Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental
Mingsong Shi1, Yan Zhou1, Haoche Wei2
1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
Frontiers in Pharmacology
|May 1, 2023
Summary
Curcumin effectively binds to human salt-inducible kinase 3 (SIK3), showing potential for cancer treatment. This study details their interaction, identifying key residues and confirming curcumin
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Natural products, including curcumin, are explored for treating diseases like cancer.
- Human salt-inducible kinase 3 (SIK3) is a potential therapeutic target.
- Detailed investigation of curcumin-SIK3 interactions is lacking.
Purpose of the Study:
- To elucidate the binding models between curcumin and human SIK3 using computational and experimental methods.
- To identify key amino acid residues involved in curcumin-SIK3 binding.
- To evaluate the antiproliferative effects of curcumin on cancer cell lines.
Main Methods:
- Homology modeling
- Molecular docking
- Molecular dynamics simulations
- Binding free energy calculations
- Kinase assay
Main Results:
- The optimal binding model involved the open activity loop conformation of SIK3 and the ketoenol form of curcumin.
- Key residues (I72, V80, A93, Y144, A145, L195) were identified for curcumin binding.
- Curcumin demonstrated significant antiproliferative activity against MCF-7 and MDA-MB-23 cell lines with an IC50 of 131 nM.
Conclusions:
- This study provides a detailed understanding of curcumin-SIK3 interactions.
- The findings may guide the development of novel SIK3 inhibitors for cancer therapy.
