Purification and characterization of type II DNA topoisomerase from mouse FM3A cells: phosphorylation of topoisomerase II and modification of its activity

Biochemistry ◽  
1990 ◽  
Vol 29 (2) ◽  
pp. 583-590 ◽  
Author(s):  
Masafumi Saijo ◽  
Takemi Enomoto ◽  
Fumio Hanaoka ◽  
Michio Ui
2005 ◽  
Vol 390 (2) ◽  
pp. 419-426 ◽  
Author(s):  
Tanushri Sengupta ◽  
Mandira Mukherjee ◽  
Aditi Das ◽  
Chhabinath Mandal ◽  
Rakhee Das ◽  
...  

We have cloned and expressed the 43 kDa N-terminal domain of Leishmania donovani topoisomerase II. This protein has an intrinsic ATPase activity and obeys Michaelis–Menten kinetics. Cross-linking studies indicate that the N-terminal domain exists as a dimer both in the presence and absence of nucleotides. Etoposide, an effective antitumour drug, traps eukaryotic DNA topoisomerase II in a covalent complex with DNA. In the present study, we report for the first time that etoposide inhibits the ATPase activity of the recombinant N-terminal domain of L. donovani topoisomerase II. We have modelled the structure of this 43 kDa protein and performed molecular docking analysis with the drug. Mutagenesis of critical amino acids in the vicinity of the ligand-binding pocket reveals less efficient inhibition of the ATPase activity of the enzyme by etoposide. Taken together, these results provide an insight for the development of newer therapeutic agents with specific selectivity.


1983 ◽  
Vol 2 (8) ◽  
pp. 1303-1308 ◽  
Author(s):  
P. Benedetti ◽  
M.I. Baldi ◽  
E. Mattoccia ◽  
G.P. Tocchini-Valentini

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