Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods.
Mingsong Shi, Yan Zhou, Haoche Wei, Xinyu Zhang, Meng Du, Yanting Zhou, Yuan Yin, Xinghui Li, Xinyi Tang, Liang Sun, Dingguo Xu, Xiaoan Li
Author Information
Mingsong Shi: NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
Yan Zhou: NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
Haoche Wei: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xinyu Zhang: West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
Meng Du: College of Chemistry, MOE Key Laboratory of Green Chemistry and Technology, Sichuan University, Chengdu, Sichuan, China.
Yanting Zhou: Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Yuan Yin: NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
Xinghui Li: West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
Xinyi Tang: West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
Dingguo Xu: College of Chemistry, MOE Key Laboratory of Green Chemistry and Technology, Sichuan University, Chengdu, Sichuan, China.
Xiaoan Li: NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
Natural products are widely used for treating mitochondrial dysfunction-related diseases and cancers. Curcumin, a well-known natural product, can be potentially used to treat cancer. Human salt-induced kinase 3 (SIK3) is one of the target proteins for curcumin. However, the interactions between curcumin and human SIK3 have not yet been investigated in detail. In this study, we studied the binding models for the interactions between curcumin and human SIK3 using computational tools such as homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations. The open activity loop conformation of SIK3 with the ketoenol form of curcumin was the optimal binding model. The I72, V80, A93, Y144, A145, and L195 residues played a key role for curcumin binding with human SIK3. The interactions between curcumin and human SIK3 were also investigated using the kinase assay. Moreover, curcumin exhibited an IC (half-maximal inhibitory concentration) value of 131 nM, and it showed significant antiproliferative activities of 9.62 ± 0.33 µM and 72.37 ± 0.37 µM against the MCF-7 and MDA-MB-23 cell lines, respectively. This study provides detailed information on the binding of curcumin with human SIK3 and may facilitate the design of novel salt-inducible kinases inhibitors.
