A Plant Phytotoxin, Solanapyrone A, Is an Inhibitor of DNA Polymerase β and λ

摘要: Abstract Solanapyrone A, a phytotoxin and enzyme inhibitor isolated from fungus (SUT 01B1-2) selectively inhibits the activities of mammalian DNA polymerase β λ (pol λ) in vitro. The IC50 values compound were 30 μm for pol 37 λ. Because are family their three-dimensional structures thought to be highly similar each other, we used analyze biochemical relationship with solanapyrone A. On β, A antagonistically competed both template nucleotide substrate. BIAcore analysis demonstrated that bound N-terminal 8-kDa domain β. This is known bind single-stranded DNA, provide 5′-phosphate recognition gapped cleave sugar-phosphate bond 3′ an intact apurinic/apyrimidinic (AP) site (i.e. AP lyase activity) including 5′-deoxyribose phosphate activity. inhibited DNA-binding activity but did not influence lyase. Based on these results, inhibitory mechanism discussed.