Conjugated Eicosapentaenoic Acid Inhibits Human Topoisomerase IB With a Mechanism Different From Camptothecin
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Conjugated Eicosapentaenoic Acid Inhibits Human Topoisomerase IB With a Mechanism Different From Camptothecin
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| Creator |
Castelli, Silvia
Campagna, Alessia Vassallo, Oscar Tesauro, Cinzia Fiorani, Paola Tagliatesta, Pietro Oteri, Francesco Falconi, Mattio Majumder, Hemanta K Desideri, Alessandro |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Conjugated eicosapentaenoic acid (cEPA) has been found to have antitumor effects which has been
ascribed to their ability to inhibit DNA topoisomerases and DNA polymerases. We here show that cEPA
inhibits the catalytic activity of human topoisomerase I, but unlike camptothecin it does not stabilize
the cleavable complex, indicating a different mechanism of action. cEPA inhibits topoisomerase by
impeding the catalytic cleavage of the DNA substrate as demonstrated using specific oligonucleotide substrates,
and prevents the stabilization of the cleavable complex by camptothecin. Preincubation of the
inhibitor with the enzyme is required to obtain complete inhibition. Molecular docking simulations indicate
that the preferred cEPA binding site is proximal to the active site with the carboxylic group strongly
interacting with the positively charged K443 and K587. Taken together the results indicate that cEPA
inhibitor does not prevent DNA binding but inhibits DNA cleavage, binding in a region close to the topoisomerase
active site.
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| Date |
2009
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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/1004/1/33_ABB_2009.pdf
Castelli, Silvia and Campagna, Alessia and Vassallo, Oscar and Tesauro, Cinzia and Fiorani, Paola and Tagliatesta, Pietro and Oteri, Francesco and Falconi, Mattio and Majumder, Hemanta K and Desideri, Alessandro (2009) Conjugated Eicosapentaenoic Acid Inhibits Human Topoisomerase IB With a Mechanism Different From Camptothecin. Archives of Biochemistry and Biophysics, 486 (2). pp. 103-110. |
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| Relation |
http://dx.doi.org/10.1016/j.abb.2009.04.007
http://www.eprints.iicb.res.in/1004/ |
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