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The effect of Li+ on GSK-3 inhibition: Molecular dynamics simulation

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Abstract

Glycogen synthase kinase-3 (GSK-3) is a kind of serine-threonine protein kinase. It places important roles in several signaling pathways and it is a key therapeutic target for a number of diseases, such as diabetes, cancer, Alzheimer’s disease and chronic inflammation. Mg2+ ions which interact with ATP are conserved in GSK. They are important in phosphoryl transfer. Li+ is an inhibitor for GSK-3. It is used to treat bipolar mood disorder. This paper illustrates the effect of Li+ on GSK-3. When Mg 2+I is replaced by Li+, the atom fluctuation of GSK-3 will rise, and the in-line phosphoryl transfer mechanism is probably demolished and the binding of pre-phosphorylated substrates may be disturbed. All the results we obtained clearly suggest that inhibition to GSK-3 is caused by the Mg 2+I replacement with Li+.

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Acknowledgments

This work was supported by grants from National High Technology Research and Development Program of China (863 Program, 2007AA02Z301), Natural Science Foundation of China (No.20803063).

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Authors and Affiliations

  1. Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, Ningbo, Zhejiang Province, 315100, People’s Republic of China

    Hao Sun, Yong-jun Jiang, Qing-sen Yu, Cheng-cai Luo & Jian-wei Zou

  2. Southwest Forestry College, Kunming, Yunnan Province, 650224, People’s Republic of China

    Hao Sun

  3. Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang Province, 310027, People’s Republic of China

    Qing-sen Yu

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  1. Hao Sun
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  2. Yong-jun Jiang
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  3. Qing-sen Yu
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  4. Cheng-cai Luo
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  5. Jian-wei Zou
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Correspondence to Yong-jun Jiang.

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Sun, H., Jiang, Yj., Yu, Qs. et al. The effect of Li+ on GSK-3 inhibition: Molecular dynamics simulation. J Mol Model 17, 377–381 (2011). https://doi.org/10.1007/s00894-010-0738-0

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  • DOI: https://doi.org/10.1007/s00894-010-0738-0

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