In contrast with most bacteria which possess two type II topoisomerases (topoisomerase IV and DNA gyrase), Mycobacterium tuberculosis possesses only one, DNA gyrase, which is functionally a hybrid enzyme. Functional differences between the two type IIA topoisomerases are thought to be specified by a CTD (C-terminal DNA-binding domain), which controls DNA recognition. To explore the molecular mechanism responsible for the hybrid functions of the M. tuberculosis DNA gyrase, we conducted a series of sequence analyses and structural and biochemical experiments with the isolated GyrA CTD and the holoenzyme. Although the CTD displayed a global structure similar to that of bona fide GyrA and ParC paralogues, it harbours a second key motif similar in all respects to that of the conserved GyrA-box sequence motif. Biochemical assays showed that the GyrA-box is responsible for DNA supercoiling, whereas the second GyrA-box-l (GyrA-box-like motif) is responsible for the enhanced decatenation activity, suggesting that the mechanistic originality of M. tuberculosis DNA gyrase depends largely on the particular DNA path around the CTD allowed for by the presence of GyrA-box-l. The results of the present study also provide, through phylogenetic exploration of the entire Corynebacterineae suborder, a new and broader insight into the functional diversity of bacterial type IIA topoisomerases.
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Research Article|
October 10 2013
Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA-boxes
Aurélie Bouige;
Aurélie Bouige
1
*UPMC Université Paris 06, ER5, EA 1541, Laboratoire de Bactériologie-Hygiène, 91 bd de l’Hôpital, F 75013 Paris, France
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Amélie Darmon;
Amélie Darmon
1
†Unité de Microbiologie Structurale, Département de Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
‡UMR3528, CNRS, 25 rue du Dr Roux, F 75015 Paris, France
§Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
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Jérémie Piton;
Jérémie Piton
∥UPR9073, CNRS (affiliated with Université Paris Diderot), Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France
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Mélanie Roue;
Mélanie Roue
†Unité de Microbiologie Structurale, Département de Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
‡UMR3528, CNRS, 25 rue du Dr Roux, F 75015 Paris, France
§Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
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Stéphanie Petrella;
Stéphanie Petrella
†Unité de Microbiologie Structurale, Département de Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
‡UMR3528, CNRS, 25 rue du Dr Roux, F 75015 Paris, France
§Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
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Estelle Capton;
Estelle Capton
*UPMC Université Paris 06, ER5, EA 1541, Laboratoire de Bactériologie-Hygiène, 91 bd de l’Hôpital, F 75013 Paris, France
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Patrick Forterre;
Patrick Forterre
¶Unité Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Département de Microbiologie, Institut Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
**UMR 8621, CNRS, Université Paris-Sud, Institut de Génétique et Microbiologie (IGM), 15 rue Georges Clémenceau, F 91405 Orsay, France
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Alexandra Aubry;
*UPMC Université Paris 06, ER5, EA 1541, Laboratoire de Bactériologie-Hygiène, 91 bd de l’Hôpital, F 75013 Paris, France
††AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de Bactériologie-Hygiène, 91 bd de l’Hôpital, F 75013 Paris, France
‡‡Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, 91 bd de l’Hôpital, F 75013 Paris, France
2Correspondence may be addressed to either of these authors (email alexandra.aubry@upmc.fr or mayer@pasteur.fr).
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Claudine Mayer
†Unité de Microbiologie Structurale, Département de Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
‡UMR3528, CNRS, 25 rue du Dr Roux, F 75015 Paris, France
§Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 25 rue du Dr Roux, F 75015 Paris, France
2Correspondence may be addressed to either of these authors (email alexandra.aubry@upmc.fr or mayer@pasteur.fr).
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Publisher: Portland Press Ltd
Received:
March 22 2013
Revision Received:
July 22 2013
Accepted:
July 22 2013
Accepted Manuscript online:
July 22 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 455 (3): 285–294.
Article history
Received:
March 22 2013
Revision Received:
July 22 2013
Accepted:
July 22 2013
Accepted Manuscript online:
July 22 2013
Citation
Aurélie Bouige, Amélie Darmon, Jérémie Piton, Mélanie Roue, Stéphanie Petrella, Estelle Capton, Patrick Forterre, Alexandra Aubry, Claudine Mayer; Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA-boxes. Biochem J 1 November 2013; 455 (3): 285–294. doi: https://doi.org/10.1042/BJ20130430
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