AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C

Abstract Despite the highly oxidative environment of the phagosomal lumen, the need for maintaining redox homeostasis is a critical aspect of mycobacterial biology. The pathogens are equipped with the sophisticated thioredoxin- (Trx) and peroxiredoxin system, including TrxC and the alkyl hydroperoxi...

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Autores principales:	Chui Fann Wong, Joon Shin, Malathy Sony Subramanian Manimekalai, Wuan Geok Saw, Zhan Yin, Shashi Bhushan, Arvind Kumar, Priya Ragunathan, Gerhard Grüber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/abe170557c194602b72f09980a0259f7
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spelling	oai:doaj.org-article:abe170557c194602b72f09980a0259f72021-12-02T15:06:17ZAhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C10.1038/s41598-017-05354-52045-2322https://doaj.org/article/abe170557c194602b72f09980a0259f72017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05354-5https://doaj.org/toc/2045-2322Abstract Despite the highly oxidative environment of the phagosomal lumen, the need for maintaining redox homeostasis is a critical aspect of mycobacterial biology. The pathogens are equipped with the sophisticated thioredoxin- (Trx) and peroxiredoxin system, including TrxC and the alkyl hydroperoxide reductase subunit C (AhpC), whereby TrxC is one of the reducing partners of AhpC. Here we visualize the redox modulated dodecamer ring formation of AhpC from Mycobacterium bovis (BCG strain; MbAhpC) using electron microscopy and present novel insights into the unique N-terminal epitope (40 residues) of mycobacterial AhpC. Truncations and amino acid substitutions of residues in the unique N-terminus of MbAhpC provide insights into their structural and enzymatic roles, and into the evolutionary divergence of mycobacterial AhpC versus that of other bacteria. These structural details shed light on the epitopes and residues of TrxC which contributes to its interaction with AhpC. Since human cells lack AhpC, the unique N-terminal epitope of mycobacterial AhpC as well as the MbAhpC-TrxC interface represent an ideal drug target.Chui Fann WongJoon ShinMalathy Sony Subramanian ManimekalaiWuan Geok SawZhan YinShashi BhushanArvind KumarPriya RagunathanGerhard GrüberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chui Fann Wong Joon Shin Malathy Sony Subramanian Manimekalai Wuan Geok Saw Zhan Yin Shashi Bhushan Arvind Kumar Priya Ragunathan Gerhard Grüber AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
description	Abstract Despite the highly oxidative environment of the phagosomal lumen, the need for maintaining redox homeostasis is a critical aspect of mycobacterial biology. The pathogens are equipped with the sophisticated thioredoxin- (Trx) and peroxiredoxin system, including TrxC and the alkyl hydroperoxide reductase subunit C (AhpC), whereby TrxC is one of the reducing partners of AhpC. Here we visualize the redox modulated dodecamer ring formation of AhpC from Mycobacterium bovis (BCG strain; MbAhpC) using electron microscopy and present novel insights into the unique N-terminal epitope (40 residues) of mycobacterial AhpC. Truncations and amino acid substitutions of residues in the unique N-terminus of MbAhpC provide insights into their structural and enzymatic roles, and into the evolutionary divergence of mycobacterial AhpC versus that of other bacteria. These structural details shed light on the epitopes and residues of TrxC which contributes to its interaction with AhpC. Since human cells lack AhpC, the unique N-terminal epitope of mycobacterial AhpC as well as the MbAhpC-TrxC interface represent an ideal drug target.
format	article
author	Chui Fann Wong Joon Shin Malathy Sony Subramanian Manimekalai Wuan Geok Saw Zhan Yin Shashi Bhushan Arvind Kumar Priya Ragunathan Gerhard Grüber
author_facet	Chui Fann Wong Joon Shin Malathy Sony Subramanian Manimekalai Wuan Geok Saw Zhan Yin Shashi Bhushan Arvind Kumar Priya Ragunathan Gerhard Grüber
author_sort	Chui Fann Wong
title	AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
title_short	AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
title_full	AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
title_fullStr	AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
title_full_unstemmed	AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C
title_sort	ahpc of the mycobacterial antioxidant defense system and its interaction with its reducing partner thioredoxin-c
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/abe170557c194602b72f09980a0259f7
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AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C

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