Characterization of the ATPase activity of topoisomerase II from Leishmania donovani and identification of residues conferring resistance to etoposide
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Characterization of the ATPase activity of topoisomerase II from Leishmania
donovani and identification of residues conferring resistance to etoposide
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| Creator |
Sengupta, Tanushri
Mukherjee, Mandira Das, Aditi Mandal, Chhabinath Das, Rakhee Mukherjee, Tanmoy Majumder, Hemanta K |
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| Subject |
Drug Development/Diagnostics & Biotechnology
Infectious Diseases and Immunology |
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| Description |
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.
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| Publisher |
Portland Press
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| Date |
2005
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/303/1/390BIOCHEMICAL_JOURNAL_390_419%2D426;2005[30].pdf
Sengupta, Tanushri and Mukherjee, Mandira and Das, Aditi and Mandal, Chhabinath and Das, Rakhee and Mukherjee, Tanmoy and Majumder, Hemanta K (2005) Characterization of the ATPase activity of topoisomerase II from Leishmania donovani and identification of residues conferring resistance to etoposide. Biochemical Journal, 390. pp. 419-426. ISSN 0264-6021 |
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| Relation |
http://dx.doi.org/10.1042/BJ20042128
http://www.eprints.iicb.res.in/303/ |
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