Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities
Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities
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DOI：
10.1016/j.chembiol.2007.03.007
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发表时间：
2007-04-01
影响因子：
--
通讯作者：
Bianchi, Marco E.
中科院分区：
文献类型：
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作者：
Mollica, Luca;De Marchis, Francesco;Bianchi, Marco E.
高迁移率族蛋白1（HMGB1）是一种核组分，但在细胞外，它作为一种信号分子参与急性和慢性炎症，例如败血症和关节炎。因此，HMGB1抑制剂的鉴定具有重要的实验和临床意义。我们发现，在临床上使用的天然抗炎和抗病毒三萜，抑制HMGB1化学引诱和促有丝分裂活性，并有一个弱的抑制作用，其核内DNA结合功能。核磁共振和荧光研究表明，HMGB1（Kd类似于150 μ M），与两个HMG盒的两个臂形成的两个浅凹表面相互作用，直接结合到HMGB1。我们的研究结果部分解释了HMGB1的抗炎特性，并可能指导具有改善HMGB1结合特性的新衍生物的设计。
High-mobility group box 1 protein (HMGB1) is a nuclear component, but extracellularly it serves as a signaling molecule involved in acute and chronic inflammation, for example in sepsis and arthritis. The identification of HMGB1 inhibitors is therefore of significant experimental and clinical interest. We show that glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function. NMR and fluorescence studies indicate that glycyrrhizin binds directly to HMGB1 (K-d similar to 150 mu M), interacting with two shallow concave surfaces formed by the two arms of both HMG boxes. Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties.