Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/12748
Title: Methylation of green tea polyphenols affects their binding to and inhibitory poses of the proteasome β5 subunit
Authors: Daniel, KG
Landis-Piwowar, KR
Chen, D
Wan, SB
Chan, TH
Dou, QP
Keywords: (-)-epicatechin-3-gallate
Cancer
Computer modeling
Docking
Methylation
Proteasome inhibitors
Tea polyphenols
(-)-epigallocatechin gallate
Issue Date: 2006
Publisher: Spandidos Publications
Source: International journal of molecular medicine, 2006, v. 18, no. 4, p. 625-632 How to cite?
Journal: International journal of molecular medicine 
Abstract: Previously, we showed that ester carbon-containing tea polyphenols, including (-)-epigallocatechin gallate [(-)-EGCG] and (-)-epicatechin-3-gallate [(-)-ECG], potently inhibit proteasomal chymotrypsin-like activity. In addition, our in silico docking study suggested that a particular pose of (-)-EGCG could lead to potential covalent modification of the N-terminal threonine (Thr 1) of the proteasome β5 subunit in the chymotrypsin-like active site. It has been suggested that some major biotransformation reactions, such as methylation, could result in reduced biological activity of (-)-EGCG in vivo. We hypothesize that methylation reduces binding of (-)-EGCG to the β5 subunit of the proteasome and, therefore, decreases its proteasomal chymotrypsin-like- inhibitory potency. Here, we report that, while methylation has no effect on nucleophilic susceptibility of (-)-EGCG and (-)-ECG, it may disrupt the ability of these polyphenols to interact with Thr 1 of the proteasome β5 subunit. In silico docking shows that methylation results in the tea polyphenols' ester carbon being moved away or blocked entirely from Thr 1. Additionally, methylation impairs the ability of (-)-EGCG and (-)-ECG to dock in a consistent low energy pose. These observations, no change in nucleophilic susceptibility, moving or blocking the ester carbon from Thr 1, and lack of a consistent docking pose, suggest that methylation disrupts the ability of (-)-EGCG and (-)-ECG to bind to the proteasome β5 subunit, which may then diminish their proteasomal chymotrypsin-inhibitory and, therefore, other biological activities.
URI: http://hdl.handle.net/10397/12748
ISSN: 1107-3756
EISSN: 1791-244X
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