Inhibition of DNA helicases with DNA-competitive inhibitors.
Helicases form an attractive protein family for drug discovery because they are involved in various human diseases. In this report, we show that it is possible to inhibit both the ATPase and the helicase activities of a DNA helicase with dibenzothiepins that bind at its nucleic acid binding site. These results suggest a drug discovery strategy to inhibit DNA helicases.
Dubaele
Sandy
S
Novartis Institutes for Biomedical Research, Oncology Research, CH-4002 Basel, Switzerland.
Jahnke
Wolfang
W
Schoepfer
Joseph
J
Fuchs
Jean
J
Chène
Patrick
P
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D003988:Dibenzothiepins / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D003988:Dibenzothiepins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C059716:helD protein, E coli; D004265:DNA Helicases