ATP-independent DNA topoisomerase II as potential drug target in trypanosomes.
Two categories of trypanosomal type II topoisomerases have been isolated from trypanosomes: one is unique since it is able to realize DNA topoisomerization reactions in the absence of ATP, in contrast to the other enzyme and mammalian topoisomerase II. The biochemical properties of ATP-independent topoisomerase II from Trypanosoma cruzi are described in this report. The enzyme can decatenate trypanosome kinetoplast DNA networks, catenate supercoiled DNA molecules, unknot P4 phage DNA, and cleave double-stranded DNA. The enzyme is inhibited by various classes of drugs and is more sensitive than mammalian topoisomerase II. Therefore, trypanosome ATP-independent topoisomerase II provides a potential target for chemotherapy.
Douc-Rasy
S
S
Laboratoire de Pharmacologie Clinique et Moléculaire, Institut Gustave-Roussy, Villejuif, France.
Riou
J F
JF
Ahomadegbe
J C
JC
Riou
G
G
D000255:Adenosine Triphosphate; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000302:isolation & purification; D004279:DNA, Viral / Q000378:metabolism / Q000648:ultrastructure; D015195:Drug Design; D004587:Electrophoresis, Agar Gel; D004611:Ellipticines / Q000494:pharmacology*; D008854:Microscopy, Electron; D013539:Simian virus 40 / Q000235:genetics; D059005:Topoisomerase II Inhibitors; D014349:Trypanosoma cruzi / Q000201:enzymology*
D000470:Alkaloids; D004279:DNA, Viral; D004611:Ellipticines; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; D004250:DNA Topoisomerases, Type II