Topostatin, a novel inhibitor of topoisomerases I and II produced by Thermomonospora alba strain No. 1520. III. Inhibitory properties.
A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. The inhibitory activity of topostatin was shown to be pH- and temperature-dependent with a maximum around at pH 6 and 28 degrees C. The stability of topostatin decreased with decreasing pH and rising temperature. Topostatin inhibited topoisomerases I and II in a competitive manner with respect to DNA. The inhibitor also inhibited some restriction endonucleases such as Sca I, Hind III and Pst I, but not Alu I, Bam HI, Eco RI, RNase A, DNase I, DNase II and DNA ligase. Topostatin did not induce the nuclear accumulation of p53 protein by DNA damage in the normal human cells.
Suzuki
K
K
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Yamaizumi
M
M
Tateishi
S
S
Monnai
Y
Y
Uyeda
M
M
D002467:Cell Nucleus / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007769:Lactams / Q000494:pharmacology*; D013696:Temperature; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004791:Enzyme Inhibitors; D007769:Lactams; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; C116935:topostatin; D015252:Deoxyribonucleases, Type II Site-Specific