Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1

• Published in: Nucleic acids research Vol. 52; no. 20; pp. 12616 - 12632
• Main Authors: Wever, Mark J A, Scommegna, Francesca R, Egea-Rodriguez, Sara, Dehghani-Tafti, Saba, Brandao-Neto, Jose, Poisson, Jean-François, Helfrich, Iris, Antson, Alfred A, Rodeschini, Vincent, Bax, Ben, Roche, Didier, Sanders, Cyril M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 11.11.2024
• Subjects: Binding Sites; Crystallography, X-Ray; DNA - chemistry; DNA - metabolism; DNA Helicases - antagonists & inhibitors; DNA Helicases - chemistry; DNA Helicases - metabolism; Drug Discovery; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Models, Molecular; Nucleic Acid Enzymes; Protein Binding; Structure-Activity Relationship; Thiazoles - chemistry; Thiazoles - pharmacology

PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystall...