scholarly journals Discovery of a Potent Inhibitor of Replication Protein A Protein–Protein Interactions Using a Fragment-Linking Approach

2013 ◽  
Vol 56 (22) ◽  
pp. 9242-9250 ◽  
Author(s):  
Andreas O. Frank ◽  
Michael D. Feldkamp ◽  
J. Phillip Kennedy ◽  
Alex G. Waterson ◽  
Nicholas F. Pelz ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Potent Inhibitor ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Protein Protein Interactions

Abstract 2473: Fragment-based discovery of inhibitors of replication protein A protein-protein interactions.

2013 ◽  
Author(s):  
Alex G. Waterson ◽  
James D. Patrone ◽  
J. Phillip Kennedy ◽  
Nicholas F. Pelz ◽  
Andreas O. Frank ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Protein Protein Interactions

scholarly journals Investigation of the core binding regions of human Werner syndrome and Fanconi anemia group J helicases on replication protein A

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gyuho Yeom ◽  
Jinwoo Kim ◽  
Chin-Ju Park
Keyword(s):  
Fanconi Anemia ◽  
Protein Interactions ◽  
Werner Syndrome ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Dna Helicases ◽  
Binding Regions ◽  
Werner Syndrome Protein ◽  
Anemia Group

Abstract Werner syndrome protein (WRN) and Fanconi anemia group J protein (FANCJ) are human DNA helicases that contribute to genome maintenance. They interact with replication protein A (RPA), and these interactions dramatically enhance the unwinding activities of both helicases. Even though the interplay between these helicases and RPA is particularly important in the chemoresistance pathway of cancer cells, the precise binding regions, interfaces, and properties have not yet been characterized. Here we present systematic NMR analyses and fluorescence polarization anisotropy assays of both helicase-RPA interactions for defining core binding regions and binding affinities. Our results showed that two acidic repeats of human WRN bind to RPA70N and RPA70A. For FANCJ, the acidic-rich sequence in the C-terminal domain is the binding region for RPA70N. Our results suggest that each helicase interaction has unique features, although they both fit an acidic peptide into a basic cleft for RPA binding. Our findings shed light on the protein interactions involved in overcoming the DNA-damaging agents employed in the treatment of cancer and thus potentially provide insight into enhancing the efficacy of cancer therapy.

scholarly journals Recent advancements in the discovery of protein–protein interaction inhibitors of replication protein A

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 259-267 ◽  
Author(s):  
James D. Patrone ◽  
Alex G. Waterson ◽  
Stephen W. Fesik
Keyword(s):  
Dna Damage ◽  
Recent Work ◽  
Dna Damage Response ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein A ◽  
Replication Protein A ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Damage Response

This review summarizes recent work directed toward the discovery of selective inhibitors of the protein–protein interactions between RPA and proteins involved in the initiation of DNA damage response pathways.

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