3OOB

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

Summary for 3OOB

• Entry DOI: 10.2210/pdb3oob/pdb
• Related: 1F8A 1PIN 2ITK 2Q5A
• Descriptor: 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)
• Functional Keywords: ww domain-like peptidyl prolyl isomerase, phosphorylation-dependent cis/trans isomerase, proteins with pser/pthr-pro motif, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q13526
• Total number of polymer chains: 1
• Total formula weight: 20261.31

Authors

Urusova, D.V.,Shim, J.-H.,Kim, D.-J.,Jung, S.K.,Zykova, T.A.,Bode, A.M.,Dong, Z. (deposition date: 2010-08-30, release date: 2011-08-17, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.89 Å)