3OOB

Structural and functional insights of directly targeting Pin1 by Epigallocatechin-3-gallate

3OOB の概要

• エントリーDOI: 10.2210/pdb3oob/pdb
• 関連するPDBエントリー: 1F8A 1PIN 2ITK 2Q5A
• 分子名称: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, SULFATE ION, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (5 entities in total)
• 機能のキーワード: ww domain-like peptidyl prolyl isomerase, phosphorylation-dependent cis/trans isomerase, proteins with pser/pthr-pro motif, isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q13526
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20261.31

構造登録者

Urusova, D.V.,Shim, J.-H.,Kim, D.-J.,Jung, S.K.,Zykova, T.A.,Bode, A.M.,Dong, Z. (登録日: 2010-08-30, 公開日: 2011-08-17, 最終更新日: 2024-02-21)

主引用文献

Urusova, D.V.,Shim, J.H.,Kim, D.J.,Jung, S.K.,Zykova, T.A.,Carper, A.,Bode, A.M.,Dong, Z.
Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.
Cancer Prev Res (Phila), 4:1366-1377, 2011

PubMed Abstract: The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate-induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.

PubMed: 21750208
DOI: 10.1158/1940-6207.CAPR-11-0301

実験手法

X-RAY DIFFRACTION (1.89 Å)