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Abstract:
The tumor suppressor p53 is a major player in cell growth, genomic stability and cell death. Recent in vivo work suggested that bacterial Pseudomonas aeruginosa azurin can enter cancer cells and interact with p53 promoting cell death. Despite being a novel concept to target cancer, there are no thermodynamic details known for the proposed azurin-p53 complex. This project aims to fill this gap by employing biophysical methods in conjunction with purified proteins in vitro to address four aims. We will reveal (1) which p53 domain interacts with azurin, (2) the molecular mechanism by which azurin increases cellular levels of p53, (3) the region on azurin that interacts with p53 and (4) use the acquired information to propose smaller molecules that retain properties of azurin. We have found that azurin binds to the unstructured N-terminal domain of p53 and a small peptide is able to reproduce part of the azurin interaction. We have also assessed how Cu is metabolized inside cells as well has how the crowdedness of the cell milieu affects proteins. We have made several key discoveries that will aid in the development of azurin-based molecules that can be used as new treatments of cancer.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Final rept. 15 Aug 2006-14 Aug 2008 |
| Pages: |
61 |
| Report Date: |
01-Sep-2008 |
| Contract Number: |
W81XWH-06-1-0572 W81XWH0610572 |
| Report Number: |
A715784 |
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