Investigation of molecular mechanism of recognition between citral and MARK4: A newer therapeutic approach to attenuate cancer cell progression

Farha Naz, Faez Iqbal Khan, Taj Mohammad, Parvez Khan, Saaliqa Manzoor, Gulam Mustafa Hasan, Kevin A. Lobb, Suaib Luqman, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Microtubule affinity regulating kinase 4 (MARK4) is a member of AMP-activated protein kinase, found to be involved in apoptosis, inflammation and many other regulatory pathways. Since, its aberrant expression is directly associated with the cell cycle and thus cancer. Therefore, MARK4 is being considered as a potential drug target for cancer therapy. Here, we investigated the mechanism of inhibition of MARK4 activity by citral. Docking studies suggested that citral effectively binds to the active site cavity, and complex is stabilized by several interactions. We further performed molecular dynamics simulation of MARK4-citral complex under explicit water condition for 100 ns and observed that binding of citral to MARK4 was quite stable. Fluorescence binding studies suggested that citral strongly binds to MARK4 and thereby inhibits its enzyme activity which was measured by the kinase inhibition assay. We further performed MTT assay and observed that citral inhibits proliferation of breast cancer cell line MCF-7. This work provides a newer insight into the use of citral as novel cancer therapeutics through the MARK4 inhibition.

Original languageEnglish
Pages (from-to)2580-2589
Number of pages10
JournalInternational Journal of Biological Macromolecules
Volume107
DOIs
Publication statusPublished - Feb 2018
Externally publishedYes

Keywords

  • Anticancer activity
  • Citral: medicinal plants
  • High-affinity ligands
  • Kinase inhibition assay
  • MAP/microtubule affinity-regulating kinase
  • Molecular dynamics simulation

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