Role of Mg²⁺ ions in protein kinase phosphorylation: insights from molecular dynamics simulations of ATP-kinase complexes

Author： Yu Lu Xu Lizhe Xu Min Wan Bo Yu Long Huang Qiang

Publisher： Taylor & Francis Ltd

ISSN： 0892-7022

Source： Molecular Simulation, Vol.37, Iss.14, 2011-12, pp. : 1143-1150

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Abstract

Phosphorylation of protein kinases (PKs) plays a central role in the signal transduction of cells by transferring a phosphate group from adenosine triphosphate (ATP) to the side chains of particular serine, threonine or tyrosine residues of substrates. Previous studies have shown that Mg²⁺ ions are crucial for the formation of transition state of phosphoryl transfer reaction. However, the roles of Mg²⁺ ions in other steps of phosphorylation remain poorly understood. Here, we performed molecular dynamics simulations to study the interactions of ATP with PKs in the presence and the absence of Mg²⁺ ions in the active sites, respectively. Affinity analysis showed that the binding-free energies of ATP to the PK active sites in the presence of Mg²⁺ ions are lower than those in the absence of Mg²⁺ ions, suggesting that Mg²⁺ ions in the active sites could enhance the binding affinities of ATP to the PKs. This enhancement is mainly attributed to the electrostatic interactions induced by Mg²⁺ ions. Thus, this study shows that Mg²⁺ ions also play a very important role in the binding of ATP to PKs, and thereby gains a better understanding of how Mg²⁺ ions function in protein phosphorylation.