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

Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, Ningbo, Zhejiang Province, People's Republic of China.
Journal of Molecular Modeling (Impact Factor: 1.87). 02/2011; 17(2):377-81. DOI: 10.1007/s00894-010-0738-0
Source: PubMed

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. Mg(2+) 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(I)(2+) 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(I)(2+) replacement with Li(+).

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