Abstract
Objectives
To study the binding of pranlukast to hRKIP and its regulatory role in the Raf1/MEK/ERK signal pathway.
Results
NMR and fluorescence experiments demonstrated hRKIP could bind pranlukast with a binding constant of 1016 mM−1. Residues (Y81, S109 and Y181) on the conserved ligand-binding pocket of hRKIP played a crucial role in binding pranlukast, and their mutations reduced the binding affinity more than 85 %. Furthermore, 25 μM pranlukast could up-regulate the ERK phosphorylation by about 17 %.
Conclusion
Pranlukast may be used as a potential drug precursor for treating hRKIP involved diseases.
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Acknowledgments
This work was supported by the Natural Science Foundation of China (No. 31470034) and the Fundamental Research Funds for the Central Universities (No. 20720160033). We thank Haiping Zhang and Professor Zhiliang Ji from School of Life Sciences, Xiamen University for their help in virtual screening.
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Sun, T., Wu, Z., Luo, M. et al. Pranlukast, a novel binding ligand of human Raf1 kinase inhibitory protein. Biotechnol Lett 38, 1375–1380 (2016). https://doi.org/10.1007/s10529-016-2117-0
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DOI: https://doi.org/10.1007/s10529-016-2117-0