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‘LeishMan’ Topoisomerase I: an Ideal Chimera for Unraveling the Role of the Small Subunit of Unusual bi-subunit Topoisomerase I from Leishmania donovani

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Title ‘LeishMan’ Topoisomerase I: an Ideal Chimera for
Unraveling the Role of the Small Subunit of Unusual
bi-subunit Topoisomerase I from Leishmania donovani
 
Creator Ganguly, Agneyo
Das, Benu Brata
Sen, Nilkantha
Roy, Amit
Bose Dasgupta, Somdeb
Majumder, Hemanta K
 
Subject Infectious Diseases and Immunology
 
Description The active site tyrosine residue of all monomeric
type IB topoisomerases resides in the C-terminal
domain of the enzyme. Leishmania donovani, possesses
unusual heterodimeric type IB topoisomerase.
The small subunit harbors the catalytic
tyrosine within the SKXXY motif. To explore the
functional relationship between the two subunits,
we have replaced the small subunit of L.donovani
topoisomerase I with a C-terminal fragment of
human topoisomerase I (HTOP14). The purified
LdTOP1L (large subunit of L.donovani topoisomerase
I) and HTOP14 were able to reconstitute
topoisomerase I activity when mixed in vitro. This
unusual enzyme, ‘LeishMan’ topoisomerase I (Leish
for Leishmania and Man for human) exhibits less
efficiency in DNA binding and strand passage
compared with LdTOP1L/S. Fusion of LdTOP1L
with HTOP14 yielded a more efficient enzyme with
greater affinity for DNA and faster strand passage
ability. Both the chimeric enzymes are less sensitive
to camptothecin than LdTOP1L/S. Restoration of
topoisomerase I activity by LdTOP1L and HTOP14
suggests that the small subunit of L.donovani
topoisomerase I is primarily required for supplying
the catalytic tyrosine. Moreover, changes in the
enzyme properties due to substitution of LdTOP1S
with HTOP14 indicate that the small subunit contributes
to subunit interaction and catalytic efficiency
of the enzyme
 
Date 2006
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/438/1/NUCLEIC_ACIDS_RESEARCH%2C_34(_21)%2C__6286%2D6297[5].pdf
Ganguly, Agneyo and Das, Benu Brata and Sen, Nilkantha and Roy, Amit and Bose Dasgupta, Somdeb and Majumder, Hemanta K (2006) ‘LeishMan’ Topoisomerase I: an Ideal Chimera for Unraveling the Role of the Small Subunit of Unusual bi-subunit Topoisomerase I from Leishmania donovani. Nucleic Acids Research, 34 (21). pp. 6286-6297.
 
Relation http://dx.doi.org/10.1093/nar/gkl829
http://www.eprints.iicb.res.in/438/