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Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA

Malaria remains as one of the most deadly diseases in developing countries. The Plasmodium causative agents of human malaria such as Plasmodium falciparum possess an organelle, the apicoplast, which is the result of secondary endosymbiosis and retains its own circular DNA. A type II topoisomerase, D...

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Autores principales: Nagano, Soshichiro, Seki, Eiko, Lin, Ting-Yu, Shirouzu, Mikako, Yokoyama, Shigeyuki, Heddle, Jonathan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643928/
https://www.ncbi.nlm.nih.gov/pubmed/26566222
http://dx.doi.org/10.1371/journal.pone.0142313
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author Nagano, Soshichiro
Seki, Eiko
Lin, Ting-Yu
Shirouzu, Mikako
Yokoyama, Shigeyuki
Heddle, Jonathan G.
author_facet Nagano, Soshichiro
Seki, Eiko
Lin, Ting-Yu
Shirouzu, Mikako
Yokoyama, Shigeyuki
Heddle, Jonathan G.
author_sort Nagano, Soshichiro
collection PubMed
description Malaria remains as one of the most deadly diseases in developing countries. The Plasmodium causative agents of human malaria such as Plasmodium falciparum possess an organelle, the apicoplast, which is the result of secondary endosymbiosis and retains its own circular DNA. A type II topoisomerase, DNA gyrase, is present in the apicoplast. In prokaryotes this enzyme is a proven, effective target for antibacterial agents, and its discovery in P. falciparum opens up the prospect of exploiting it as a drug target. Basic characterisation of P. falciparum gyrase is important because there are significant sequence differences between it and the prokaryotic enzyme. However, it has proved difficult to obtain soluble protein. Here we have predicted a new domain boundary in P. falciparum GyrA that corresponds to the C-terminal domain of prokaryotic GyrA and successfully purified it in a soluble form. Biochemical analyses revealed many similarities between the C-terminal domains of GyrA from E. coli and P. falciparum, suggesting that despite its considerably larger size, the malarial protein carries out a similar DNA wrapping function. Removal of a unique Asn-rich region in the P. falciparum protein did not result in a significant change, suggesting it is dispensable for DNA wrapping.
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spelling pubmed-46439282015-11-18 Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA Nagano, Soshichiro Seki, Eiko Lin, Ting-Yu Shirouzu, Mikako Yokoyama, Shigeyuki Heddle, Jonathan G. PLoS One Research Article Malaria remains as one of the most deadly diseases in developing countries. The Plasmodium causative agents of human malaria such as Plasmodium falciparum possess an organelle, the apicoplast, which is the result of secondary endosymbiosis and retains its own circular DNA. A type II topoisomerase, DNA gyrase, is present in the apicoplast. In prokaryotes this enzyme is a proven, effective target for antibacterial agents, and its discovery in P. falciparum opens up the prospect of exploiting it as a drug target. Basic characterisation of P. falciparum gyrase is important because there are significant sequence differences between it and the prokaryotic enzyme. However, it has proved difficult to obtain soluble protein. Here we have predicted a new domain boundary in P. falciparum GyrA that corresponds to the C-terminal domain of prokaryotic GyrA and successfully purified it in a soluble form. Biochemical analyses revealed many similarities between the C-terminal domains of GyrA from E. coli and P. falciparum, suggesting that despite its considerably larger size, the malarial protein carries out a similar DNA wrapping function. Removal of a unique Asn-rich region in the P. falciparum protein did not result in a significant change, suggesting it is dispensable for DNA wrapping. Public Library of Science 2015-11-13 /pmc/articles/PMC4643928/ /pubmed/26566222 http://dx.doi.org/10.1371/journal.pone.0142313 Text en © 2015 Nagano et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nagano, Soshichiro
Seki, Eiko
Lin, Ting-Yu
Shirouzu, Mikako
Yokoyama, Shigeyuki
Heddle, Jonathan G.
Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title_full Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title_fullStr Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title_full_unstemmed Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title_short Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA
title_sort investigating the roles of the c-terminal domain of plasmodium falciparum gyra
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643928/
https://www.ncbi.nlm.nih.gov/pubmed/26566222
http://dx.doi.org/10.1371/journal.pone.0142313
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