4owi

peptide structure

spinqualitylabelsall models 4owi, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4owi is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Reactivation of the p53 pathway by a potential therapeutic antagonist, which inhibits HDM2 and HDMX, is an attractive strategy for drug development in oncology. Developing blockers towards conserved hydrophobic pockets of both HDMs has mainly focused on small synthetic compounds; however, this approach has proved challenging. Here we describe an approach to generate a potent HDM dual inhibitor, p53LZ2, by rational protein grafting of the p53 transactivation domain onto a homodimeric leucine zipper. p53LZ2 shows tight binding affinity to both HDMs compared with wild-type p53 in vitro. X-ray crystallographic, comparative modelling and small-angle X-ray scattering studies of p53LZ2-HDM complexes show butterfly-shaped structures. A cell-permeable TAT-p53LZ2 effectively inhibits the cancer cell growth in wild-type but not mutant p53 by arresting cell cycle and inducing apoptosis in vitro. Thus, p53LZ2, designed by rational grafting, shows a potential therapeutic approach against cancer. Protein grafting of p53TAD onto a leucine zipper scaffold generates a potent HDM dual inhibitor.,Lee JH, Kang E, Lee J, Kim J, Lee KH, Han J, Kang HY, Ahn S, Oh Y, Shin D, Hur K, Chae SY, Song PH, Kim YI, Park JC, Lee JI Nat Commun. 2014 May 7;5:3814. doi: 10.1038/ncomms4814. PMID:24804811 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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