mirage

Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins

DSpace/Manakin Repository

 

Search DR-NTU


Advanced Search Subject Search

Browse

My Account

Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins

Show full item record

Title: Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins
Author: Ha, Ji-Hyang; Won, Eun-Young; Shin, Jae-Sun; Jang, Mi; Ryu, Kyoung-Seok; Baek, Kwanghee; Park, Sung Goo; Park, Byoung Chul; Yoon, Ho Sup; Chi, Seung-Wook
Copyright year: 2011
Abstract: The identification of off-target binding of drugs is a key to repositioning drugs to new therapeutic categories. Here we show the universal interactions of the p53 transactivation domain (p53TAD) with various antiapoptotic Bcl-2 family proteins via a mouse double minute 2 (MDM2) binding motif, which play an important role in transcription-independent apoptotic pathways of p53. Interestingly, our structural studies reveal that the anti-apoptotic Bcl-2 family proteins and MDM2 share a similar mode of interaction with the p53TAD. On the basis of this close molecular mimicry, our NMR results demonstrate that the potent MDM2 antagonists Nutlin-3 and PMI bind to the anti-apoptotic Bcl-2 family proteins in a manner analogous to that with the p53TAD.
Subject: DRNTU::Science::Biological sciences.
Type: Journal Article
Series/ Journal Title: Journal of the American chemical society
School: School of Biological Sciences
Rights: © 2011 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of the American Chemical Society , American Chemical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.1021/ja109521f.
Version: Accepted version

Files in this item

Files Size Format View
4. Molecular Mi ... Bcl-2 Family Proteins.pdf 663.4Kb PDF View/Open
   

DOI Query

- Get published version (via Digital Object Identifier)
   

This item appears in the following Collection(s)

Show full item record

Statistics

Total views

All Items Views
Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins 210

Total downloads

All Bitstreams Views
4. Molecular Mimicry-Based Repositioning of Nutlin-3 to Anti-Apoptotic Bcl-2 Family Proteins.pdf 141

Top country downloads

Country Code Views
United States of America 71
China 17
Singapore 15
Korea 10
Japan 4

Top city downloads

city Views
Mountain View 53
Beijing 13
Singapore 13
Seoul 9
Redwood City 5