ATP Independent Type IB Topoisomerase of Leishmania Donovani is Stimulated by ATP: an Insight into the Functional Mechanism
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
ATP Independent Type IB Topoisomerase of
Leishmania Donovani is Stimulated by ATP:
an Insight into the Functional Mechanism
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| Creator |
Sengupta, Souvik
Ganguly, Agneyo Roy, Amit Somdeb, Bose Dasgupta D’Annessa, IIDA Desideri, Alessandro Majumder, Hemanta K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Most type IB topoisomerases do not require ATP
and Mg2+for activity. However, as shown previously
for vaccinia topoisomerase I, we demonstrate that
ATP stimulates the relaxation activity of the unusual
heterodimeric type IB topoisomerase from
Leishmania donovani (LdTOP1L/S) in the absence
of Mg2+. The stimulation is independent of ATP hydrolysis
but requires salt as a co-activator. ATP
binds to LdTOP1L/S and increases its rate of
strand rotation. Docking studies indicate that the
amino acid residues His93, Tyr95, Arg188 and
Arg190 of the large subunit may be involved in
ATP binding. Site directed mutagenesis of these
four residues individually to alanine and subsequent
relaxation assays reveal that the R190A
mutant topoisomerase is unable to exhibit
ATP-mediated stimulation in the absence of Mg2+.
However, the ATP-independent relaxation activities
of all the four mutant enzymes remain unaffected.
Additionally, we provide evidence that ATP binds
LdTOP1L/S and modulates the activity of the otherwise
ATP-independent enzyme. This study
establishes ATP as an activator of LdTOP1L/S in
the absence of Mg2+.
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| Date |
2011
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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/112/1/NUCLEIC_ACIDS_RESEARCH%2C39(8)%2C3295%2D3309%2C2011[69].pdf
Sengupta, Souvik and Ganguly, Agneyo and Roy, Amit and Somdeb, Bose Dasgupta and D’Annessa, IIDA and Desideri, Alessandro and Majumder, Hemanta K (2011) ATP Independent Type IB Topoisomerase of Leishmania Donovani is Stimulated by ATP: an Insight into the Functional Mechanism. Nucleic Acids Research, 39 (8). pp. 3295-3309. |
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| Relation |
http://dx.doi.org/10.1093/nar/gkq1284
http://www.eprints.iicb.res.in/112/ |
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