Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by bi- and terbenzimidazoles.
Biochemistry
; 36(21): 6488-94, 1997 May 27.
Article
em En
| MEDLINE
| ID: mdl-9174366
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 (Mr) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspergillus nidulans
/
Benzimidazóis
/
DNA Topoisomerases Tipo I
/
Antifúngicos
Limite:
Humans
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos