Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by bi- and terbenzimidazoles

Gustavo H. Goldman, Chiang Yu, Hong Yan Wu, Marilyn M. Sanders, Edmond J. La Voie, Leroy-Fong Liu

研究成果: 雜誌貢獻文章同行評審

20 引文 斯高帕斯(Scopus)

摘要

DNA topoisomerase I has been partially purified from Aspergillus nidulans. The purified enzyme is most likely the major nuclear DNA topoisomerase I on the basis of the following findings. (1) Purified DNA topoisomerase I can relax both positively and negatively supercoiled DNA. (2) Neither an energy cofactor nor Mg(II) is required for the relaxation or the cleavage reaction of the enzyme. On the basis of a phosphate-transfer experiment, the Aspergillus topoisomerase I was shown to have a molecular mass (M(r)) of 105 kDa. The differential sensitivity of the human and Aspergillus topoisomerase I was compared using a number of known human DNA topoisomerase I poisons. Like human DNA topoisomerase I, Aspergillus topoisomerase I is highly sensitive to the poisoning activity of camptothecin and a number of bi- and terbenzimidazoles. However, unlike human topoisomerase I, Aspergillus topoisomerase I is completely resistant to monobenzimidazoles, protoberberines (e.g. coralyne), and nitidine. Cytotoxicity studies using yeast expressing human and yeast topoisomerase I cDNAs have also demonstrated a similar differential sensitivity of yeast topoisomerase I to these human topoisomerase I poisons. These results together suggest that the nuclear fungal topoisomerase I may be sufficiently different from its human counterpart to serve as a molecular target for the development of antifungal drugs.

原文英語
頁(從 - 到)6488-6494
頁數7
期刊Biochemistry
36
發行號21
DOIs
出版狀態已發佈 - 五月 27 1997
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry

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