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Open AccessArticle

Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway

1
UPM-MAKNA Cancer Research Laboratory, Institute of Biosciences, University Putra Malaysia, 43400 Serdang, Malaysia
2
Faculty of Pharmaceutical Sciences, UCSI University, 1-Jalan Menara Gading, Taman Connaught, Cheras, 56000 Kuala Lumpur, Malaysia
3
Department of Microbiology and Pathology, Faculty of Veterinary Medicine, University Putra Malaysia, 43400 Serdang, Malaysia
4
Department of Chemistry, Faculty of Science, University Putra Malaysia, 43400 Serdang, Malaysia
5
Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Selangor, Malaysia
6
Department of Chemistry, Faculty of Science, University Malaya, Petaling Jaya, 50603 Selangor, Malaysia
*
Authors to whom correspondence should be addressed.
Academic Editor: Christo Christov
Int. J. Mol. Sci. 2015, 16(2), 2747-2766; https://doi.org/10.3390/ijms16022747
Received: 24 October 2014 / Accepted: 7 January 2015 / Published: 26 January 2015
(This article belongs to the Collection Proteins and Protein-Ligand Interactions)
Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis. View Full-Text
Keywords: zerumbone; Inhibitor of κ-B kinase (IKK); nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB); CHARMm based docking software (CDOCKER); molecular docking zerumbone; Inhibitor of κ-B kinase (IKK); nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB); CHARMm based docking software (CDOCKER); molecular docking
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Fatima, A.; Abdul, A.B.H.; Abdullah, R.; Karjiban, R.A.; Lee, V.S. Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway. Int. J. Mol. Sci. 2015, 16, 2747-2766.

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