Since its original discovery, proliferating cell nuclear antigen (PCNA) has been shown to interact with more than 130 different proteins. However, molecular features that recruit, stabilize, and orient these binding partners upon DNA damage are not clearly understood. Several PCNA interacting proteins (PIPs) contain a conserved sequence motif called a PIP Box. Structural analyses indicate that the binding mode of the PIP Boxes interact at overlapping sites on PCNA suggesting similar affinities. A fluorescence polarization assay that monitors binding of PIP Box peptide mimics to PCNA demonstrated a range of binding affinities. Therefore, it is hypothesized that subtle molecular features in PCNA binding partners may enhance the association with PCNA. This presentation will discuss the features that contribute to an overall favorable interaction between PCNA and its binding partners at the PIP Box interaction site and provide an example of how these features can be translated into small molecule design.

Molecular features that define specific PCNA-protein interactions in DNA repair

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.