Tao Sun1, Zhihua Wu1, Mengyao Luo1, Donghai Lin1, Chenyun Guo2. 1. Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Xiamen, 361005, Fujian, China. 2. Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Xiamen, 361005, Fujian, China. guochy78@xmu.edu.cn.
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.
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.
Authors: Inés Velázquez-Quesada; Angel J Ruiz-Moreno; Diana Casique-Aguirre; Charmina Aguirre-Alvarado; Fabiola Cortés-Mendoza; Marisol de la Fuente-Granada; Carlos García-Pérez; Sonia M Pérez-Tapia; Aliesha González-Arenas; Aldo Segura-Cabrera; Marco A Velasco-Velázquez Journal: Drug Des Devel Ther Date: 2020-05-12 Impact factor: 4.162