Tags

Type your tag names separated by a space and hit enter

Methylation of green tea polyphenols affects their binding to and inhibitory poses of the proteasome beta5 subunit.
Int J Mol Med. 2006 Oct; 18(4):625-32.IJ

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 beta5 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 beta5 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 beta5 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 beta5 subunit, which may then diminish their proteasomal chymotrypsin-inhibitory and, therefore, other biological activities.

Authors+Show Affiliations

The Prevention Program, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI 448201, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16964415

Citation

Daniel, Kenyon G., et al. "Methylation of Green Tea Polyphenols Affects Their Binding to and Inhibitory Poses of the Proteasome Beta5 Subunit." International Journal of Molecular Medicine, vol. 18, no. 4, 2006, pp. 625-32.
Daniel KG, Landis-Piwowar KR, Chen D, et al. Methylation of green tea polyphenols affects their binding to and inhibitory poses of the proteasome beta5 subunit. Int J Mol Med. 2006;18(4):625-32.
Daniel, K. G., Landis-Piwowar, K. R., Chen, D., Wan, S. B., Chan, T. H., & Dou, Q. P. (2006). Methylation of green tea polyphenols affects their binding to and inhibitory poses of the proteasome beta5 subunit. International Journal of Molecular Medicine, 18(4), 625-32.
Daniel KG, et al. Methylation of Green Tea Polyphenols Affects Their Binding to and Inhibitory Poses of the Proteasome Beta5 Subunit. Int J Mol Med. 2006;18(4):625-32. PubMed PMID: 16964415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylation of green tea polyphenols affects their binding to and inhibitory poses of the proteasome beta5 subunit. AU - Daniel,Kenyon G, AU - Landis-Piwowar,Kristin R, AU - Chen,Di, AU - Wan,Sheng Biao, AU - Chan,Tak-Hang, AU - Dou,Q Ping, PY - 2006/9/12/pubmed PY - 2006/12/9/medline PY - 2006/9/12/entrez SP - 625 EP - 32 JF - International journal of molecular medicine JO - Int J Mol Med VL - 18 IS - 4 N2 - 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 beta5 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 beta5 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 beta5 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 beta5 subunit, which may then diminish their proteasomal chymotrypsin-inhibitory and, therefore, other biological activities. SN - 1107-3756 UR - https://www.unboundmedicine.com/medline/citation/16964415/Methylation_of_green_tea_polyphenols_affects_their_binding_to_and_inhibitory_poses_of_the_proteasome_beta5_subunit_ L2 - http://www.spandidos-publications.com/ijmm/18/4/625 DB - PRIME DP - Unbound Medicine ER -