Abstract
Protein kinase CK2 (casein kinase 2) is a multifunctional serine/threonine kinase that is involved in a broad range of physiological events. The decreased affinity of Emodin binding to human CK2α resulting from single-point mutation of Val66 to Ala (V66A) has been demonstrated by experimental mutagenesis. Molecular dynamics (MD) simulations and energy analysis were performed on wild type (WT) and V66A mutant CK2α-Emodin complexes to investigate the subtle influences of amino acid replacement on the structure of the complex. The structure of CK2α and the orientation of Emodin undergo changes to different degrees in V66A mutant. The affected positions in CK2α are mainly distributed over the glycine-rich loop (G-loop), the α-helix and the loop located at the portion between G-loop and α-helix (C-loop). Based on the coupling among these segments, an allosteric mechanism among the C-loop, the G-loop and the deviated Emodin is proposed. Additionally, an estimated energy calculation and residue-based energy decomposition also indicate the lower instability of V66A mutant in contrast to WT, as well as the unfavorable energetic influences on critical residue contributions.
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Acknowledgments
This work was funded by China Postdoctoral Science Foundation funded project (No. 20090450271) and Beijing Natural Science Foundation (8072006). We acknowledge Professor David Case for the kind gift of AMBER 10 software.
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Zhang, N., Zhong, R. Structural basis for decreased affinity of Emodin binding to Val66-mutated human CK2α as determined by molecular dynamics. J Mol Model 16, 771–780 (2010). https://doi.org/10.1007/s00894-009-0582-2
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DOI: https://doi.org/10.1007/s00894-009-0582-2