Pranlukast, a novel binding ligand of human Raf1 kinase inhibitory protein.
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.
['Sun|Tao|T|', 'Wu|Zhihua|Z|', 'Luo|Mengyao|M|', 'Lin|Donghai|D|', 'Guo|Chenyun|C|']
D002867:Chromones D006801:Humans D020935:MAP Kinase Signaling System D009682:Magnetic Resonance Spectroscopy D049488:Phosphatidylethanolamine Binding Protein D011485:Protein Binding D019908:Proto-Oncogene Proteins c-raf
Pranlukast hRKIP Fluorescence ERK phosphorylation level Ligand binding pocket Phosphatidylethanolamine binding protein Protein binding