dc.contributor.authorShin, Jae-Sun
dc.contributor.authorHa, Ji-Hyang
dc.contributor.authorHe, Fahu
dc.contributor.authorMuto, Yutaka
dc.contributor.authorRyu, Kyoung-Seok
dc.contributor.authorYoon, Ho Sup
dc.contributor.authorKang, Sunghyun
dc.contributor.authorPark, Sung Goo
dc.contributor.authorPark, Byoung Chul
dc.contributor.authorChoi, Sang-Un
dc.contributor.authorChi, Seung-Wook
dc.identifier.citationShin, 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.en_US
dc.description.abstractMulti-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.en_US
dc.relation.ispartofseriesBiochemical and biophysical research communicationsen_US
dc.rights© 2012 Elsevier lnc.en_US
dc.subjectDRNTU::Science::Biological sciences
dc.titleStructural insights into the dual-targeting mechanism of Nutlin-3en_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record