Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site

Structural, enzymatic and cellular target engagement studies reveal the mechanism of action by N -hydroxyurea small molecule inhibitors of the DNA repair enzyme, human flap endonuclease-1 (FEN1) that prevent cleavage of DNA flaps in cancer cells. The structure-specific nuclease human flap endonuclea...

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Vydané v:	Nature chemical biology Ročník 12; číslo 10; s. 815 - 821
Hlavní autori:	Exell, Jack C, Thompson, Mark J, Finger, L David, Shaw, Steven J, Debreczeni, Judit, Ward, Thomas A, McWhirter, Claire, Siöberg, Catrine L B, Molina, Daniel Martinez, Abbott, W Mark, Jones, Clifford D, Nissink, J Willem M, Durant, Stephen T, Grasby, Jane A
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.10.2016 Nature Publishing Group
Predmet:	631/337/1427 631/45/535/1266 631/92/173 631/92/613 Biochemical Engineering Biochemistry Bioorganic Chemistry Catalytic Domain - drug effects Cell Biology Cell Line, Tumor Chemistry Chemistry/Food Science Crystallography Deoxyribonucleic acid DNA DNA damage DNA repair Dose-Response Relationship, Drug Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Enzymes Exploitation Flap Endonucleases - antagonists & inhibitors Flap Endonucleases - chemistry Flap Endonucleases - metabolism Humans Inhibitors Magnesium Metal ions Mode of action Models, Molecular Molecular biology Molecular Structure Structure-Activity Relationship Substrates Temperature
ISSN:	1552-4450, 1552-4469
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