Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0024122
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dc.titleC-terminal Substitution of MDM2 interacting peptides modulates binding affinity by distinctive mechanisms
dc.contributor.authorBrown, C.J.
dc.contributor.authorDastidar, S.G.
dc.contributor.authorQuah, S.T.
dc.contributor.authorLim, A.
dc.contributor.authorChia, B.
dc.contributor.authorVerma, C.S.
dc.date.accessioned2014-10-27T08:25:13Z
dc.date.available2014-10-27T08:25:13Z
dc.date.issued2011
dc.identifier.citationBrown, C.J., Dastidar, S.G., Quah, S.T., Lim, A., Chia, B., Verma, C.S. (2011). C-terminal Substitution of MDM2 interacting peptides modulates binding affinity by distinctive mechanisms. PLoS ONE 6 (8) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0024122
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/100380
dc.description.abstractThe complex between the proteins MDM2 and p53 is a promising drug target for cancer therapy. The residues 19-26 of p53 have been biochemically and structurally demonstrated to be a most critical region to maintain the association of MDM2 and p53. Variation of the amino acid sequence in this range obviously alters the binding affinity. Surprisingly, suitable substitutions contiguous to this region of the p53 peptides can yield tightly binding peptides. The peptide variants may differ by a single residue that vary little in their structural conformations and yet are characterized by large differences in their binding affinities. In this study a systematic analysis into the role of single C-terminal mutations of a 12 residue fragment of the p53 transactivation domain (TD) and an equivalent phage optimized peptide (12/1) were undertaken to elucidate their mechanistic and thermodynamic differences in interacting with the N-terminal of MDM2. The experimental results together with atomistically detailed dynamics simulations provide insight into the principles that govern peptide design protocols with regard to protein-protein interactions and peptidomimetic design. © 2011 Brown et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0024122
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1371/journal.pone.0024122
dc.description.sourcetitlePLoS ONE
dc.description.volume6
dc.description.issue8
dc.description.page-
dc.identifier.isiut000294680800056
dc.published.statePublished
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