The energetics of the acetylation switch in p53-mediated transcriptional activation.

ABSTRACT: Targeted therapeutic intervention in receptor-ligand interactions of p53-mediated tumor suppression can impact progression of disease, aging, and variation in genetic expression. Here, we conducted a number of molecular simulations, based on structures of p53 in complex with its transcriptional coactivating CBP bromodomain, determined by NMR spectroscopy, to investigate the energetics of the binding complex. Building on the observation that acetylation of K382 in p53 serves as the essential triggering switch for a specific interaction with CBP, we assessed the differential effect of acetylation on binding from simulations of an octapeptide derived from p53 with acetylated and nonacetylated K382 (residues 379-386). Cluster analysis of the simulations shows that acetylation of the free pepti

SUBMITTER: Eichenbaum KD 

PROVIDER: S-EPMC2882964 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature