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Identification of Potential Inhibitors of CalciumCalmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents
Joint Authors
Al-Ajmi, Mohamed F.
Hussain, Afzal
Hassan, Imtaiyaz
Ahmad, Faizan
Islam, Asimul
Gupta, Preeti
Khan, Shama
Fakhar, Zeynab
Rehman, Md. Tabish
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-17
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is an upstream regulator of CaMKK-CaMKIV signaling cascade that activates various transcription factors, thereby regulating several cellular activities including, neuronal communication and immune response.
Owing to the abnormal expression in cancer and neurodegenerative diseases, the CaMKIV has been considered a potential drug target.
In the present study, we checked the binding affinity of plant-derived natural compounds viz., quercetin, ellagic acid (EA), simvastatin, capsaicin, ursolic acid, DL-α-tocopherol acetate, and limonin towards CaMKIV.
Molecular docking and fluorescence binding studies showed that EA and quercetin bind to the CaMKIV with a considerable affinity in comparison to other compounds.
Enzyme inhibition assay revealed that both EA and quercetin inhibit CaMKIV activity with their IC50 values in the micromolar range.
To get atomistic insights into the mode of interactions, inhibition mechanism, and the stability of the CaMKIV-ligand complex, a 100 ns MD simulation analysis was performed.
Both EA and quercetin bind to the catalytically important residues of active site pocket of CaMKIV forming enough stabilizing interactions presumably inhibiting enzyme activity.
Moreover, no significant structural change in the CaMKIV was observed upon binding of EA and quercetin.
In conclusion, this study illustrates the application of phytoconstituents in the development of therapeutic molecules targeting CaMKIV having implications in cancer and neurodegenerative diseases after in vivo validation.
American Psychological Association (APA)
Gupta, Preeti& Khan, Shama& Fakhar, Zeynab& Hussain, Afzal& Rehman, Md. Tabish& Al-Ajmi, Mohamed F.…[et al.]. 2020. Identification of Potential Inhibitors of CalciumCalmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203879
Modern Language Association (MLA)
Gupta, Preeti…[et al.]. Identification of Potential Inhibitors of CalciumCalmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1203879
American Medical Association (AMA)
Gupta, Preeti& Khan, Shama& Fakhar, Zeynab& Hussain, Afzal& Rehman, Md. Tabish& Al-Ajmi, Mohamed F.…[et al.]. Identification of Potential Inhibitors of CalciumCalmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203879
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203879