Please use this identifier to cite or link to this item:
|Title:||Modulators of the p53-MDM2 interaction : search for MDM2 interactors using structural guidance||Authors:||Lin, Jianqing||Keywords:||DRNTU::Science||Issue Date:||2014||Abstract:||The interaction between MDM2 and p53 is essential for several cellular events, including cell growth, DNA repair, cell cycle arrest and apoptosis. So far, p53 is the only known protein that binds to the hydrophobic pocket of MDM2. In this study, we tried to identify other proteins that also interact with the p53-binding domain of MDM2 using structural homology for which we use the CLICK method. CLICK is an algorithm for structure comparison and works in a topology-independent manner. Three key residues (F19, W23 and L26) for the MDM2-p53 binding were extracted from p53 and compared against all the available Protein Data Bank (PDB) structures. 15728 candidates were identified by CLICK. A filtering step was performed to reduce the number of candidates to 216, which were then validated via structural analysis and literature searches. In the end, one potential binding protein of MDM2 was identified: human fidgetin-like protein 1 (FIGNL1) has a C-terminal helix that can potentially bind to the hydrophobic pocket of MDM2. Preliminary MD simulations were performed to test the binding between MDM2 and the C-terminal helix of human FIGNL1; the results indicated a stable binding. Our study succeeded in identifying a potential binding protein of MDM2 while demonstrating the effectiveness of CLICK.||URI:||http://hdl.handle.net/10356/60604||Rights:||Nanyang Technological University||Fulltext Permission:||restricted||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Student Reports (FYP/IA/PA/PI)|
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.