Functional dissection of the C-terminal domain of type II DNA topoisomerase from the kinetoplastid hemoØagellate Leishmania donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Functional dissection of the C-terminal domain of
type II DNA topoisomerase from the kinetoplastid
hemoØagellate Leishmania donovani
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| Creator |
Sengupta, Tanushri
Mukherjee, Mandira Mandal, Chhabinath Das, Aditi Majumder, Hemanta K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
The amino acid sequences of the C-terminal domain
(CTD) of the type II DNA topoisomerases are divergent
and species speciÆc as compared with the
highly conserved N-terminal and central domains. A
set of C-terminal deletion mutants of Leishmania
donovani topoisomerase II was constructed.
Removal of more than 178 amino acids out of 1236
amino acid residues from the C-terminus inactivates
the enzyme, whereas removal of 118 amino acids or
less has no apparent effect on the ability of the parasite
enzyme to complement a temperature-sensitive
mutation of the Saccharomyces cerevisiae topoisomerase
II gene. Deletion analysis revealed a
potent nuclear localization signal (NLS) within the
amino acid residues 998±1058. Immunomicroscopy
results suggest that the removal of an NLS in the
CTD is likely to contribute to the physiological dysfunction
of these proteins. Modeling of the LdTOP2
based on the crystal structure of the yeast type II
DNA topoisomerase showed that the parasite
protein assumes a structure similar to its yeast
counterpart harboring all the conserved residues in
a structurally similar position. However, a marked
difference in electrostatic potential was found in a
span of 60 amino acid residues (998±1058), which
also do not have any homology with topoisomerase
II sequences. Such signiÆcant differences can be
exploited by the structure-based design of selective
inhibitors using the structure of the Leishmania
enzyme as a template.
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| Date |
2003
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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/549/1/NUCLEIC_ACIDS_RESEARCH%2C31(18)%2C_5305%2D5316[36].pdf
Sengupta, Tanushri and Mukherjee, Mandira and Mandal, Chhabinath and Das, Aditi and Majumder, Hemanta K (2003) Functional dissection of the C-terminal domain of type II DNA topoisomerase from the kinetoplastid hemoØagellate Leishmania donovani. Nucleic Acids Research, 31 (18). pp. 5305-5316. |
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| Relation |
http://dx.doi.org/10.1093/nar/gkg727
http://www.eprints.iicb.res.in/549/ |
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