚和丹宁中的多酚均可以抑制PP1，虽然同时也抑制PP2A，并且IC50的值不算太完美，但这毕竟有时蛋白磷酸酶领域的一个好工具。而且多酚类往往有不少参与抗癌的作用，既然茶多酚能够抑制PP1，至少不能排除其抗癌机制是来源于此。
    另外，多酚类抑制蛋白磷酸酶的机制可能还不是很特意，会产生很多其他意想不到的作用，我想以前那么多相关研究已经说明问题了，所以要用在研究蛋白磷酸酶功能这方面，恐怕还不是最佳选择，我们实验室不日将发表一个更特异，更好的PP1抑制工具，敬请期待！
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