Curcumin specifically binds to the human calcium-calmodulin-dependent protein kinase IV: fluorescence and molecular dynamics simulation studies.
Calcium-calmodulin-dependent protein kinase IV (CAMK4) plays significant role in the regulation of calcium-dependent gene expression, and thus, it is involved in varieties of cellular functions such as cell signaling and neuronal survival. On the other hand, curcumin, a naturally occurring yellow bioactive component of turmeric possesses wide spectrum of biological actions, and it is widely used to treat atherosclerosis, diabetes, cancer, and inflammation. It also acts as an antioxidant. Here, we studied the interaction of curcumin with human CAMK4 at pH 7.4 using molecular docking, molecular dynamics (MD) simulations, fluorescence binding, and surface plasmon resonance (SPR) methods. We performed MD simulations for both neutral and anionic forms of CAMK4-curcumin complexes for a reasonably long time (150 ns) to see the overall stability of the protein-ligand complex. Molecular docking studies revealed that the curcumin binds in the large hydrophobic cavity of kinase domain of CAMK4 through several hydrophobic and hydrogen-bonded interactions. Additionally, MD simulations studies contributed in understanding the stability of protein-ligand complex system in aqueous solution and conformational changes in the CAMK4 upon binding of curcumin. A significant increase in the fluorescence intensity at 495 nm was observed (λexc = 425 nm), suggesting a strong interaction of curcumin to the CAMK4. A high binding affinity (KD = 3.7 × 10(-8) ± .03 M) of curcumin for the CAMK4 was measured by SPR further indicating curcumin as a potential ligand for the CAMK4. This study will provide insights into designing a new inspired curcumin derivatives as therapeutic agents against many life-threatening diseases.
a Department of Chemistry , Jamia Millia Islamia , Jamia Nagar, New Delhi 110025 , India.
Nasimul
N
Hoda
b Centre for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia , Jamia Nagar, New Delhi 110025 , India.
Huma
H
Naz
c Department of Chemistry , Babasaheb Bhimrao Ambedkar Bihar University , Muzaffarpur , Bihar 842002 , India.
Ehtesham
E
Jameel
d Supercomputing Facility for Bioinformatics & Computational Biology , Indian Institute of Technology , Hauz Khas, New Delhi 110016 , India.|e Department of Chemistry , Indian Institute of Technology , Hauz Khas, New Delhi 110016 , India.
Ashutosh
A
Shandilya
f Department of Biophysics , All India Institute of Medical Sciences , New Delhi 110029 , India.
Sharmistha
S
Dey
b Centre for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia , Jamia Nagar, New Delhi 110025 , India.
Md Imtaiyaz
MI
Hassan
b Centre for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia , Jamia Nagar, New Delhi 110025 , India.
Faizan
F
Ahmad
d Supercomputing Facility for Bioinformatics & Computational Biology , Indian Institute of Technology , Hauz Khas, New Delhi 110016 , India.|e Department of Chemistry , Indian Institute of Technology , Hauz Khas, New Delhi 110016 , India.
B
B
Jayaram
D001665:Binding Sites; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055550:Protein Stability; D013816:Thermodynamics
D008024:Ligands; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D003474:Curcumin
calcium–calmodulin-dependent protein kinase IV; curcumin; docking; drug target; high affinity ligand; molecular dynamics simulation