Topoisomerase I gene mutations at F270 in the large subunit and N184 in the small subunit contribute to the resistance mechanism of the unicellular parasite Leishmania donovani towards 3,3'-diindolylmethane.

Development of Derivatives of 3, 3′-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons

BACKGROUND The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration....

Mitochondria dependent ROS-mediated programmed cell death (PCD) induced by 3,3'-Diindolylmethane (DIM) through Inhibition of FoF1-ATP Synthase in unicellular protozoan parasite Leishmania donovani

An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3'-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme.

DIM (3,3'-di-indolylmethane), an abundant dietary component of cruciferous vegetables, exhibits a wide spectrum of pharmacological properties. In the present study, we show that DIM is a potent inhibitor of Leishmania donovani topoisomerase I with an IC50 of 1.2 microM. Equilibrium dialysis shows that DIM binds strongly to the free enzyme with a binding constant of 9.73x10(-9) M. The binding af...

The involvement of mutation in the serine 83 of quinolone resistant determining regions of the GyrA Gene in resistance to ciprofloxacin in Escherichia coli .

Appearance of bacteria resistant to antibacterial agents puts physicians in trouble and threatens the health of the world. The rapid development of bacterial resistance in Escherichia coli to ciprofloxacin makes difficult the treatment of infectious diseases. So, detection of the locations of possible mutations in gyrase A gene ( gyrA ) in these mutants is very important to determine the mech...

N-terminal region of the large subunit of Leishmania donovani bi-subunit topoisomerase I is involved in DNA relaxation and int

Leishmania donovani topoisomerase I is an unusual bi-subunit enzyme. We have demonstrated earlier that the large and small subunit could be reconstituted in vitro to show topoisomerase I activity. We extend our biochemical study to evaluate the role of the large subunit in topoisomerase activity. The large subunit (LdTOP1L) shows a substantial degree of homology with the core DNA binding domain...