The effect of Li+ on GSK-3 inhibition: molecular dynamics simulation.
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(+).
Sun
Hao
H
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.
Jiang
Yong-jun
YJ
Yu
Qing-sen
QS
Luo
Cheng-cai
CC
Zou
Jian-wei
JW
D000255:Adenosine Triphosphate / Q000737:chemistry; D003198:Computer Simulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006860:Hydrogen Bonding; D018020:Lithium Compounds / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008968:Molecular Conformation / Q000187:drug effects; D056004:Molecular Dynamics Simulation; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction
D018020:Lithium Compounds; D000255:Adenosine Triphosphate; D038362:Glycogen Synthase Kinase 3; D008274:Magnesium
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