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

Biochemistry
G H GoldmanL F Liu

Abstract

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 nucle...Continue Reading

References

Nov 12, 1993·Journal of Medicinal Chemistry·Y L JaninE Bisagni
Jun 1, 1996·Bioorganic & Medicinal Chemistry·D MakheyE J LaVoie
Jan 1, 1994·Advances in Pharmacology·J L Nitiss

❮ Previous
Next ❯

Citations

Sep 28, 1998·Biochimica Et Biophysica Acta·Y PommierD Strumberg
Jun 6, 1998·Biochimie·Y Pommier
May 23, 2002·Antimicrobial Agents and Chemotherapy·Shabana I KhanAlice M Clark
Nov 18, 2006·Phytochemistry·Lenka GrycováRadek Marek
Apr 4, 2002·Fungal Genetics and Biology : FG & B·Gustavo H GoldmanSteven D Harris
Dec 3, 1999·Antimicrobial Agents and Chemotherapy·M Del PoetaJ R Perfect

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allergy & Infectious Diseases

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Allergy & Infectious Diseases (ASM)

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.