Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/99837
Title: Structural insights into the dual-targeting mechanism of Nutlin-3
Authors: Shin, Jae-Sun
Ha, Ji-Hyang
He, Fahu
Muto, Yutaka
Ryu, Kyoung-Seok
Yoon, Ho Sup
Kang, Sunghyun
Park, Sung Goo
Park, Byoung Chul
Choi, Sang-Un
Chi, Seung-Wook
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Shin, J.-S., Ha, J.-H., He, F., Muto, Y., Ryu, K.-S., Yoon, H. S., et al. (2012). Structural insights into the dual-targeting mechanism of Nutlin-3. Biochemical and Biophysical Research Communications, 420(1), 48-53.
Series/Report no.: Biochemical and biophysical research communications
Abstract: Multi-targeting therapy is an emerging strategy of drug discovery to improve therapeutic efficacy, safety and resistance profiles. In this study, we monitored the binding of a potent MDM2 inhibitor Nutlin-3 with anti-apoptotic Bcl-2 family proteins using NMR spectroscopy. Our results showed the universal binding of Nutlin-3 with diverse anti-apoptotic Bcl-2 family proteins. Taken together with the binding data for Nutlin-3 analogs, the structural model of the Bcl-XL/Nutlin-3 complex showed that the binding mode of Nutlin-3 resembles that of the Bcl-XL/Bcl-2 inhibitors, suggesting the molecular mechanism of transcription-independent mitochondrial apoptosis by Nutlin-3. Finally, our structural comparison provides structural insights into the dual-targeting mechanism of how Nutlin-3 can bind to two different target proteins, MDM2 and anti-apoptotic Bcl-2 family proteins in a similar manner.
URI: https://hdl.handle.net/10356/99837
http://hdl.handle.net/10220/11029
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2012.02.113
Schools: School of Biological Sciences 
Rights: © 2012 Elsevier lnc.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

SCOPUSTM   
Citations 20

22
Updated on Feb 24, 2024

Web of ScienceTM
Citations 20

20
Updated on Oct 29, 2023

Page view(s) 20

692
Updated on Feb 27, 2024

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.