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

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

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dc.contributor.author Ha, Ji-Hyang.
dc.contributor.author Won, Eun-Young.
dc.contributor.author Shin, Jae-Sun.
dc.contributor.author Jang, Mi.
dc.contributor.author Ryu, Kyoung-Seok.
dc.contributor.author Baek, Kwanghee.
dc.contributor.author Park, Sung Goo.
dc.contributor.author Park, Byoung Chul.
dc.contributor.author Yoon, Ho Sup.
dc.contributor.author Chi, Seung-Wook.
dc.date.accessioned 2012-10-09T06:11:44Z
dc.date.available 2012-10-09T06:11:44Z
dc.date.copyright 2011
dc.date.issued 2012-10-09
dc.identifier.citation Ha, J. H., Won, E. Y., Shin, J. S., Jang, M., Ryu, K. S., Baek, K., et al. (2011). Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins. Journal of the American chemical society, 133(5), 1244-1247.
dc.identifier.uri http://hdl.handle.net/10220/8736
dc.description.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.
dc.language.iso en
dc.relation.ispartofseries Journal of the American chemical society
dc.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.
dc.subject DRNTU::Science::Biological sciences.
dc.title Molecular mimicry-based repositioning of Nutlin-3 to anti-apoptotic Bcl-2 family proteins.
dc.type Journal Article
dc.contributor.school School of Biological Sciences
dc.identifier.doi http://dx.doi.org/10.1021/ja109521f
dc.description.version Accepted version

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