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Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant

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Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant. / Arnò, Barbara; D'Annessa, Ilda; Tesauro, Cinzia; Zuccaro, Laura; Ottaviani, Alessio; Knudsen, Birgitta R.; Fiorani, Paola; Desideri, Alessandro.

I: PLOS ONE, Bind 8, Nr. 7, e68404, 02.07.2013.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Arnò, Barbara ; D'Annessa, Ilda ; Tesauro, Cinzia ; Zuccaro, Laura ; Ottaviani, Alessio ; Knudsen, Birgitta R. ; Fiorani, Paola ; Desideri, Alessandro. / Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant. I: PLOS ONE. 2013 ; Bind 8, Nr. 7.

Bibtex

@article{d03a2a643afb4268b826603585c03a64,
title = "Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant",
abstract = "A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme, but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples a conformational space much larger than the corresponding domain in the human enzyme. The large linker conformational variability is then linked to important functional properties such as an increased religation rate and a low drug reactivity, demonstrating that the linker domain has a crucial role in the modulation of the topoisomerase IB activity.",
author = "Barbara Arn{\`o} and Ilda D'Annessa and Cinzia Tesauro and Laura Zuccaro and Alessio Ottaviani and Knudsen, {Birgitta R.} and Paola Fiorani and Alessandro Desideri",
year = "2013",
month = jul,
day = "2",
doi = "10.1371/journal.pone.0068404",
language = "English",
volume = "8",
journal = "P L o S One",
issn = "1932-6203",
publisher = "public library of science",
number = "7",

}

RIS

TY - JOUR

T1 - Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant

AU - Arnò, Barbara

AU - D'Annessa, Ilda

AU - Tesauro, Cinzia

AU - Zuccaro, Laura

AU - Ottaviani, Alessio

AU - Knudsen, Birgitta R.

AU - Fiorani, Paola

AU - Desideri, Alessandro

PY - 2013/7/2

Y1 - 2013/7/2

N2 - A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme, but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples a conformational space much larger than the corresponding domain in the human enzyme. The large linker conformational variability is then linked to important functional properties such as an increased religation rate and a low drug reactivity, demonstrating that the linker domain has a crucial role in the modulation of the topoisomerase IB activity.

AB - A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme, but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples a conformational space much larger than the corresponding domain in the human enzyme. The large linker conformational variability is then linked to important functional properties such as an increased religation rate and a low drug reactivity, demonstrating that the linker domain has a crucial role in the modulation of the topoisomerase IB activity.

U2 - 10.1371/journal.pone.0068404

DO - 10.1371/journal.pone.0068404

M3 - Journal article

C2 - 23844196

VL - 8

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 7

M1 - e68404

ER -